Happening @ Michigan https://events.umich.edu/list/rss RSS Feed for Happening @ Michigan Events at the University of Michigan. BioArtography Virtual Art Fair Sale through July 21! (July 16, 2020 12:00am) https://events.umich.edu/event/75240 75240-19342129@events.umich.edu Event Begins: Thursday, July 16, 2020 12:00am
Location: Off Campus Location
Organized By: BioArtography

BioArtography is having a Virtual Art Fair through July 21! An exciting collection of new images for 2020 will be launched & returning favorites are still available!

Specials will be offered on our website bioartography.com including 15% off and free U.S. shipping on note cards, prints, framed art, gallery wrap canvas and frameless glass!

Follow @bioartography on Twitter , Instagram and Facebook to keep up with all the details!

Proceeds from the sale of this work help support the training of our next generation of researchers!

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Exhibition Mon, 20 Jul 2020 12:13:02 -0400 2020-07-16T00:00:00-04:00 2020-07-16T23:59:00-04:00 Off Campus Location BioArtography Exhibition BioArtography 2020 Collection
BioArtography Virtual Art Fair Sale through July 21! (July 17, 2020 12:00am) https://events.umich.edu/event/75240 75240-19342130@events.umich.edu Event Begins: Friday, July 17, 2020 12:00am
Location: Off Campus Location
Organized By: BioArtography

BioArtography is having a Virtual Art Fair through July 21! An exciting collection of new images for 2020 will be launched & returning favorites are still available!

Specials will be offered on our website bioartography.com including 15% off and free U.S. shipping on note cards, prints, framed art, gallery wrap canvas and frameless glass!

Follow @bioartography on Twitter , Instagram and Facebook to keep up with all the details!

Proceeds from the sale of this work help support the training of our next generation of researchers!

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Exhibition Mon, 20 Jul 2020 12:13:02 -0400 2020-07-17T00:00:00-04:00 2020-07-17T23:59:00-04:00 Off Campus Location BioArtography Exhibition BioArtography 2020 Collection
BioArtography Virtual Art Fair Sale through July 21! (July 18, 2020 12:00am) https://events.umich.edu/event/75240 75240-19342131@events.umich.edu Event Begins: Saturday, July 18, 2020 12:00am
Location: Off Campus Location
Organized By: BioArtography

BioArtography is having a Virtual Art Fair through July 21! An exciting collection of new images for 2020 will be launched & returning favorites are still available!

Specials will be offered on our website bioartography.com including 15% off and free U.S. shipping on note cards, prints, framed art, gallery wrap canvas and frameless glass!

Follow @bioartography on Twitter , Instagram and Facebook to keep up with all the details!

Proceeds from the sale of this work help support the training of our next generation of researchers!

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Exhibition Mon, 20 Jul 2020 12:13:02 -0400 2020-07-18T00:00:00-04:00 2020-07-18T23:59:00-04:00 Off Campus Location BioArtography Exhibition BioArtography 2020 Collection
BioArtography Virtual Art Fair Sale through July 21! (July 19, 2020 12:00am) https://events.umich.edu/event/75240 75240-19342132@events.umich.edu Event Begins: Sunday, July 19, 2020 12:00am
Location: Off Campus Location
Organized By: BioArtography

BioArtography is having a Virtual Art Fair through July 21! An exciting collection of new images for 2020 will be launched & returning favorites are still available!

Specials will be offered on our website bioartography.com including 15% off and free U.S. shipping on note cards, prints, framed art, gallery wrap canvas and frameless glass!

Follow @bioartography on Twitter , Instagram and Facebook to keep up with all the details!

Proceeds from the sale of this work help support the training of our next generation of researchers!

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Exhibition Mon, 20 Jul 2020 12:13:02 -0400 2020-07-19T00:00:00-04:00 2020-07-19T23:59:00-04:00 Off Campus Location BioArtography Exhibition BioArtography 2020 Collection
BioArtography Virtual Art Fair Sale through July 21! (July 20, 2020 12:00am) https://events.umich.edu/event/75240 75240-19379434@events.umich.edu Event Begins: Monday, July 20, 2020 12:00am
Location:
Organized By: BioArtography

BioArtography is having a Virtual Art Fair through July 21! An exciting collection of new images for 2020 will be launched & returning favorites are still available!

Specials will be offered on our website bioartography.com including 15% off and free U.S. shipping on note cards, prints, framed art, gallery wrap canvas and frameless glass!

Follow @bioartography on Twitter , Instagram and Facebook to keep up with all the details!

Proceeds from the sale of this work help support the training of our next generation of researchers!

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Exhibition Mon, 20 Jul 2020 12:13:02 -0400 2020-07-20T00:00:00-04:00 2020-07-20T23:59:00-04:00 BioArtography Exhibition BioArtography 2020 Collection
BioArtography Virtual Art Fair Sale through July 21! (July 21, 2020 12:00am) https://events.umich.edu/event/75240 75240-19379435@events.umich.edu Event Begins: Tuesday, July 21, 2020 12:00am
Location:
Organized By: BioArtography

BioArtography is having a Virtual Art Fair through July 21! An exciting collection of new images for 2020 will be launched & returning favorites are still available!

Specials will be offered on our website bioartography.com including 15% off and free U.S. shipping on note cards, prints, framed art, gallery wrap canvas and frameless glass!

Follow @bioartography on Twitter , Instagram and Facebook to keep up with all the details!

Proceeds from the sale of this work help support the training of our next generation of researchers!

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Exhibition Mon, 20 Jul 2020 12:13:02 -0400 2020-07-21T00:00:00-04:00 2020-07-21T23:59:00-04:00 BioArtography Exhibition BioArtography 2020 Collection
PhD Defense: Benjamin Juliar (July 28, 2020 1:00pm) https://events.umich.edu/event/75205 75205-19330337@events.umich.edu Event Begins: Tuesday, July 28, 2020 1:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via BlueJeans. The link will be placed below.

BlueJeans Link: https://bluejeans.com/358462383

Engineering large viable tissues requires techniques for encouraging rapid capillary bed formation to prevent necrosis. A convenient means of creating this micro-vascular network is through spontaneous neovascularization, which occurs when endothelial cells (ECs) and supportive stromal cells are co-encapsulated within a variety of hydrogel-based extracellular matrices (ECM) and self-assemble into an interconnected network of endothelial tubules. Although this is a robust phenomenon, the environmental and cell-specific determinants that affect the rate and quality of micro-vascular network formation still require additional characterization to improve clinical translatability. This thesis investigates how the proteolytic susceptibility of engineered matrices effects neovascular self-assembly in poly(ethylene glycol) (PEG) hydrogels and provides characterization of changes to matrix mechanics that accompany neovascular morphogenesis in fibrin and PEG hydrogels.

Proteolytic ECM remodeling is essential for the process of capillary morphogenesis. Pharmacological inhibitor studies suggested a role for both matrix metalloproteinases (MMP)- and plasmin-mediated mechanisms of ECM remodeling in an EC-fibroblast co-culture model of vasculogenesis in fibrin. To further investigate the potential contribution of plasmin mediated matrix degradation in facilitating capillary morphogenesis we employed PEG hydrogels engineered with proteolytic specificity to either MMPs, plasmin, or both. Although fibroblasts spread in plasmin-selective hydrogels, we only observed robust capillary morphogenesis in MMP-sensitive matrices, with no added benefit in dual susceptible hydrogels. Enhanced capillary morphogenesis was observed, however, in PEG hydrogels engineered with increased susceptibility to MMPs without altering proteolytic selectivity or hydrogel mechanical properties. These findings highlight the critical importance of MMP-mediated ECM degradation during vasculogenesis and justify the preferential selection of MMP-degradable peptide crosslinkers in the design of synthetic hydrogels used to promote vascularization.

Matrix stiffness is a well-established cue in cellular morphogenesis, however, the converse effect of cellular remodeling on environmental mechanics is comparatively under characterized. In fibrin hydrogels, we applied traditional bulk rheology and laser tweezers-based active microrheology to demonstrate that both ECs and fibroblasts progressively stiffen the ECM across length scales, with the changes in bulk properties dominated by fibroblasts. Despite a lack of fibrillar architecture, a similar stiffening effect was observed in MMP-degradable PEG hydrogels. This stiffening tightly correlated with degree of vessel formation and critically depended on active cellular contractility. To a lesser degree, deposition of ECM proteins also appeared to contribute to progressive hydrogel stiffening. Blocking cell-mediated hydrogel degradation abolished stiffening, demonstrating that matrix metalloproteinase (MMP)-mediated remodeling is required for stiffening to occur. EC co-culture with mesenchymal stem cells (MSCs) in PEG resulted in reduced vessel formation compared to fibroblast co-cultures and no change in hydrogel mechanics over time. The correlation between matrix stiffening and enhanced vessel formation, and dependence on cellular contractility, suggests differences in vessel formation between fibroblasts and MSCs may be partially mediated by differences in cellular contractility. Collectively, these findings provide a deeper understanding of mechanobiological effects during capillary morphogenesis and highlight the dynamic reciprocity between cells and their mechanical environment.

Chair: Dr. Andrew Putnam

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Lecture / Discussion Tue, 14 Jul 2020 11:02:36 -0400 2020-07-28T13:00:00-04:00 2020-07-28T14:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Katy Norman (July 30, 2020 10:00am) https://events.umich.edu/event/75267 75267-19395124@events.umich.edu Event Begins: Thursday, July 30, 2020 10:00am
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via BlueJeans. The link will be posted below.

BlueJeans: https://bluejeans.com/516255948

Mucosal surfaces in the lung interface with the outside environment for breathing purposes, but also provide the first line of defense against invading pathogens. The intricate balance of effective immune protection at the pulmonary epithelium without problematic inflammation is not well understood, but is an important consideration in complex lung diseases such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Although IPF is a fibrotic interstitial lung disease of unknown origin and COPD is an obstructive lung disease, they do share some similarities. Both are heterogeneous and progressive in nature, have no cure and few treatment options, advance through unknown mechanisms, and involve an aberrant immune response. As research has focused into the role the immune system plays in IPF and COPD, it has become clear that disease progression is caused by a complex dysregulation of immune factors and cells across the tissue compartments of the lungs and blood.

Data-driven modeling approaches offer the opportunity to infer protein interaction networks, which are able to identify diagnostic and prognostic biomarkers and also serve as the basis for new insight into systems-level mechanisms that define a disease state. Additionally, these approaches are able to integrate data from across multiple tissue compartments, allowing for a more holistic picture of a disease to be formed. Here, we have applied data-driven modeling approaches including partial least squares discriminant analysis, principal component analysis, decision tree analysis, and hierarchical clustering to high-throughput cell and cytokine measurements from human blood and lung samples to gain systems-level insight into IPF and COPD.

Overall we found that these approaches were useful for identifying signatures of proteins that differentiated disease state and progression better than current classifiers. We also found that integrating protein and cell measurements across tissue compartments generally improved classification and was useful for generating new mechanistic insight into progression and exacerbation events. In evaluating IPF progression, we showed that the blood proteome of progressors, but not of non-progressors, changes over time, and that our data-driven modeling techniques were able to capture these changes. Curiously, our models showed that complement system components may be associated with both COPD and IPF disease progression. Lastly, though our analysis suggested that circulating blood cytokines were not useful for differentiating disease state or progression, preliminary work suggested that cell-cell communication networks arising from stimulated peripheral blood proteins may be more useful for classification and gaining mechanistic insight from minimally invasive blood samples. Overall, we believe that this approach will be useful for studying the mucosal immune response present in other diseases that are also progressive or heterogeneous in nature.

Chair: Dr. Kelly Arnold

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Lecture / Discussion Wed, 22 Jul 2020 16:19:44 -0400 2020-07-30T10:00:00-04:00 2020-07-30T11:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Josiah Simeth (August 5, 2020 2:00pm) https://events.umich.edu/event/75278 75278-19402991@events.umich.edu Event Begins: Wednesday, August 5, 2020 2:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Notice: This event will be held via BlueJeans. The link will be placed below.

BlueJeans: https://bluejeans.com/715371816

Measures of regional and global liver function are critical in guiding treatments for intrahepatic cancers, and liver function is a dominant factor in the survival of patients with hepatocellular carcinoma (HCC). Global and regional liver function assessments are important for defining the magnitude and spatial distribution of radiation dose to preserve functional liver parenchyma and reduce incidence of hepatotoxicity from radiation therapy (RT) for intrahepatic cancer treatment. This individualized liver function-guided RT strategy is critical for patients with heterogeneous and poor liver function, often observed in cirrhotic patients treated for HCC. Dynamic gadoxetic-acid enhanced (DGAE) magnetic resonance imaging (MRI) allows investigation of liver function through observation of the uptake of contrast agent into the hepatocytes.

This work seeks to determine if gadoxetic uptake rate can be used as a reliable measure of liver function, and to develop robust methods for uptake estimation with an interest in the therapeutic application of this knowledge in the case of intrahepatic cancers. Since voxel-by voxel fitting of the preexisting nonlinear dual-input two-compartment model is highly susceptible to over fitting, and highly dependent on data that is both temporally very well characterized and low in noise, this work proposes and validates a new model for quantifying the voxel-wise uptake rate of gadoxetic acid as a measure of regional liver function. This linearized single-input two-compartment (LSITC) model is a linearization of the pre-existing dual-input model but is designed to perform uptake quantification in a more robust, computationally simpler, and much faster manner. The method is validated against the preexisting dual-input model for both real and simulated data. Simulations are used to investigate the effects of noise as well as issues related to the sampling of the arterial peak in the characteristic input functions of DGAE MRI.

Further validation explores the relationship between gadoxetic acid uptake rate and two well established global measures of liver function, namely: Indocyanine Green retention (ICGR) and Albumin-Bilirubin (ALBI) score. This work also establishes the relationships between these scores and imaging derived measures of whole liver function using uptake rate. Additionally, the same comparisons are performed for portal venous perfusion, a pharmacokinetic parameter that has been observed to correlate with function, and has been used as a guide for individualized liver function-guided RT. For the patients assessed, gadoxetic acid uptake rate performs significantly better as a predictor of whole liver function than portal venous perfusion.
This work also investigates the possible gains that could be introduced through use of gadoxetic uptake rate maps in the creation of function-guided RT plans. To this end, plans were created using both perfusion and uptake, and both were compared to plans that did not use functional guidance. While the plans were generally broadly similar, significant differences were observed in patients with severely compromised uptake that did not correspond with compromised perfusion.

This dissertation also deals with the problem of quantifying uptake rate in suboptimal very temporally sparse or short DGAE MRI acquisitions. In addition to testing the limits of the LSITC model for these limited datasets (both realistic and extreme), a neural network-based approach to quantification of uptake rate is developed, allowing for increased robustness over current models.

Chair: Dr. Yue Cao

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Lecture / Discussion Thu, 23 Jul 2020 17:51:41 -0400 2020-08-05T14:00:00-04:00 2020-08-05T15:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Ziwen Zhu (August 26, 2020 9:30am) https://events.umich.edu/event/75720 75720-19576537@events.umich.edu Event Begins: Wednesday, August 26, 2020 9:30am
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via Zoom. The link will be placed below.

Zoom: umich.zoom.us/j/92149340369

Branched Chain amino acids (BCAAs) play an essential role in cell metabolism supplying both carbon and nitrogen in pancreatic cancers, and their increased levels have been associated with increased risk of pancreatic ductal adenocarcinomas (PDACs). It remains unclear how stromal cells regulate BCAA metabolism in PDAC cells and how mutualistic determinants control BCAA metabolism in the tumor milieu. In chapter 1, we present an overview of PDAC biology, tumor microenvironment (TME), altered cancer metabolism and BCAA metabolism. In chapter 2, we uncover differential gene expression of enzymes involved in BCAA metabolism accompanied by distinct catabolic, oxidative, and protein turnover fluxes between cancer-associated fibroblasts (CAFs) and cancer cells with a marked branched-chain keto acids (BCKA)-addiction in PDAC cells. In chapter 3, we showed that cancer-induced stromal reprogramming fuels this BCKA-addiction. We then show the functions of BCAT2 and DBT in the PDAC cells in chapters 3 and 4. We identify BCAT1 as the BCKA regulator in CAFs in chapter 5. In chapter 6, we dictated the internalization of the extracellular matrix from the tumor microenvironment to supply amino acid precursors for BCKA secretion by CAFs. We also showed that the TGF-β/SMAD5 axis directly targets BCAT1 in CAFs in chapter 7. In chapter 8, we validate the in vitro results in human patient-derived circulating tumor cells (CTCs) model. Furthermore, the same results were also validated in PDAC tissue slices, which recapitulate tumor heterogeneity and mimic the in vivo microenvironment in chapter 9. We conclude this manuscript with chapter 10 in which we propose future studies and present directions towards pancreatic cancer research. In summary, our findings reveal therapeutically actionable targets in stromal and cancer cells to regulate the symbiotic BCAA coupling among the cellular constituents of the PDAC microenvironment.

Chair: Dr. Deepak Nagrath

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Lecture / Discussion Fri, 14 Aug 2020 12:02:15 -0400 2020-08-26T09:30:00-04:00 2020-08-26T10:30:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
RNA Collaborative Seminar featuring: Sue Hammoud, Human Genetics & Justin Colacino, Environmental Health Sciences (September 9, 2020 4:00pm) https://events.umich.edu/event/75865 75865-19615931@events.umich.edu Event Begins: Wednesday, September 9, 2020 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

ZOOM REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_GjVNcoWtRG6OkzxSDmfb8A

"Same Same Different: Single cell RNAseq identifies conserved and divergent features of mammalian spermatogenesis"
Sue Hammoud, Ph.D.
Assistant Professor of Human Genetics
Website: https://hammoud.lab.medicine.umich.edu/

~and~

"Single cell transcriptomic profiling to understand breast stem cell heterogeneity in development and cancer disparities"
Justin Colacino. Ph.D.
Assistant Professor of Environmental Health Sciences
Website: https://www.colacinolab.com/

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Lecture / Discussion Wed, 26 Aug 2020 11:44:32 -0400 2020-09-09T16:00:00-04:00 2020-09-09T17:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion RNA Collaborative
Identifying Emergency Funds and How to Advocate for Making Room in Your Financial Aid Package (September 11, 2020 2:00pm) https://events.umich.edu/event/75507 75507-19513173@events.umich.edu Event Begins: Friday, September 11, 2020 2:00pm
Location: Off Campus Location
Organized By: CEW+

Advance registration is required; look for the Zoom link at the bottom of your confirmation email after registering.

This session will provide information about how you can seek emergency funds should you experience an emergency situation or one-time, unusual, unforeseen expense while in school. Information about the types of situations that qualify for emergency funds and where to seek funding will be covered during this presentation.

RSVP HERE: http://www.cew.umich.edu/events/identifying-emergency-funds-and-how-to-advocate-for-making-room-in-your-financial-aid-package

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Livestream / Virtual Tue, 18 Aug 2020 14:02:34 -0400 2020-09-11T14:00:00-04:00 2020-09-11T15:00:00-04:00 Off Campus Location CEW+ Livestream / Virtual A jar of spilled change
RNA Seminar featuring: Andrey Krasilnikov, Penn State (September 21, 2020 4:00pm) https://events.umich.edu/event/75802 75802-19608017@events.umich.edu Event Begins: Monday, September 21, 2020 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

ZOOM REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_obckKUCLT4mXI7kPskzc-Q

KEYWORDS: Ribozymes, RNase P, RNase MRP, ribonucleoprotein complexes, RNA-driven protein remodelling

ABSTRACT: Ribonuclease (RNase) P is a ribozyme-based catalytic ribonucleoprotein complex involved primarily in the maturation of tRNA in all three domains of life. In the course of evolution, the size and complexity of RNase P grew as the catalytic RNA moiety recruited additional protein components. In eukaryotes, the RNase P lineage has split, giving rise to a related RNP enzyme called RNase MRP, which shares multiple structural features (including most of the protein components) with the eukaryotic RNase P, but has a distinct and non-overlapping specificity. We report the recently solved cryo-EM structure of the 450 kDa yeast RNase MRP holoenzyme and compare it with the structure of its progenitor RNP, RNase P. We show that, surprisingly, several of the proteins shared by RNase MRP and RNase P undergo RNA-driven structural remodeling, allowing the same proteins to function in distinct structural contexts. This remodeling, combined with altered peripheral RNA elements, results in the functional diversification of the two closely related RNPs, in spite of the structural conservation of the nearly identical catalytic cores, demonstrating structural underpinnings of the acquisition of new functions by catalytic RNPs.

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Lecture / Discussion Thu, 17 Sep 2020 07:12:03 -0400 2020-09-21T16:00:00-04:00 2020-09-21T17:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Andrey Krasilnikov, Penn State
RNA Seminar featuring: Hiroaki Suga, University of Tokyo (September 28, 2020 9:00am) https://events.umich.edu/event/75805 75805-19608020@events.umich.edu Event Begins: Monday, September 28, 2020 9:00am
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

ZOOM REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_PBHPayAvR8WobaSf3z0AUA

ABSTRACT: Macrocyclic peptides possess a number of pharmacological characteristics distinct from other well-established therapeutic molecular classes, resulting in a versatile drug modality with a unique profile of advantages. Macrocyclic peptides are accessible by not only chemical synthesis but also ribosomal synthesis. Particularly, recent inventions of the genetic code reprogramming integrated with an in vitro display format, referred to as RaPID (Random non-standard Peptides Integrated Discovery) system, have enabled us to screen mass libraries (>1 trillion members) of non-standard peptides containing multiple non-proteinogenic amino acids, giving unique properties of peptides distinct from conventional peptides, e.g. greater proteolytic stability, higher affinity (low nM to sub nM dissociation constants similar to antibodies), and superior pharmacokinetics. The field is rapidly growing evidenced by increasing interests from industrial sectors, including small start-ups as well as mega-pharmas, toward drug development efforts on macrocyclic peptides, which has led to several de novo discovered peptides entering clinical trials. This lecture discusses the aforementioned screening technology involving the method of “genetic code reprogramming” powered by flexizymes, and several showcases of therapeutic potentials of macrocyclic peptides.

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Lecture / Discussion Sun, 20 Sep 2020 13:22:07 -0400 2020-09-28T09:00:00-04:00 2020-09-28T10:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Hiroaki Suga, University of Tokyo
Bioethics Discussion: Artificial Intelligence (September 29, 2020 7:00pm) https://events.umich.edu/event/58828 58828-14563719@events.umich.edu Event Begins: Tuesday, September 29, 2020 7:00pm
Location: Lurie Biomedical Engineering
Organized By: The Bioethics Discussion Group

A discussion on how we know machines know.

Here are a few readings to consider:
––Ethical Issues of Artificial Intelligence in Medicine
––Regulatory responses to medical machine learning
––Will artificial intelligence solve the human resource crisis in healthcare?
––Medical ethics considerations on artificial intelligence

For more information and/or to receive a copy of the readings visit http://belmont.bme.umich.edu/bioethics-discussion-group/discussions/047-artificial-intelligence/.

––

While people are still allowed on campus, discussions will be held on the front lawn of Lurie Biomedical Engineering building. Participants will be asked to enter the area via a “welcome desk” where there will be hand sanitizer, wipes, etc. Participants will be masked, at least 12 feet from one another, and speaking through megaphones with one another. In accordance with public health mandates and guidance, participation will be limited to 20 individuals who sign up to participate ahead of time.

Sign up here: https://belmont.bme.umich.edu/ask-your-questions-to-ponder/

––
One's intelligence might be artificially enhanced by the blog: https://belmont.bme.umich.edu/incidental-art/

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Lecture / Discussion Tue, 25 Aug 2020 11:09:51 -0400 2020-09-29T19:00:00-04:00 2020-09-29T20:30:00-04:00 Lurie Biomedical Engineering The Bioethics Discussion Group Lecture / Discussion Artificial Intelligence
RNA Seminar featuring: Chase Weidmann, Washington University School of Medicine in St. Louis (October 5, 2020 4:00pm) https://events.umich.edu/event/76147 76147-19665691@events.umich.edu Event Begins: Monday, October 5, 2020 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

ZOOM REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_y9HTFl5RSOSJTJ5qtlhVcw

Keywords: mRNA regulation, noncoding RNA, RNA Structure, RNP granules

Abstract:
Chase Weidmann, Ph.D. has contributed broadly to the field of RNA Biology during his career, studying mechanisms of codon bias during translation, post-transcriptional regulation of mRNAs by RNA-binding proteins, the folding of long non-coding RNAs, and how RNA-protein interaction networks contribute to the function and assembly of functional RNP particles. Chase developed a chemical probing strategy and next-gen sequencing technology, called RNP-MaP, that maps the location of and cooperation between multi-protein networks on RNAs in live cells. Going forward, Chase is interested in understanding how alterations in RNA-binding protein profiles, a cell’s “RBPome”, confer deleterious activities onto noncoding RNAs in human disease, especially in cancer. To further empower this work and his future research program, Chase is now generating and integrating protein mass spectrometry data into his RBPome projects.

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Lecture / Discussion Wed, 16 Sep 2020 09:01:52 -0400 2020-10-05T16:00:00-04:00 2020-10-05T17:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion photo
Complex Systems Seminar | A Simple Model for a Complex System: Legged Locomotion as an Oscillator (October 6, 2020 11:30am) https://events.umich.edu/event/77060 77060-19790568@events.umich.edu Event Begins: Tuesday, October 6, 2020 11:30am
Location: Off Campus Location
Organized By: The Center for the Study of Complex Systems

VIRTUAL SEMINAR LINK: myumi.ch/v2ZYv

The neuromechanical control and dynamics of legged locomotion are of great interest for biomedical and robotics applications, as well as being an aspect of functional morphology with large ecological implications. Most biomechanists take a "reductionist" approach that attempts to model animal motion by modeling the parts of the organism and their interconnections, thereby combining them into what are sometimes staggeringly complex models. We will discuss a complementary "essentialist" approach, where multi-legged locomotion is viewed as a limit cycle oscillation comprising the body, nervous system, and environment. Through a combination of theoretical mathematical advances, new numerical algorithms, and experimental work on both animals and robots, this approach has revealed new ways to non-invasively inspect neuromechanical feedback pathways, control and coordinate legs, and model complex multi-contact collisions. Talk will be non-technical and suitable for a broad sciences audience.

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Livestream / Virtual Wed, 30 Sep 2020 11:43:45 -0400 2020-10-06T11:30:00-04:00 2020-10-06T13:00:00-04:00 Off Campus Location The Center for the Study of Complex Systems Livestream / Virtual Headshot Shai Revzen
Bioethics Discussion: Artificial Parts (October 13, 2020 5:00pm) https://events.umich.edu/event/58829 58829-14563720@events.umich.edu Event Begins: Tuesday, October 13, 2020 5:00pm
Location: Lurie Biomedical Engineering
Organized By: The Bioethics Discussion Group

A discussion on what is replaceable.

For the discussion, consider a few readings:
––Implant ethics
––Neuro-Prosthetics, the Extended Mind, and Respect for Persons with Disability
––Why Not Artificial Wombs?
––Going Out on a Limb: Prosthetics, Normalcy and Disputing the Therapy/Enhancement Distinction

For more information and/or to receive a copy of the readings visit http://belmont.bme.umich.edu/bioethics-discussion-group/discussions/048-artificial-parts/.

––

While people are still allowed on campus, discussions will be held on the front lawn of Lurie Biomedical Engineering building. Participants will be asked to enter the area via a “welcome desk” where there will be hand sanitizer, wipes, etc. Participants will be masked, at least 12 feet from one another, and speaking through megaphones with one another. In accordance with public health mandates and guidance, participation will be limited to 20 individuals who sign up to participate ahead of time.

Sign up here: https://belmont.bme.umich.edu/ask-your-questions-to-ponder/

––
Part way between "the real" and "the artificial", "the blog": https://belmont.bme.umich.edu/incidental-art/

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Lecture / Discussion Mon, 12 Oct 2020 20:42:47 -0400 2020-10-13T17:00:00-04:00 2020-10-13T18:30:00-04:00 Lurie Biomedical Engineering The Bioethics Discussion Group Lecture / Discussion Artificial Parts
RNA Seminar featuring: Gene Yeo, University of California, San Diego (October 19, 2020 4:00pm) https://events.umich.edu/event/75807 75807-19608023@events.umich.edu Event Begins: Monday, October 19, 2020 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

ZOOM REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_CcI2trSATJy47aGtwrzhew

Abstract: The life-cycle of RNA from transcription to translational regulation is mediated by a diverse (>2000) set of proteins called RNA binding proteins. My lab studies the many roles that RNA binding proteins have in affecting RNA expression, splicing, transport and translation. Through our studies on RNA processing, we have introduced therapeutic strategies to treat neurodegenerative and muscular diseases, built cellular models of neurodevelopmental and neurodegenerative diseases and developed experimental and computational tools that enable the community to probe RNA binding protein-RNA interactions at scale. I will discuss (1) our established and new technologies to identify RNA targets of human RBPs at scale, (2) systematic assays to assign molecular roles to RBPs and (2) functional screens to identify RBPs implicated in cancer / RNA granule formation.

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Lecture / Discussion Wed, 16 Sep 2020 09:57:16 -0400 2020-10-19T16:00:00-04:00 2020-10-19T17:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Gene Yeo, University of California, San Diego
RNA Seminar featuring: Aleksandra Filipovska, University of Western Australia (October 26, 2020 9:00am) https://events.umich.edu/event/75809 75809-19608025@events.umich.edu Event Begins: Monday, October 26, 2020 9:00am
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

ZOOM REGISTRATION REQUIRED:https://umich.zoom.us/webinar/register/WN_f8wC8rrJQzuhYzTEXoW69Q

ABSTRACT:Mitochondria produce more than 90% of the energy required by our bodies and thereby have a fundamental role in cell and energy metabolism. Mitochondria are composed of proteins encoded by both the nuclear and mitochondrial genomes and the coordinated expression of both genomes is essential for energy production. Impaired energy production leads to mitochondrial dysfunction that causes or contributes significantly to a variety of diseases including metabolic disorders and cardiovascular diseases. Mitochondrial dysfunction is caused by mutations in nuclear or mitochondrial genes that encode proteins or regulatory RNAs essential for mitochondrial biogenesis. How uncoordinated gene expression causes mitochondrial dysfunction and compromised energy production in heart and metabolic diseases is poorly understood, making it difficult to develop effective treatments. To unravel how mitochondrial function fails and to identify therapeutic targets it is necessary (i) to understand how gene expression is regulated between mitochondria and the nucleus and (ii) how this regulation is disrupted in disease. We have created new and unique models of metabolic and cardiovascular diseases caused by mutations or loss of nuclear encoded RNA-binding proteins (RBPs) that regulate mitochondrial RNA metabolism and protein synthesis. These new models have identified that energy dysfunction can differentially affect specific organs such as the heart or liver, or multiple organs leading to heart failure or metabolic diseases that can be devastating, such as mitochondrial diseases, or may be as common as insulin resistance and obesity. I will discuss the mechanisms behind these diverse pathologies caused by impaired gene expression and energy dysfunction in heart and metabolic disease.

KEYWORDS: mitochondria, RNA, ribosomes, translation

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Lecture / Discussion Tue, 20 Oct 2020 14:16:54 -0400 2020-10-26T09:00:00-04:00 2020-10-26T10:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion photo
BME PhD Defense: Zhonghua (Aileen) Ouyang (November 6, 2020 10:00am) https://events.umich.edu/event/78398 78398-20022735@events.umich.edu Event Begins: Friday, November 6, 2020 10:00am
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via Zoom. The link will be provided below.

Zoom: https://umich-health.zoom.us/j/94734899583?pwd=MDNEMjE3QU5xVGgwZzNQajE4UlJQUT09

Overactive bladder (OAB) is a highly prevalent condition which negatively affects the physical and mental health of millions of people worldwide. Sacral neuromodulation (SNM), currently serving ~300,000 patients worldwide, is a promising third-line therapy that provides improved efficacy and minimum adherence issue compared to conventional treatments. While current SNM is delivered in an open-loop fashion, the therapy could have improved clinical efficacy by adopting a closed-loop stimulation paradigm that uses objective physiological feedback. Therefore, this dissertation work focuses on using sacral level dorsal root ganglia neural signals to provide sensory feedback for adaptive SNM a feline model.

This work began with exploring machine learning algorithms and feature selection methods for bladder pressure decoding. A Kalman filter delivered the highest performance based on correlation coefficient between the pressure measurements and algorithm estimation. Additionally, firing rate normalization significantly contributed to lowering the normalized error, and a correlation coefficient-based channel selection method provided the lowest error compared to other channel selection methods.

Following algorithm optimization, this work implemented the optimized algorithm and feature selection method in real-time in anesthetized healthy and simulated OAB feline models. A 0.88 ± 0.16 correlation coefficient fit was achieved by the decoding algorithm across 35 normal and simulated OAB bladder fills in five experiments. Closed-loop neuromodulation was demonstrated using the estimated pressure to trigger pudendal nerve stimulation, which increased bladder capacity by 40% in two trials.

Finally, closed-loop SNM stimulation with DRG sensory feedback was performed in a series of anesthetized experiments. It increased bladder capacity by 13.8% over no stimulation (p < 0.001). While there was no statistical difference in bladder capacity between closed-loop and continuous stimulation (p = 0.80), closed-loop stimulation reduced stimulation time by 57.7%. Interestingly, bladder single units had a reduced sensitivity during stimulation, suggesting a potential mechanism of SNM.

Overall, this work demonstrated that sacral level DRG are a viable sensory feedback target for adaptive SNM. Validation in awake and chronic experiments is a crucial step prior to clinical translation of this method.

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Lecture / Discussion Fri, 09 Oct 2020 22:08:12 -0400 2020-11-06T10:00:00-05:00 2020-11-06T11:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
Challenges in dynamic mode decomposition (November 10, 2020 11:30am) https://events.umich.edu/event/79207 79207-20231448@events.umich.edu Event Begins: Tuesday, November 10, 2020 11:30am
Location: Off Campus Location
Organized By: Michigan Institute for Data Science

Dynamic Mode Decomposition (DMD) is a powerful tool in extracting spatio-temporal patterns from multi-dimensional time series. DMD takes in time series data and computes eigenvalues and eigenvectors of a finite-dimensional linear model that approximates the infinite-dimensional Koopman operator which encodes the dynamics. DMD is used successfully in many fields: fluid mechanics, robotics, neuroscience, and more. Two of the main challenges remaining in DMD research are noise sensitivity and issues related to Krylov space closure when modeling nonlinear systems. In our work, we encountered great difficulty in reconstructing time series from multilegged robot data. These are oscillatory systems with slow transients, which decay only slightly faster than a period.
Here we present an investigation of possible sources of difficulty by studying a class of systems with linear latent dynamics which are observed via multinomial observables. We explore the influences of dataset metrics, the spectrum of the latent dynamics, the normality of the system matrix, and the geometry of the dynamics. Our numerical models include system and measurement noise. Our results show that even for these very mildly nonlinear conditions, DMD methods often fail to recover the spectrum and can have poor predictive ability. We show that for a system with a well-posed system matrix, having a dataset with more initial conditions and shorter trajectories can significantly improve the prediction. With a slightly ill-conditioned system matrix, a moderate trajectory length improves the spectrum recovery. Our work provides a self-contained framework on analyzing noise and nonlinearity, and gives generalizable insights dataset properties for DMD analysis.
Work was funded by ARO MURI W911NF-17-1-0306 and the Kahn Foundation.

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Presentation Thu, 05 Nov 2020 10:02:20 -0500 2020-11-10T11:30:00-05:00 2020-11-10T11:50:00-05:00 Off Campus Location Michigan Institute for Data Science Presentation Ziyou Wu
Bioethics Discussion: Democracy (November 10, 2020 5:00pm) https://events.umich.edu/event/58831 58831-14563723@events.umich.edu Event Begins: Tuesday, November 10, 2020 5:00pm
Location: Lurie Biomedical Engineering
Organized By: The Bioethics Discussion Group

A discussion we will choose to have.

A few readings to consider on the matter:
––Bioethics and Democracy
––Bioethics and Populism: How Should Our Field Respond?
––Crowdsourcing in medical research: concepts and applications
––How Democracy Can Inform Consent: Cases of the Internet and Bioethics

For more information and/or to receive a copy of the readings visit http://belmont.bme.umich.edu/bioethics-discussion-group/discussions/050-democracy/.

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While people are still allowed on campus, discussions will be held on the front lawn of Lurie Biomedical Engineering building. Participants will be asked to enter the area via a “welcome desk” where there will be hand sanitizer, wipes, etc. Participants will be masked, at least 12 feet from one another, and speaking through megaphones with one another. In accordance with public health mandates and guidance, participation will be limited to 20 individuals who sign up to participate ahead of time.

Sign up here: https://belmont.bme.umich.edu/ask-your-questions-to-ponder/

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Together, we can read the blog (and probably do much more than that): https://belmont.bme.umich.edu/incidental-art/

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Lecture / Discussion Tue, 10 Nov 2020 16:24:01 -0500 2020-11-10T17:00:00-05:00 2020-11-10T18:30:00-05:00 Lurie Biomedical Engineering The Bioethics Discussion Group Lecture / Discussion Image 050. Democracy
RNA Seminar featuring: Michelle Hastings, Professor, Rosalind Franklin University of Medicine and Science (November 16, 2020 4:00pm) https://events.umich.edu/event/75868 75868-19615934@events.umich.edu Event Begins: Monday, November 16, 2020 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

https://umich.zoom.us/webinar/register/WN_VWX5SY6lSiaNyh5Weh8cHw

Michelle L. Hastings, PhD
Professor, Cell Biology and Anatomy
Director, Center for Genetic Diseases
Rosalind Franklin University of Medicine and Science

ABSTRACT: Antisense oligonucleotides (ASOs) have proven to be an effective therapeutic platform for the treatment of disease. These short, single-stranded, modified nucleotides function by base-pairing with the complementary sequence of an RNA and modulating gene expression in a manner that is dependent on the ASO design and targeting site. We have used ASOs to normalize aberrant gene expression associated with a number of diseases of the nervous system including Alzheimer’s and Parkinson’s disease and Usher syndrome. One of our approaches is under development for the treatment of CLN3 Batten disease, a fatal, pediatric lysosomal storage disease caused by mutations in a gene encoding the lysosomal membrane protein CLN3. The most common mutation associated with CLN3 Batten is a deletion of exons 7 and 8 (CLN3Δex78), which disrupts the mRNA open reading frame by creating a premature termination codon that results in the production of a truncated protein. We devised a therapeutic strategy for treating CLN3 Batten Disease using an ASO that basepairs to CLN3 pre-mRNA and alters splicing to correct the open reading frame of the mutated transcript. Treatment of CLN3Δex78 neonatal mice by intracerebroventricular injection of the ASO resulted in the desired splicing effect throughout the central nervous system, improved motor deficits associated with the disease in mice, reduced histopathological features of the disease in the brain and extended life in a severe mouse model of the disease. Our results demonstrate that ASO-mediated reading frame correction is a promising therapeutic approach for CLN3 Batten disease.

KEYWORDS: pre-mRNA splicing, Antisense oligonucleotides, Usher syndrome, Batten Disease, lysosomal storage diseases

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Lecture / Discussion Wed, 07 Oct 2020 09:31:00 -0400 2020-11-16T16:00:00-05:00 2020-11-16T17:00:00-05:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion photo
Bioethics Discussion: The Coming Administration (November 24, 2020 7:00pm) https://events.umich.edu/event/58832 58832-14563724@events.umich.edu Event Begins: Tuesday, November 24, 2020 7:00pm
Location: Lurie Biomedical Engineering
Organized By: The Bioethics Discussion Group

A discussion on our (new?) government.

A few readings to consider:
––Three Ways to Politicize Bioethics
––Affording Obamacare
––Confronting Deep Moral Disagreement: The President’s Council on Bioethics, Moral Status, and Human Embryos
––The role of party politics in medical malpractice tort reforms

For more information and/or to receive a copy of the readings visit http://belmont.bme.umich.edu/bioethics-discussion-group/discussions/051-the-coming-administration/.

Please also swing by the blog: https://belmont.bme.umich.edu/incidental-art/

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[OUR FIRST PLANNED REMOTE DISCUSSION]
While people are still allowed on campus, discussions will be held on the front lawn of Lurie Biomedical Engineering building. Participants will be asked to enter the area via a “welcome desk” where there will be hand sanitizer, wipes, etc. Participants will be masked, at least 12 feet from one another, and speaking through megaphones with one another. In accordance with public health mandates and guidance, participation will be limited to 20 individuals who sign up to participate ahead of time.

Sign up here: https://belmont.bme.umich.edu/ask-your-questions-to-ponder/

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Lecture / Discussion Tue, 25 Aug 2020 11:13:08 -0400 2020-11-24T19:00:00-05:00 2020-11-24T20:30:00-05:00 Lurie Biomedical Engineering The Bioethics Discussion Group Lecture / Discussion The Coming Administration
Bioethics Discussion: The Coming Administration (November 24, 2020 7:00pm) https://events.umich.edu/event/58832 58832-20382972@events.umich.edu Event Begins: Tuesday, November 24, 2020 7:00pm
Location: Off Campus Location
Organized By: The Bioethics Discussion Group

A discussion on our (new?) government.

A few readings to consider:
––Three Ways to Politicize Bioethics
––Affording Obamacare
––Confronting Deep Moral Disagreement: The President’s Council on Bioethics, Moral Status, and Human Embryos
––The role of party politics in medical malpractice tort reforms

For more information and/or to receive a copy of the readings visit http://belmont.bme.umich.edu/bioethics-discussion-group/discussions/051-the-coming-administration/.

Please also swing by the blog: https://belmont.bme.umich.edu/incidental-art/

––
[OUR FIRST PLANNED REMOTE DISCUSSION]
While people are still allowed on campus, discussions will be held on the front lawn of Lurie Biomedical Engineering building. Participants will be asked to enter the area via a “welcome desk” where there will be hand sanitizer, wipes, etc. Participants will be masked, at least 12 feet from one another, and speaking through megaphones with one another. In accordance with public health mandates and guidance, participation will be limited to 20 individuals who sign up to participate ahead of time.

Sign up here: https://belmont.bme.umich.edu/ask-your-questions-to-ponder/

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Lecture / Discussion Tue, 25 Aug 2020 11:13:08 -0400 2020-11-24T19:00:00-05:00 2020-11-24T20:30:00-05:00 Off Campus Location The Bioethics Discussion Group Lecture / Discussion The Coming Administration
RNA Seminar featuring: John Mattick, University of New South Wales, Sydney, Australia (December 7, 2020 5:00pm) https://events.umich.edu/event/75816 75816-19608031@events.umich.edu Event Begins: Monday, December 7, 2020 5:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_fCIiMkveTdq3D9-PKFLm6Q

ABSTRACT: The genomic programming of the development of complex organisms appears to have been misunderstood. The human genome contains just ~20,000 protein-coding genes, similar in number and with largely orthologous functions as those in other animals, including simple nematodes with only 1,000 somatic cells. By contrast, the extent of non-protein-coding DNA increases with increasing developmental complexity, reaching 98.8% in humans. Moreover, it is now clear that the majority of the genome is not junk but is differentially and dynamically transcribed to produce not only mRNAs but also tens if not hundreds of thousands of short and long non-protein-coding RNAs that show specific expression patterns and subcellular locations. Many of these noncoding RNAs have evolved rapidly under positive selection for adaptive radiation, and many have been shown to have important roles in development, brain function, cancer and other diseases. They function at many different levels of gene expression and cell biology, including translational control, formation of subcellular (phase-separated) domains, and guidance of the epigenetic processes and chromatin dynamics that underpin development, brain function and physiological adaptation, with plasticity enabled by RNA editing, RNA modification and retrotransposon mobilization. These discoveries mean that the assumption that combinatorial control by transcription factors and other regulatory proteins is sufficient to account for human ontogeny is incorrect, as are the circular assumptions about the neutral evolution of the genome. The challenge now is to determine the structure-function relationships of these RNAs and their mechanisms of action, as well as their place in the decisional hierarchies that control human development, physiology, learning and susceptibility to disorders.

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Lecture / Discussion Tue, 03 Nov 2020 16:51:46 -0500 2020-12-07T17:00:00-05:00 2020-12-07T18:00:00-05:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion photo
Bioethics Discussion: Annihilation (December 8, 2020 7:00pm) https://events.umich.edu/event/58833 58833-14563725@events.umich.edu Event Begins: Tuesday, December 8, 2020 7:00pm
Location: Lurie Biomedical Engineering
Organized By: The Bioethics Discussion Group

A discussion on our obliteration.

[Video-conference link: https://umich.zoom.us/j/94651294615]

A few readings to consider before oblivion:
–– Bioethics and the Metaphysics of Death
––The Ontological Representation of Death: A Scale to Measure the Idea of Annihilation Versus Passage
––The Nonidentity Problem and Bioethics: A Natural Law Perspective
––Controversies in the Determination of Death: A White Paper of the President’s Council on Bioethics

For more information and/or to receive a copy of the readings visit http://belmont.bme.umich.edu/bioethics-discussion-group/discussions/052-annihilation/.

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When the server hosting this blog is turned off, where does the website go: https://belmont.bme.umich.edu/incidental-art/?

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Lecture / Discussion Tue, 08 Dec 2020 15:46:52 -0500 2020-12-08T19:00:00-05:00 2020-12-08T20:30:00-05:00 Lurie Biomedical Engineering The Bioethics Discussion Group Lecture / Discussion Annihilation
RNA Seminar featuring: Narry Kim, Seoul National University (December 14, 2020 4:00pm) https://events.umich.edu/event/75818 75818-19608034@events.umich.edu Event Begins: Monday, December 14, 2020 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

ZOOM REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_c9BFJM9dRGKn1WFF4L_wLg

ABSTRACT: Viruses rely heavily on RNA binding proteins for their success as pathogens. In this presentation, I will first talk about RNA tail modification which impacts viral and cellular gene expression. We found that TENT4 enzymes extend poly(A) tail of mRNAs with ‘mixed tails’ to delay deadenylation and stabilize the RNAs. Hepatitis B virus and human cytomegalovirus hijack this mechanism to efficiently stabilize their own RNAs. In the later part of my presentation, I will discuss our recent work on SARS-CoV-2. To delineate the viral transcriptomic architecture and provide a high-resolution map of SARS-CoV-2, we performed deep sequencing of infected cells. Our data define the canonical transcripts and noncanonical transcripts encoding unknown ORFs. More recently, we have also performed proteomic analyses of the SARS-CoV-2 ribonucleoprotein complex. We identify many proteins that directly interact with viral RNAs and modulate viral growth. Functional investigation of the viral transcripts and host proteins discovered in this study will open new directions to the research efforts to elucidate the life cycle and pathogenicity of SARS-CoV-2.

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Lecture / Discussion Wed, 02 Dec 2020 12:55:41 -0500 2020-12-14T16:00:00-05:00 2020-12-14T17:00:00-05:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Narry Kim, Seoul National University
PhD Defense: Sabrina Lynch (December 15, 2020 10:00am) https://events.umich.edu/event/79855 79855-20509613@events.umich.edu Event Begins: Tuesday, December 15, 2020 10:00am
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via Zoom. The link will be provided below.

Zoom link: https://umich-health.zoom.us/j/94668154127

Thrombosis is a process whereby a blood clot forms in situ within a vessel and impedes flow. Although necessary to maintain hemostasis, the human thrombotic system often becomes unstable leading to scenarios of thrombosis and subsequent diseases such as myocardial infarction, stroke, pulmonary embolism, and deep vein thrombosis. Computational modeling is a powerful tool to understand the complexity of thrombosis initiation and provides both temporal and spatial resolution that cannot be obtained in vivo. The goal of this investigation is to develop a computational model of thrombosis initiation in patient-specific models that includes both a complex description of the hemodynamics and biochemistry of thrombin formation. We argue that the complex hemodynamics occurring in vivo significantly alter the initiation and progression of thrombosis.



While blood viscosity is known to exhibit nonlinear behavior, a Newtonian assumption is often employed in computational analyses. This assumption is valid in healthy arteries where shear rates are high and recirculation is low. However, in pathological geometries, such as aneurysms, and venous geometries, this assumption fails, and nonlinear viscous effects become exceedingly important. Previous computational models of thrombosis have investigated coagulation through chemistry based formulations focusing on protein dynamics but have generally excluded complex 3D hemodynamics.



A computational framework was developed to investigate the interplay between 3D hemodynamics and the biochemical reactions involved in thrombosis initiation in patient-specific models under transient flow. The salient features of the framework are: i) nonlinear rheological models of blood flow; ii) a stabilized numerical framework for scalar mass transport; and iii) a computational interface for nonlinear scalar models of protein dynamics that can be easily customized to include an arbitrary number of species and protein interactions.



We implemented and verified nonlinear rheological models of viscosity into CRIMSON and investigated the effects of non-Newtonian viscosity on both hemodynamic and transport metrics in an arterial and venous patient-specific model. Results demonstrated the importance of considering accurate rheological models.



A stabilized finite element (FE) framework was developed to solve scalar mass transport problems in CRIMSON. Simulation of cardiovascular scalar mass transport problems offers significant numerical challenges such as highly advective flows and flow reversal at outlet boundaries. Furthermore, little attention has been given to the identification of appropriate outflow boundary conditions that preserve the accuracy of the solution. These issues were resolved by developing a stabilized FE framework that incorporates backflow stabilization for Neumann outlet boundaries; a consistent flux boundary condition that minimally disturbs the local physics of the problem; and front-capturing stabilization to regularize solutions in high Pe number flows. The efficacy of these formulations was investigated for both idealized and patient-specific geometries.



Next, a flexible arbitrary reaction-advection-diffusion (ARAD) interface was implemented that enables prototyping nonlinear biochemical models of thrombin generation. After verifying the ARAD interface, the performance was compared against the original hardcoded FORTRAN implementation for speed and accuracy using a 4-scalar nonlinear reaction model of thrombosis. Three different biochemical models of thrombin generation were investigated in idealized geometries. Finally, we implemented the 18 scalar model in both idealized and patient-specific geometries to determine the effects of complex 3D hemodynamics on thrombin generation.



The computational framework for thrombosis initiation presented in this work has three key features: i) non-Newtonian hemodynamics; ii) a stabilized numerical framework for scalar RAD problems; and iii) a method to rapidly prototype custom reaction models using Python with negligible associated computational expense.

Chair: Prof. Alberto C. Figueroa

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Lecture / Discussion Thu, 10 Dec 2020 12:16:10 -0500 2020-12-15T10:00:00-05:00 2020-12-15T11:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Jared Scott (December 22, 2020 2:00pm) https://events.umich.edu/event/79866 79866-20509634@events.umich.edu Event Begins: Tuesday, December 22, 2020 2:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via Zoom. The link will be placed below.

https://umich-health.zoom.us/j/97604985906?pwd=N1Y1UXEvNXMxdjlnVkpjUFZHQkRhdz09

Epilepsy is a debilitating neurological disorder characterized by recurrent spontaneous seizures. While seizures themselves adversely affect physiological function for short time periods relative to normal brain states, their cumulative impact can significantly decrease patient quality of life in myriad ways. For many, anti-epileptic drugs are effective first-line therapies. One third of all patients do not respond to chemical intervention, however, and require invasive resective surgery to remove epileptic tissue. While this is still the most effective last-line treatment, many patients with ‘refractory’ epilepsy still experience seizures afterward, while some are not even surgical candidates. Thus, a significant portion of patients lack further recourse to manage their seizures – which additionally impacts their quality of life.



High-frequency oscillations (HFOs) are a recently discovered electrical biomarker with significant clinical potential in refractory human epilepsy. As a spatial biomarker, HFOs occur more frequently in epileptic tissue, and surgical removal of areas with high HFO rates can result in improved outcomes. There is also limited preliminary evidence that HFOs change prior to seizures, though it is currently unknown if HFOs function as temporal biomarkers of epilepsy and imminent seizure onset. No such temporal biomarker has ever been identified, though if it were to exist, it could be exploited in online seizure prediction algorithms. If these algorithms were clinically implemented in implantable neuromodulatory devices, improvements to quality of life for refractory epilepsy patients might be possible. Thus, the overall aim of this work is to investigate HFOs as potential temporal biomarkers of seizures and epilepsy, and further to determine whether their time-varying properties can be exploited in seizure prediction.



In the first study we explore population-level evidence for the existence of this temporal effect in a large clinical cohort with refractory epilepsy. Using sophisticated automated HFO detection and big-data processing techniques, a continuous measure of HFO rates was developed to explore gradual changes in HFO rates prior to seizures, which were analyzed in aggregate to assess their stereotypical response. These methods resulted in the identification of a subset of patients in whom HFOs from epileptic tissue gradually increased before seizures.



In the second study, we use machine learning techniques to investigate temporal changes in HFO rates within individuals, and to assess their potential usefulness in patient-specific seizure prediction. Here, we identified a subset of patients whose predictive models sufficiently differentiated the preictal (before seizure) state better than random chance.



In the third study, we extend our prediction framework to include the signal properties of HFOs. We explore their ability to improve the identification of preictal periods, and additionally translate their predictive models into a proof-of-concept seizure warning system. For some patients, positive results from this demonstration show that seizure prediction using HFOs could be possible.



These studies overall provide convincing evidence that HFOs can change in measurable ways prior to seizure start. While this effect was not significant in some individuals, for many it enabled seizures to be predicted above random chance. Due to data limitations in overall recording duration and number of seizures captured, these findings require further validation with much larger high-density intracranial EEG datasets. Still, they provide a preliminary framework for the eventual use of HFOs in patient-specific seizure prediction with the potential to improve the lives of those with refractory epilepsy.

Chair: Dr. William Stacey

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Lecture / Discussion Thu, 10 Dec 2020 14:13:29 -0500 2020-12-22T14:00:00-05:00 2020-12-22T15:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Tianrui Luo (December 22, 2020 3:00pm) https://events.umich.edu/event/79858 79858-20509623@events.umich.edu Event Begins: Tuesday, December 22, 2020 3:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via Zoom. The link will be placed below.

https://umich.zoom.us/j/92217348735

Excitation pulse design and image reconstruction are two important topics in MR research for enabling faster imaging. On the pulse design side, selective excitations that confine signals to be within a small region-of-interest (ROI) instead of the full imaging field-of-view (FOV) can be used to reduce sampling density in the k-space, which is a direct outcome of the change in the underlying Nyquist sampling rate. On the reconstruction side, besides improving imaging algorithms’ ability to restore images from less data, another objective is to reduce the reconstruction time, particularly for dynamic imaging applications.



This dissertation focuses on these two perspectives: The first part is devoted to the excitation pulse design. Specifically, we derived and developed a computationally efficient auto-differentiable Bloch-simulator and its explicit Bloch simulation Jacobian operations. This simulator can yield numerical derivatives with respect to pulse RF and gradient waveforms given arbitrary subdifferentiable excitation objective functions. We successfully applied this pulse design approach for jointly designing RF and gradient waveforms for 3D spatially tailored large-tip excitation objectives.



The auto-differentiable pulse design method can yield superior 3D spatially tailored excitation profiles that are useful for inner volume (IV) imaging. We propose and develop a novel steady-state IV imaging strategy which suppresses aliasing by saturating the outer volume (OV) magnetizations via a 3D tailored OV excitation pulse that is followed by a signal crusher gradient. This method substantially suppresses the unwanted OV aliasing for common steady-state imaging sequences.



The second part focuses on non-iterative image reconstruction. In dynamic imaging (e.g., fMRI), where a time series is to be reconstructed, such algorithms may offer savings in overall reconstruction time. We extend the conventional GRAPPA algorithm to work efficiently for general non-Cartesian acquisitions. It attains reconstruction quality that can rival classical iterative imaging methods such as conjugate gradient SENSE and SPIRiT.



In summary, this dissertation has proposed and developed multiple methods for accelerating MR imaging, from pulse design to reconstruction. While devoted to neuroimaging, the proposed methods are general and should also be useful for other applications.

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Lecture / Discussion Thu, 10 Dec 2020 12:29:18 -0500 2020-12-22T15:00:00-05:00 2020-12-22T16:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Charles Park (January 15, 2021 1:00pm) https://events.umich.edu/event/80413 80413-20719667@events.umich.edu Event Begins: Friday, January 15, 2021 1:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held remotely via Zoom. The link will be placed below.

Zoom: https://umich-health.zoom.us/j/97318374664?pwd=YTB4dzNTVXdRZDZQcGR1dVRLZi9JUT09

With the recent progress in technologies, analyzing detailed cellular interactions that constitute the immune system have become possible, and many more biological and engineering tools became within reach for precise investigation and modulation of immune responses. As a result, immunotherapies, such as anti-PD-1 antibody and chimeric antigen receptor T cells, have revolutionized cancer immunotherapy, while genome sequencing and nanotechnology allowed for the rapid development of various vaccines in response to the recent outbreak of Coronavirus Disease 2019. Here, first discussed is modulation of the immune responses using biomaterials, such as silica- or lipid-based nanoparticles and immunomodulating agents for cancer immunotherapy. My approach for immune modulation was to deliver vaccine or pattern recognition receptor-stimulating drugs using nanoparticles to enhance the activation of antigen presenting cells at the innate immune response stage, which leads to stronger adaptive immune responses. In addition, induction of a stronger chemokine gradient to recruit more T cells to tumor from the blood circulation was investigated. In the next study, use of lipid-based nanoparticle to formulate vaccines against infectious diseases, such as human immunodeficiency virus-1 (HIV-1) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is introduced. Nanoparticle-mediated vaccine delivery increases the amount of antigen reaching lymph nodes to interact with immune cells. Also, co-delivery of adjuvants further induces stronger adaptive immune responses. Meanwhile, it is critical to preserve the epitope conformation when protein antigens are used for vaccine formulation, in order to induce functional neutralizing antibodies. The aim of the study was to co-load a subunit protein and an adjuvant into lipid-based nanoparticles while maintaining the structural intactness and induce enhanced antibody responses when vaccinated to animals. Overall, immune modulation strategies are introduced in therapeutic or prophylactic settings, where innate and adaptive immune responses were enhanced using biomaterials-based treatments.

Chair: Dr. James J. Moon

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Lecture / Discussion Wed, 06 Jan 2021 08:23:34 -0500 2021-01-15T13:00:00-05:00 2021-01-15T14:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
KNOWLEDGE EXTRACTION TO ACCELERATE SCIENTIFIC DISCOVERY (January 18, 2021 4:00pm) https://events.umich.edu/event/79534 79534-20373071@events.umich.edu Event Begins: Monday, January 18, 2021 4:00pm
Location: Off Campus Location
Organized By: Michigan Institute for Data Science

To combat COVID-19, clinicians and scientists all need to digest the vast amount of relevant biomedical knowledge in literature to understand the disease mechanism and the related biological functions. The first challenge is quantity. For example, nearly 2.7K new papers are published at PubMed per day. This knowledge bottleneck causes significant delay in the development of vaccines and drugs for COVID-19. The second challenge is quality due to the rise and rapid, extensive publications of preprint manuscripts without pre-publication peer review. Many research results about coronavirus from different research labs and sources are redundant, complementary or event conflicting with each other.

Let’s consider drug repurposing as a case study. Besides the long process of clinical trial and biomedical experiments, another major cause for the long process is the complexity of the problem involved and the difficulty in drug discovery in general. The current clinical trials for drug re-purposing mainly rely on symptoms by considering drugs that can treat diseases with similar symptoms. However, there are too many drug candidates and too much misinformation published from multiple sources. In addition to a ranked list of drugs, clinicians and scientists also aim to gain new insights into the underlying molecular cellular mechanisms on Covid-19, and which pre-existing conditions may affect the mortality and severity of this disease.

To tackle these two challenges, we have developed a novel and comprehensive knowledge discovery framework, COVID-KG, to accelerate scientific discovery and build a bridge between clinicians and biology scientists. COVID-KG starts by reading existing papers to build multimedia knowledge graphs (KGs), in which nodes are entities/concepts and edges represent relations involving these entities, extracted from both text and images. Given the KGs enriched with path ranking and evidence mining, COVID-KG answers natural language questions effectively. Using drug repurposing as a case study, for 11 typical questions that human experts aim to explore, we integrate our techniques to generate a comprehensive report for each candidate drug. Preliminary assessment by expert clinicians and medical school students show our generated reports are informative and sound. I will also talk about our ongoing work to extend this framework to other domains including molecular synthesis and agriculture.

Bio:

Heng Ji is a professor at Computer Science Department, and an affiliated faculty member at Electrical and Computer Engineering Department of University of Illinois at Urbana-Champaign. She is also an Amazon Scholar. She received her B.A. and M. A. in Computational Linguistics from Tsinghua University, and her M.S. and Ph.D. in Computer Science from New York University. Her research interests focus on Natural Language Processing, especially on Multimedia Multilingual Information Extraction, Knowledge Base Population and Knowledge-driven Generation. She was selected as “Young Scientist” and a member of the Global Future Council on the Future of Computing by the World Economic Forum in 2016 and 2017. The awards she received include “AI’s 10 to Watch” Award by IEEE Intelligent Systems in 2013, NSF CAREER award in 2009, Google Research Award in 2009 and 2014, IBM Watson Faculty Award in 2012 and 2014 and Bosch Research Award in 2014-2018, and ACL2020 Best Demo Paper Award. She was invited by the Secretary of the U.S. Air Force and AFRL to join Air Force Data Analytics Expert Panel to inform the Air Force Strategy 2030. She is the lead of many multi-institution projects and tasks, including the U.S. ARL projects on information fusion and knowledge networks construction, DARPA DEFT Tinker Bell team and DARPA KAIROS RESIN team. She has coordinated the NIST TAC Knowledge Base Population task since 2010. She has served as the Program Committee Co-Chair of many conferences including NAACL-HLT2018. She is elected as the North American Chapter of the Association for Computational Linguistics (NAACL) secretary 2020-2021. Her research has been widely supported by the U.S. government agencies (DARPA, ARL, IARPA, NSF, AFRL, DHS) and industry (Amazon, Google, Bosch, IBM, Disney).

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Performance Mon, 23 Nov 2020 09:48:55 -0500 2021-01-18T16:00:00-05:00 2021-01-18T17:00:00-05:00 Off Campus Location Michigan Institute for Data Science Performance Heng Li
BME 500 Seminar - Xiaoning Jiang (January 21, 2021 4:00pm) https://events.umich.edu/event/80996 80996-20830794@events.umich.edu Event Begins: Thursday, January 21, 2021 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via Blue Jeans. The link will be placed below.

Blue Jeans Link: https://bluejeans.com/628109990

Xiaoning Jiang, Ph.D.

North Carolina State University

Seminar Abstract:

Cardiovascular disease (CVD) remains the number one cause of death and the search for more effective diagnosis and treatment techniques has been of a great interest. Ultrasound present a great potential in imaging and therapy for CVD. In this talk, small aperture transducers were designed, fabricated and tested for advanced intravascular ultrasound imaging (IVUS) and effective and safe intravenous sonothrombolysis. In specific, we investigated high frequency (40-60 MHz) micromachined piezoelectric composite transducers and arrays with broad bandwidth (-6 dB fraction bandwidth ~ 80%) for intravascular ultrasound (IVUS) imaging. Dual frequency transducers and arrays (6.5 MHz/30 MHz, 3 MHz/30 MHz) were also successfully demonstrated for contrast enhanced intravascular superharmonic imaging (or acoustic angiography) toward detection of plaque vulnerability. For the case of intravascular thrombolysis, small aperture (diameter &lt;2 mm) sub-MHz forward-looking transducers were successfully developed with peak-negative-pressure of &gt; 1.5 MPa. Significantly enhanced thrombolysis rate was observed by using microbubbles and nanodroplets in in-vitro tests. Other transducer techniques such as optical fiber laser ultrasound transducers were also investigated for intravenous sonothrombolysis. These new findings suggest that small aperture ultrasound transducers are increasingly important in advancing intravascular ultrasound imaging, intravenous therapy, minimal invasive diagnosis and therapy, and image guided drug delivery and surgery.

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Lecture / Discussion Wed, 20 Jan 2021 10:42:47 -0500 2021-01-21T16:00:00-05:00 2021-01-21T17:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
RNA Seminar featuring: Elena Conti, Max Planck Institute of Biochemistry (January 25, 2021 9:00am) https://events.umich.edu/event/75826 75826-19613920@events.umich.edu Event Begins: Monday, January 25, 2021 9:00am
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

KEYWORDS: molecular mechanisms, RNA, ribosome, biochemistry, cryo-EM, X-ray crystallography

ABSTRACT: All RNAs in eukaryotic cells are eventually degraded. The RNA exosome is a conserved macromolecular machine that degrades a vast number and variety of RNAs. Exosome-mediated RNA degradation leads to the complete elimination of nuclear and cytoplasmic transcripts in turnover and quality control pathways, and to the partial trimming of RNA precursors in nuclear processing pathways. How the exosome combines specificity and versatility to either eliminate or process RNAs has been a long-standing question.

ZOOM REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_IjnWw1UcRkW8zcDeuAM2tQ

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Lecture / Discussion Mon, 04 Jan 2021 10:08:44 -0500 2021-01-25T09:00:00-05:00 2021-01-25T10:00:00-05:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Elena Conti, Max Planck Institute of Biochemistry
BME 500 Seminar: Aaron Morris, Ph.D. (January 28, 2021 4:00pm) https://events.umich.edu/event/81261 81261-20879893@events.umich.edu Event Begins: Thursday, January 28, 2021 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via Zoom. The link will be posted below.
https://umich.zoom.us/j/94405051853

Seminar Abstract:

My research program, the Precision Immune Microenvironment (PIM) Lab, will create a minimally invasive toolset for monitoring immune responses within tissues. In my research seminar I will begin by briefly discussing the work I performed with Dr. Themis Kyriakides as a PhD student at Yale - strategies to manipulate the early stages of the foreign body response (FBR) to implanted materials. I will next discuss my work as a postdoctoral fellow at the University of Michigan with Dr. Lonnie Shea. I focus on harnessing the chronic phase of the FBR, as a tool to monitor the immune system. I use biomaterial-based immunological niches to provide insights into the phenotype of innate immune cells that control disease activity. Cells harvested from these niches exhibit differential gene expression sufficient to monitor disease dynamics and to gauge the effectiveness of treatment. I will then discuss work developing sensors for secreted proteins to non-invasively measure protein expression in vivo via luminescence and FRET. I will conclude my talk with a brief discussion of my planned research
program that aims to leverage my materials and immune engineering experience to harness bio-responsive materials as translatable tools for real-time monitoring of tissue immunity.

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Lecture / Discussion Tue, 26 Jan 2021 12:39:22 -0500 2021-01-28T16:00:00-05:00 2021-01-28T17:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
RNA Seminar featuring: Jeff Twiss, MD, PhD, SmartState Chair in Childhood Neurotherapeutics, Professor of Biological Sciences, University of South Carolina (February 1, 2021 4:00pm) https://events.umich.edu/event/75813 75813-19608028@events.umich.edu Event Begins: Monday, February 1, 2021 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_Rss4i-7WTwyf8m8ogCPXEQ

Abstract: Neurons are extremely polarized cells with axonal and dendritic processes extending 100 to 1000 fold longer or more than the cell body diameter. Our lab has been interested in how axons grow to such great distances and how they respond to injury. mRNAs are transported into axons, with their localized translation providing the axon with autonomy to respond to different stimuli by modifying their local proteome. Transport, translation, and stability of axonal mRNAs is driven by interactions with RNA binding proteins and different signaling cascades. I will focus on recent work that gives insight into how specificity of these mechanisms is driven for different cohorts of axonal mRNAs.

Keywords - Neuron, Axon, RNA transport, Translational regulation

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Lecture / Discussion Fri, 15 Jan 2021 14:13:00 -0500 2021-02-01T16:00:00-05:00 2021-02-01T17:00:00-05:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Jeff Twiss, University of South Carolina
BME 500 Seminar: Maria Coronel (February 4, 2021 4:00pm) https://events.umich.edu/event/81382 81382-20889813@events.umich.edu Event Begins: Thursday, February 4, 2021 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

BME Faculty Candidate
Maria Coronel, Ph.D.
Georgia Institute of Technology

Seminar Abstract:
Two major challenges to the translation of cellular-based tissue-engineered therapies are the lack of adequate oxygen support post-implantation and the need for systemic immunosuppression to halt the strong inflammatory and immunological response of the host. As such, strategies that aim at addressing oxygen demand, and local immunological responses can be highly beneficial in the translation of these therapies. In this seminar, I will focus on two biomaterial strategies to create a more favorable transplant niche for pancreatic islet transplantation. The first half will describe an in-situ oxygen-releasing biomaterial fabricated through the incorporation of solid peroxides in a silicone polymer. The implementation of this localized, controlled and sustained oxygen-generator mitigates the activation of detrimental hypoxia-induced pathways in islets and enhances the potency of extrahepatic 3D islet- loaded devices in a diabetic animal model. In the second part, I will focus on engineering synthetic biomaterials for the delivery of immunomodulatory signals for transplant acceptance. Biomaterial carriers fabricated with polyethylene glycol microgels are used to deliver immunomodulatory signals to regulate the local microenvironment and prevent allograft rejection in a clinically relevant pre-clinical transplant model. The use of synthetic materials as an off-the-shelf platform, without the need for manipulating the biological cell product, improves the clinical translatability of this engineered approach. Designing safer, responsive biomaterials to boost the delivery of targeted therapeutics will significantly reinvigorate interventional cell-based tissue-engineered therapies.

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Lecture / Discussion Fri, 29 Jan 2021 17:14:27 -0500 2021-02-04T16:00:00-05:00 2021-02-04T17:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
Bioethics Discussion: Sex (February 9, 2021 7:00pm) https://events.umich.edu/event/58836 58836-14563728@events.umich.edu Event Begins: Tuesday, February 9, 2021 7:00pm
Location: Lurie Biomedical Engineering
Organized By: The Bioethics Discussion Group

A discussion on what we do.

Join us at: https://umich.zoom.us/j/99926126455.

A few readings to consider:
––Sex Differences in Institutional Support for Junior Biomedical Researchers
––Sex as an important biological variable in biomedical research
––Deciding on Gender in Children with Intersex Conditions: Considerations and Controversies
––The Use of Sex Robots: A Bioethical Issue

For more information and/or to receive a copy of the readings visit http://belmont.bme.umich.edu/bioethics-discussion-group/discussions/055-sex/.

––
Not going to make a sex joke. We're above that here. All the same, please come to the blog: https://belmont.bme.umich.edu/incidental-art/

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Lecture / Discussion Fri, 08 Jan 2021 09:42:03 -0500 2021-02-09T19:00:00-05:00 2021-02-09T20:30:00-05:00 Lurie Biomedical Engineering The Bioethics Discussion Group Lecture / Discussion Sex
BME 500 Seminar: Gloria Kim (February 11, 2021 4:00pm) https://events.umich.edu/event/81383 81383-20889814@events.umich.edu Event Begins: Thursday, February 11, 2021 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Seminar Abstract:

The major problems in the current therapy for oncologic diseases include its inability to selectively target specific tumor cells in the surrounding tissues that make it hard for the drugs and treatment to reach the tumor cells. Despite the significant progress in the discovery of surface markers, targeting ligands, and biomaterial carriers, very few nanoparticle drugs are truly tumor-specific after intravenous injection and their targeting is still not fully reliable, which results in a wide distribution of nanoparticles throughout the body and increases the chance of adverse side effects. To overcome such limitations, my graduate research implemented immune cells as living targeting and delivery vehicles that deliver therapeutic biodegradable photoluminescent polymer (BPLP)-based nanoparticles to two tumor models, melanoma and glioblastoma. This system takes advantage of the inherent targeting and penetrating capabilities of immune cells into the tumor target and the fluorescent properties of BPLP nanoparticles for in vivo imaging. Our platform technology allows assembling various types of nanoparticles, drugs, imaging agents, and immune cells as a treatment for different diseases in the future. The second part of the seminar introduces how the immune cells can also be genetically engineered for cancer immunotherapy in vivo. Even with huge success in the development of CD19-targeting chimeric antigen receptor (CAR) T cells for B-cell hematological malignancies, we still face major challenges in expanding adoptive cell transfer for solid tumors. To expand this adoptive cell therapy, finding the right targets for solid tumors that are tumor- and tumor microenvironment-specific is the foremost important step. During my postdoctoral work, we have found an epitope within the collagen alpha-3(VI) (COL6A3) gene, which can be used as a biomarker to target stromal cells associated with multiple solid tumors. COL6A3-specific TCRs were isolated and one of these TCRs was affinity enhanced so that the T cells expressing TCR variants that preserved COL6A3 specificity and endowed both CD4 and CD8 T cells with augmented effector functions were able to specifically eliminate tumors in vivo that expressed similar amount of peptide-human leukocyte antigen (pHLA) as primary tumor specimens with favorable safety profile with no detectable off-target reactivity. These preclinical findings serve as the basis and rationale to initiate clinical trials using COL6A3-specific TCRs to target an array of solid tumors. As a principal investigator, my lab will first focus on merging immunology, synthetic biology, genetic engineering, material science, and biomedical engineering to develop and evaluate the next generation T cell-based therapies that target and kill solid tumors with enhanced specificity, reduced toxicity, and the ability to overcome tumor-associated immunosuppression.

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Lecture / Discussion Fri, 05 Feb 2021 16:15:40 -0500 2021-02-11T16:00:00-05:00 2021-02-11T17:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
RNA Seminar featuring: Karla Neugebauer, Yale University School of Medicine (February 15, 2021 4:00pm) https://events.umich.edu/event/78295 78295-20004839@events.umich.edu Event Begins: Monday, February 15, 2021 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

ZOOM REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_aZggyZ0yQcSPcJrsHloXjQ

ABSTRACT: My lab is interested in the coordination between transcription, RNA processing and nuclear organization that governs gene expression. We have established experimental systems in budding yeast, zebrafish embryos, and mammalian tissue culture cells to explore transcription and splicing regulation in a variety of biological contexts and with a diversity of tools, from imaging to genome-wide approaches. Our observations have provided novel insights into transcription and splicing mechanisms as well as principles of cellular organization that facilitate efficient gene expression. In this talk, I will be discussing rapid co-transcriptional splicing during erythropoiesis and how Cajal bodies assemble to ensure a steady supply of spliceosomal components.

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Lecture / Discussion Tue, 02 Feb 2021 16:32:41 -0500 2021-02-15T16:00:00-05:00 2021-02-15T17:00:00-05:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Prof. Karla Neugebauer, Ph.D.
BME 500 Seminar: Adam Glaser (February 18, 2021 4:00pm) https://events.umich.edu/event/81384 81384-20889815@events.umich.edu Event Begins: Thursday, February 18, 2021 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Seminar Abstract:

New developments in microscopy, tissue clearing, and fluorescent labeling are enabling unprecedented access to the structural and molecular contents of biological tissues. These technologies are now opening new doors in scientific research and shedding light on the critical factors which underpin complex disease processes. In this presentation, I will present my recent work in these areas, with a focus on applications to cancer at both the clinical and preclinical level.

ZOOM LINK: https://umich.zoom.us/j/94405051853

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Lecture / Discussion Sat, 13 Feb 2021 20:04:17 -0500 2021-02-18T16:00:00-05:00 2021-02-18T17:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
Bioethics Discussion: Artificial Life (February 23, 2021 7:00pm) https://events.umich.edu/event/58837 58837-14563729@events.umich.edu Event Begins: Tuesday, February 23, 2021 7:00pm
Location: Off Campus Location
Organized By: The Bioethics Discussion Group

A discussion on new forms.

Join us at: https://umich.zoom.us/j/99926126455.

A few readings to consider:
––Is the creation of artificial life morally significant?
––Why Do We Need Artificial Life?
––Artificial Life
––The Bioethicist Who Cried “Synthetic Biology”: An Analysis of the Function of Bioterrorism Predictions in Bioethics

For more information and/or to receive a copy of the readings visit http://belmont.bme.umich.edu/bioethics-discussion-group/discussions/056-artificial-life/.

––
Life finds a way over to the blog: https://belmont.bme.umich.edu/incidental-art/

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Lecture / Discussion Fri, 08 Jan 2021 09:41:49 -0500 2021-02-23T19:00:00-05:00 2021-02-23T20:30:00-05:00 Off Campus Location The Bioethics Discussion Group Lecture / Discussion Artificial Life
BME 500 Seminar: Jorge Marchand (February 25, 2021 4:00pm) https://events.umich.edu/event/81385 81385-20889816@events.umich.edu Event Begins: Thursday, February 25, 2021 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Seminar Abstract:

In living organisms, translation of genetic information by the ribosome transforms
the information embedded in DNA into actuating components, namely proteins. Though life itself is incredibly diverse at the macroscopic level, at the molecular level, all of life uses the same set of machinery for translation - 20 standard amino acid building blocks (with minor exceptions), transfer RNAs (tRNA), and ribosomes. The convergence and association of these interdependent biomolecules is neatly captured in a table known as the ‘standard genetic code’. Even after billions of years of genetic drift, the ‘standard genetic code’ has been largely refractory to change. In this talk, I will be discussing strategies and methods for building organisms that can make and use non-standard amino acids to make proteins with enhanced or expanded function.

ZOOM LINK: https://umich.zoom.us/j/94405051853

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Lecture / Discussion Sun, 21 Feb 2021 22:07:28 -0500 2021-02-25T16:00:00-05:00 2021-02-25T17:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
RNA Seminar featuring: Melissa Moore, Moderna Therapeutics (March 3, 2021 4:00pm) https://events.umich.edu/event/81265 81265-20879904@events.umich.edu Event Begins: Wednesday, March 3, 2021 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

**Please register here for March 3rd seminar: https://umich.zoom.us/webinar/register/WN_l0kt_NjpRh-f33LJj7KGpA

Dr. Moore will address scientists and non-scientists, and will take live questions.

In her role as Chief Scientific Officer, Platform Research, Dr. Melissa Moore is responsible for leading mRNA biology, delivery and computation science research at Moderna. She joined Moderna in 2016 from the University of Massachusetts Medical School, where she served as Professor of Biochemistry & Molecular Pharmacology, Eleanor Eustis Farrington Chair in Cancer Research and a long-time Investigator at the Howard Hughes Medical Institute (HHMI). Dr. Moore was also a founding Co-Director of the RNA Therapeutics Institute (RTI) at UMassMed, and was instrumental in creating the Massachusetts Therapeutic and Entrepreneurship Realization initiative (MassTERi), a faculty-led program intended to facilitate the translation of UMMS discoveries into drugs, products, technologies and companies. Dr. Moore is an elected member of the National Academy of Sciences (2017) and a Fellow of the American Academy of Arts and Sciences (2019).

Dr. Moore holds a B.S. in Chemistry and Biology from the College of William and Mary, and a Ph.D. in Biological Chemistry from MIT, where she specialized in enzymology under Prof. Christopher T. Walsh. She began working on RNA metabolism during her postdoctoral training with Phillip A. Sharp at MIT. During her 23 years as a faculty member, first at Brandeis and then at UMassMed, her research encompassed a broad array of topics related to the roles of RNA and RNA-protein (RNP) complexes in gene expression, and touched on many human diseases including cancer, neurodegeneration, and preeclampsia.

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Lecture / Discussion Wed, 10 Feb 2021 19:47:49 -0500 2021-03-03T16:00:00-05:00 2021-03-03T17:00:00-05:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Melissa Moore, Ph.D., Moderna Therapeutics
BME 500 Seminar: Danielle Bassett (March 4, 2021 4:00pm) https://events.umich.edu/event/81388 81388-20889818@events.umich.edu Event Begins: Thursday, March 4, 2021 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

TBD

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Lecture / Discussion Wed, 27 Jan 2021 21:05:02 -0500 2021-03-04T16:00:00-05:00 2021-03-04T17:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
BME 500 Seminar: Sasha Cai Lesher-Perez (March 4, 2021 4:00pm) https://events.umich.edu/event/81387 81387-20889817@events.umich.edu Event Begins: Thursday, March 4, 2021 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Efforts to close the gap between in vitro to in vivo model systems have produced technologies that more effectively evaluate spatial, structural, and mechanical control mechanisms. However, existing in vitro models lack temporal regulation that captures the controlled, rhythmic processes that often occur in biological phenomena. A major contributor to this tech-bio mismatch is the difficulty to easily and sustainably scale our ability to apply timed oscillations, representative of biorhythms, in vitro. Developing technologies that are simpler and more adoptable for users, while ensuring higher throughput, have the potential to shift the way in which we establish cell cultures with a dynamic biorhythmic baseline.

In this talk, I will cover how my previous work in different technology platforms will be leveraged to establish next generation cell and tissue culture platforms that enable biomolecule timed oscillations in more complex microenvironments. First, I will discuss the development of microfluidic self-regulating circuits as a tool to produce modular chemical profiles on-chip at different timescales. Second, I will describe microparticle building blocks for the generation of customizable porous scaffolds that are porous, and consequently perfusable, enabling our ability to apply biomolecule timed oscillations through liquid flow to 3D scaffolds. Finally, I will describe my proposed research on establishing biorhythms in vitro and how these in vitro model systems will enable my research group to begin studying how stress within our lives lead to specific disease priming mechanisms.

ZOOM LINK: https://umich.zoom.us/j/94405051853

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Lecture / Discussion Fri, 26 Feb 2021 16:50:20 -0500 2021-03-04T16:00:00-05:00 2021-03-04T17:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
Viral hijacking of host molecular motors to promote nuclear entry (March 5, 2021 12:00pm) https://events.umich.edu/event/82373 82373-21084381@events.umich.edu Event Begins: Friday, March 5, 2021 12:00pm
Location: Off Campus Location
Organized By: Department of Molecular, Cellular, and Developmental Biology

During entry, most DNA viruses must navigate the crowded cellular environment to reach the nucleus where transcription and replication of the viral genome occur. How polyomavirus (PyV), a small, DNA tumor virus, accomplishes this essential step in infection is unclear. In mammalian cells, intracellular transport is facilitated largely by two host motors, kinesin and cytoplasmic dynein, which move cargo along microtubules towards the periphery and center of the cell, respectively. We reported that dynein motor activity is required for PyV disassembly and nuclear arrival, but the exact mechanisms by which it promotes this process were unknown. Processive dynein activity requires a three-protein complex composed of the dynein motor, dynactin activator and an adaptor that confers cargo specificity. Unexpectedly, our most recent data revealed that the BICD2 adaptor is sufficient to disassemble the virus independent of the other components within the complex revealing cargo remodeling as a novel function of dynein adaptors. As BICD2 associates with both dynein and kinesin and is involved in cargo transport to the nuclear membrane, we are now investigating the role of these factors in the subsequent nuclear arrival and import of PyV.

Host: Matt Chapman

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Workshop / Seminar Sun, 21 Feb 2021 16:28:01 -0500 2021-03-05T12:00:00-05:00 2021-03-05T13:30:00-05:00 Off Campus Location Department of Molecular, Cellular, and Developmental Biology Workshop / Seminar Chelsey Spriggs
Bioethics Discussion: Infection (March 9, 2021 7:00pm) https://events.umich.edu/event/58838 58838-14563730@events.umich.edu Event Begins: Tuesday, March 9, 2021 7:00pm
Location: Off Campus Location
Organized By: The Bioethics Discussion Group

A discussion spreading to others.

Join us at: https://umich.zoom.us/j/99926126455.

A few readings to consider:
––Evidence and Effectiveness in Decision-Making for Quarantine
––The 1918 Influenza Pandemic: Insights for the 21st Century
––From SARS to Ebola: Legal and Ethical Considerations for Modern Quarantine
––Responding to the COVID-19 pandemic: Ethical considerations for conducting controlled human infection studies

For more information and/or to receive a copy of the readings visit http://belmont.bme.umich.edu/bioethics-discussion-group/discussions/057-infection/.

––
Feel free to stop by the website, not even the blog is viral: https://belmont.bme.umich.edu/incidental-art/

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Lecture / Discussion Fri, 08 Jan 2021 09:40:23 -0500 2021-03-09T19:00:00-05:00 2021-03-09T20:30:00-05:00 Off Campus Location The Bioethics Discussion Group Lecture / Discussion Infection
BME 500 Seminar: George Christ (March 11, 2021 4:00pm) https://events.umich.edu/event/81389 81389-20889819@events.umich.edu Event Begins: Thursday, March 11, 2021 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Despite the well-documented capability of skeletal muscle to repair, regenerate, and remodel following injury, there remain a multitude of diseases, disorders, and traumatic injuries that result in irrecoverable loss of muscle structure and function. For example, volumetric muscle loss (VML) injuries are characterized by a degree of composite muscle tissue loss so severe, that it exceeds the native ability of the muscle to repair, thereby resulting in permanent cosmetic and functional deficits to the limbs, neck, or face. These injuries significantly impact both the civilian and military populations. Current treatment for VML injury involves surgical muscle transfer, although these procedures are often associated with both poor engraftment and donor site morbidity, as well as incomplete cosmesis and functional recovery. Not surprisingly, this unmet medical need has stimulated research efforts to develop new technologies for treatment of VML injuries. Recent attention has focused on development of tissue engineering (TE)/regenerative medicine (RM) technologies to provide more effective treatment options for large scale muscle injuries. A variety of preclinical approaches have been tried that include implantation of synthetic and/or natural extracellular matrices/scaffolds/constructs at the site of VML injury, both with and without a cellular component. Extant data indicate that the inclusion of a cellular component generally leads to a greater degree of functional improvement. Consistent with these preclinical results, recent clinical studies for treatment of VML injury, solely with implanted decellularized extracellular matrix scaffolds, have provided evidence for modest functional recovery but with little de novo muscle tissue regeneration at the injury site. More recently, bio-printed tissue engineered constructs and their potential applications to treatment of VML injury have been reported in the literature. While these initial clinical and preclinical observations are encouraging for the TE/RM paradigm, full structural and functional recovery has yet to be achieved, and thus, there remains significant room for therapeutic advancement. To this end, I will describe our highly collaborative efforts to boost development and evaluation of a range of implantable regenerative therapeutics (biomaterials and tissue engineered constructs) in biologically relevant animal models. The overall goal is to increase the efficiency of clinical translation of TE/RM technologies capable of more complete functional recovery following repair of VML injury.

ZOOM LINK: https://umich.zoom.us/j/94405051853

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Lecture / Discussion Mon, 08 Mar 2021 11:13:19 -0500 2021-03-11T16:00:00-05:00 2021-03-11T17:00:00-05:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
RNA Seminar featuring: James Nuñez, HHMI Hanna Gray Fellow, University of California, San Francisco (March 15, 2021 4:00pm) https://events.umich.edu/event/81286 81286-20881887@events.umich.edu Event Begins: Monday, March 15, 2021 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_f8wC8rrJQzuhYzTEXoW69Q


ABSTRACT
General approaches for heritably altering gene expression would enable many discovery and therapeutic efforts. I will present CRISPRoff— a programmable epigenetic memory writer consisting of a single dead Cas9 fusion protein that establishes DNA methylation and repressive histone modifications to turn off transcription. Transient CRISPRoff expression initiates highly specific DNA methylation and gene repression that is maintained through cell division and differentiation of stem cells to neurons. Pairing CRISPRoff with genome-wide screens and analysis of chromatin marks enabled us to explore the rules for heritable silencing. We identify sgRNAs capable of silencing the large majority of genes including those lacking canonical CpG islands (CGIs) and reveal a wide targeting window extending beyond annotated CGIs. Our finding that targeted DNA methylation outside of CGIs leads to memorized gene silencing expands the canonical model of methylation-based silencing and broadly enables diverse applications including genome-wide screens, multiplexed cell engineering, enhancer silencing, and mechanistic exploration of epigenetic inheritance.

KEYWORDS: CRISPR, transcription, epigenetics
Flyer in PDF: https://rna.umich.edu/wp-content/uploads/2021/02/Seminar-Flyer-03152021-Nunez.pdf

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Lecture / Discussion Thu, 18 Feb 2021 09:21:31 -0500 2021-03-15T16:00:00-04:00 2021-03-15T17:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion James Nunez, Ph.D. UCSF
BME 500 Seminar: Daniel Rueckert (March 18, 2021 4:00pm) https://events.umich.edu/event/81390 81390-20889820@events.umich.edu Event Begins: Thursday, March 18, 2021 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Zoom Link: https://cwru.zoom.us/webinar/register/WN_tmHJ7ArQRyO01NN6SfYYtg

Hosted by Dr. Frederick Epstein

Seminar Abstract:
The talk will focus on the use of deep learning techniques for the discovery and quantification of clinically useful information from medical images. The talk will describe how deep learning can be used for the reconstruction of medical images from undersampled data, image super-resolution, image segmentation and image classification. It will also show the clinical utility of applications of deep learning for the interpretation of medical images in applications such as brain tumour segmentation, cardiac image analysis and applications in neonatal and fetal imaging. Finally, it will be discussed how deep learning may change the future of medical imaging. https://openbme.org/

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Lecture / Discussion Mon, 15 Mar 2021 14:07:10 -0400 2021-03-18T16:00:00-04:00 2021-03-18T17:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
"Coming together in challenging times: Multicellular assembly in engineered microenvironments" (March 23, 2021 4:00pm) https://events.umich.edu/event/83016 83016-21243198@events.umich.edu Event Begins: Tuesday, March 23, 2021 4:00pm
Location: Off Campus Location
Organized By: Center for Cell Plasticity and Organ Design

The Center for Cell Plasticity and Organ Design, alongside the Department of Biomedical Engineering, is proud to present a seminar with guest speaker Brendon M. Baker, PhD.

Dr. Baker is an Assistant Professor of Biomedical Engineering at the University of Michigan.

The talk is entitled, "Coming together in challenging times: Multicellular assembly in engineered microenvironments"

Faculty Host: Ariella Shikanov, PhD, Associate Professor of Biomedical Engineering

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Lecture / Discussion Wed, 17 Mar 2021 15:35:19 -0400 2021-03-23T16:00:00-04:00 2021-03-23T17:00:00-04:00 Off Campus Location Center for Cell Plasticity and Organ Design Lecture / Discussion Flyer for the Event
Bioethics Discussion: Accidents (March 23, 2021 7:00pm) https://events.umich.edu/event/58839 58839-14563731@events.umich.edu Event Begins: Tuesday, March 23, 2021 7:00pm
Location: Off Campus Location
Organized By: The Bioethics Discussion Group

A discussion we were not meant to have.

Join us at: https://umich.zoom.us/j/99926126455.

A few readings to consider:
––Defining Failure: The Language, Meaning and Ethics of Medical Error
––Taking the blame: appropriate responses to medical error
––Medical Error and Moral Luck
––When AIs Outperform Doctors: Confronting the Challenges of a Tort-Induced Over-Reliance on Machine Learning

For more information and/or to receive a copy of the readings visit http://belmont.bme.umich.edu/bioethics-discussion-group/discussions/058-accidents/.

––
By accident, by choice, or not at all, the three ways of arriving somewhere, such as the blog: https://belmont.bme.umich.edu/incidental-art/

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Lecture / Discussion Fri, 08 Jan 2021 09:39:36 -0500 2021-03-23T19:00:00-04:00 2021-03-23T20:30:00-04:00 Off Campus Location The Bioethics Discussion Group Lecture / Discussion Accidents
5th Annual RNA Symposium, "Processing RNA" (March 25, 2021 11:00am) https://events.umich.edu/event/80161 80161-20572609@events.umich.edu Event Begins: Thursday, March 25, 2021 11:00am
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

FOR MORE DETAILS & ABSTRACTS VISIT: https://rna.umich.edu/2021-symposium/

Thursday, March 25, 2021
11:00 / Welcome
11:05 / KEYNOTE 1: Tracy Johnson, UCLA, “RNA Splicing, Chromatin Modification, and the Coordinated Control of Gene expression”
12:00 / Short break
12:10 / KEYNOTE 2: Kevin Weeks, UNC, “Structure-Based Discovery of New Functions in Large RNAs”
1:05 / Data Blitz: Cathy Smith, Daniel Peltier, Yan Zhang
1:35 / KEYNOTE 3: Feng Zhang, MIT, “Exploration of Biological Diversity to Discover Novel Molecular Technologies”
2:30 / Close Day 1

Friday, March 26, 2021
11:00 / Welcome
11:05 / KEYNOTE 4: Brenda Bass, University of Utah, “Distinguishing self and non-self dsRNA in vertebrates and invertebrates”
12:00 / Short break
12:10 / KEYNOTE 5: Christopher Lima, Sloan-Kettering Institute, “Mechanisms that target RNA for destruction”
1:05 / Data Blitz: Meredith Purchal, Adrien Chauvier, Shannon Wright
1:35 / Panel discussion with keynote speakers
2:30 / Close Day 2

Liveblogging by MiSciWriters! https://misciwriters.com/

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Lecture / Discussion Tue, 23 Mar 2021 15:03:26 -0400 2021-03-25T11:00:00-04:00 2021-03-25T14:30:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion 5th Annual RNA Symposium
BME 500 Seminar: Warren L. Grayson (March 25, 2021 4:00pm) https://events.umich.edu/event/81391 81391-20889821@events.umich.edu Event Begins: Thursday, March 25, 2021 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Tissue engineering provides a viable means of regenerating bone and skeletal muscle tissues following injuries that lead to large volumetric defects. Our lab has developed advanced biomaterial and stem cell-based approaches to promote functional recovery following volumetric muscle loss and critical-sized craniofacial bone injuries. This presentation will focus on three areas of ongoing research: (1) I will present our lab’s efforts to regenerate vascularized and innervated skeletal muscle in mice including our recent studies using human pluripotent stem cells. (2) Recently, our group completed a study focused on designing biomaterials to guide bone regeneration in situ in minipigs using intraoperative protocols for combining autologous stem cells with 3D-printed scaffolds. (3) Understanding the interaction between vascular cells and osteoprogenitors is critical for developing effective treatment methods. I will describe recent studies in which we developed a quantitative imaging platform for characterizing the spatial relationships between cell populations in the native murine calvarium. https://openbme.org/

ZOOM LINK TO REGISTER: https://cwru.zoom.us/webinar/register/WN_Kgyl3yf4TcKvlk9xNKluhA

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Lecture / Discussion Sun, 21 Mar 2021 17:46:23 -0400 2021-03-25T16:00:00-04:00 2021-03-25T17:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
5th Annual RNA Symposium, "Processing RNA" (March 26, 2021 11:00am) https://events.umich.edu/event/80161 80161-20572610@events.umich.edu Event Begins: Friday, March 26, 2021 11:00am
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

FOR MORE DETAILS & ABSTRACTS VISIT: https://rna.umich.edu/2021-symposium/

Thursday, March 25, 2021
11:00 / Welcome
11:05 / KEYNOTE 1: Tracy Johnson, UCLA, “RNA Splicing, Chromatin Modification, and the Coordinated Control of Gene expression”
12:00 / Short break
12:10 / KEYNOTE 2: Kevin Weeks, UNC, “Structure-Based Discovery of New Functions in Large RNAs”
1:05 / Data Blitz: Cathy Smith, Daniel Peltier, Yan Zhang
1:35 / KEYNOTE 3: Feng Zhang, MIT, “Exploration of Biological Diversity to Discover Novel Molecular Technologies”
2:30 / Close Day 1

Friday, March 26, 2021
11:00 / Welcome
11:05 / KEYNOTE 4: Brenda Bass, University of Utah, “Distinguishing self and non-self dsRNA in vertebrates and invertebrates”
12:00 / Short break
12:10 / KEYNOTE 5: Christopher Lima, Sloan-Kettering Institute, “Mechanisms that target RNA for destruction”
1:05 / Data Blitz: Meredith Purchal, Adrien Chauvier, Shannon Wright
1:35 / Panel discussion with keynote speakers
2:30 / Close Day 2

Liveblogging by MiSciWriters! https://misciwriters.com/

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Lecture / Discussion Tue, 23 Mar 2021 15:03:26 -0400 2021-03-26T11:00:00-04:00 2021-03-26T14:30:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion 5th Annual RNA Symposium
Biointerfaces Institute Distinguished Lectureship Series (March 30, 2021 3:30pm) https://events.umich.edu/event/82755 82755-21171618@events.umich.edu Event Begins: Tuesday, March 30, 2021 3:30pm
Location: Off Campus Location
Organized By: Biointerfaces Institute

Lecture Title:
Aging, Cellular Senescence, and Senolytic Drugs: The Path to Translation

Speaker:
Dr. James Kirland
Director of the Robert and Arlene Kogod Center on Aging at Mayo Clinic and Noaber Foundation Professor of Aging Research

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Lecture / Discussion Thu, 04 Mar 2021 16:09:14 -0500 2021-03-30T15:30:00-04:00 2021-03-30T16:30:00-04:00 Off Campus Location Biointerfaces Institute Lecture / Discussion Seminar Flyer
BME 500 Seminar: Tim Downing (April 1, 2021 4:00pm) https://events.umich.edu/event/81392 81392-20889822@events.umich.edu Event Begins: Thursday, April 1, 2021 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

https://openbme.org/

ZOOM LINK TO REGISTER: https://cwru.zoom.us/webinar/register/WN_iY_PMZevQwWRYkMyK7ifzA

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Lecture / Discussion Fri, 26 Mar 2021 14:01:59 -0400 2021-04-01T16:00:00-04:00 2021-04-01T17:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
RNA Seminar featuring: Natoya Peart, PhD, University of Pennsylvania (April 5, 2021 4:00pm) https://events.umich.edu/event/81288 81288-20881888@events.umich.edu Event Begins: Monday, April 5, 2021 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

Registration required: https://umich.zoom.us/webinar/register/WN_0lUfePb0Qdac-cQZDpeiEQ


KEYWORDS: Alternative splicing, RNAMap, Esrp1

ABSTRACT: Coordinated regulation of alternative splicing is essential to the establishment of cell identity. The Epithelial Splicing Regulatory Proteins (Esrps), ESRP1 and ESRP2, are highly conserved paralogous proteins required for organogenesis of multiple organ systems and compromised function of Esrps contributes to human diseases and pathologies. Esrps are robustly expressed in the epithelial cells of the epidermis, large and small intestines, salivary glands, stomach, and a variety of other tissues, where they are vital in promoting an epithelial splicing network. Although ESRP1 and ESRP2 share partial functional redundancy, ESRP1 appears to play a larger role in regulating gene expression.
Using a combination of enhanced immunoprecipitation coupled with high throughput sequencing (eCLIP) in the epithelial cells of mouse epidermis and RNA sequencing analysis of alterations in splicing and total gene expression that result from epidermal ablation of Esrp1 and Esrp2 we generate a map of Esrp1 binding to RNA. We show that ESRP1 regulates splicing primarily through direct binding in a position-dependent manner to either promote exon inclusion or skipping. In particular, we show that Esrp1 binding upstream of or withing alternatively spliced exons suppresses exon inclusion, whilst binding downstream of the non-constitutive exon promotes exon inclusion. In addition, we identified widespread binding of ESRP1 in 3’ and 5’ untranslated regions (UTRs) of genes enriched for epithelial cell function suggesting that it directly regulates post-transcriptional gene expression steps in addition to splicing.


If you are having difficulties registering, please contact Martina Jerant at mjerant@umich.edu

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Lecture / Discussion Mon, 08 Mar 2021 12:23:08 -0500 2021-04-05T16:00:00-04:00 2021-04-05T17:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Natoya Peart, PhD, University of Pennsylvania
Bioethics Discussion: Virtual Reality (April 6, 2021 7:00pm) https://events.umich.edu/event/58840 58840-14563732@events.umich.edu Event Begins: Tuesday, April 6, 2021 7:00pm
Location: Lurie Biomedical Engineering
Organized By: The Bioethics Discussion Group

A discussion like any other?

Join us at: https://umich.zoom.us/j/99926126455.

A few reading to consider:
––Internet-Delivered Health Interventions That Work: Systematic Review of Meta-Analyses and Evaluation of Website Availability
––Ethics of Virtual Reality in Medical Education and Licensure
––Wearables and the medical revolution
––Creating Bioethics Distance Learning Through Virtual Reality

For more information and/or to receive a copy of the readings visit http://belmont.bme.umich.edu/bioethics-discussion-group/discussions/059-virtual-reality/.

––
A decently maintained virtual reality may be found on the blog: https://belmont.bme.umich.edu/incidental-art/

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Lecture / Discussion Fri, 08 Jan 2021 09:39:24 -0500 2021-04-06T19:00:00-04:00 2021-04-06T20:30:00-04:00 Lurie Biomedical Engineering The Bioethics Discussion Group Lecture / Discussion Virtual Reality
Biointerfaces Institute Distinguished Lectureship Series (April 7, 2021 1:00pm) https://events.umich.edu/event/83431 83431-21377664@events.umich.edu Event Begins: Wednesday, April 7, 2021 1:00pm
Location: Off Campus Location
Organized By: Biointerfaces Institute

Lecture Title:
Droplet Microfluidics for Ultra-High Throughput Screening and Super Sensitive Detection

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Workshop / Seminar Tue, 30 Mar 2021 14:19:46 -0400 2021-04-07T13:00:00-04:00 2021-04-07T14:00:00-04:00 Off Campus Location Biointerfaces Institute Workshop / Seminar Seminar Flyer
BME 500 Seminar: James Collins (April 8, 2021 4:00pm) https://events.umich.edu/event/81393 81393-20889823@events.umich.edu Event Begins: Thursday, April 8, 2021 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

James Collins, Ph.D.
Massachusetts Institute of Technology

https://openbme.org/

ZOOM LINK TO REGISTER: https://cwru.zoom.us/webinar/register/WN_MSUiecgNTLyXR5bM8HSnR

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Lecture / Discussion Fri, 02 Apr 2021 15:01:39 -0400 2021-04-08T16:00:00-04:00 2021-04-08T17:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
BME 500 Seminar: Kelly J. Cross (April 15, 2021 4:00pm) https://events.umich.edu/event/81394 81394-20889824@events.umich.edu Event Begins: Thursday, April 15, 2021 4:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Join us for a virtual seminar series on topics related to race and science, technology, engineering and math (STEM) education. https://happenings.wustl.edu/event/an_honest_conversation_about_inequity_in_engineering#.YG9vT-hKhPY

Details:
DATE: Thursday, April 15, 2021
TIME: 4:00-5:00 PM
ZOOM LINK TO REGISTER: https://wustl.zoom.us/webinar/register/WN_NvH4qVTSRx2uSXbdW-eXNA

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Lecture / Discussion Wed, 14 Apr 2021 14:13:34 -0400 2021-04-15T16:00:00-04:00 2021-04-15T17:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
BME Master's Defense: Fatimah Alkaabi (April 16, 2021 12:00pm) https://events.umich.edu/event/83558 83558-21424731@events.umich.edu Event Begins: Friday, April 16, 2021 12:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

The central auditory system consists of the brain nuclei that transmit peripheral auditory nerve input to the auditory cortex for hearing perception. Damage to the auditory end organ, the cochlea, can result in hearing loss that drives the central auditory system to disarray causing disorders such as hyperacusis and tinnitus. These disorders can negatively affect patients’ quality of life. Tinnitus sufferers generally describe their tinnitus as a narrowband of sound that occurs in quiet, while hyperacusis sufferers express an exaggerated perception of sound level or intensity. These two disorders are often grouped together because tinnitus sufferers tend to report symptoms of hyperacusis and vice versa. However, hyperacusis and tinnitus do not always co-occur, suggesting that they have different neural origins. To study these conditions, researchers have induced cochlear damage in animal models, followed by behavioral and electrophysiological assessments. However, no study has adequately distinguished hyperacusis from tinnitus in individual animals. In this thesis, I detail the development of a novel hyperacusis and tinnitus assessment paradigm for individual animals using the pinna reflex combined with auditory brainstem responses (ABR). In the first chapter, I detail several enhancements to a computer system that ensures accurate sound presentation concurrently with capture of pinna reflex video data, as well as streamlines the subsequent data analysis. In the second chapter, the ABR, an evoked potential reflecting the summed electrical activity of cells in the auditory brainstem pathway, was assessed. Several studies suggest that ABR-wave characteristics might provide evidence of hyperacusis. ABRs were evoked using conventional and novel sound stimuli. They were then examined to look for possible indications of hyperacusis in noise overexposed guinea pigs. The present findings are discussed with several suggestions for future hyperacusis assessments.



Date: Friday, April 16, 2021

Time: 12:00 PM

Zoom: https://umich.zoom.us/j/91698183229

Chair: Dr. Susan Shore

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Lecture / Discussion Mon, 05 Apr 2021 23:04:39 -0400 2021-04-16T12:00:00-04:00 2021-04-16T13:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
RNA Seminar featuring: Jailson (Jay) Brito Querido, Ph.D. MRC Laboratory of Molecular Biology, Cambridge, UK (April 19, 2021 4:00pm) https://events.umich.edu/event/81408 81408-20893767@events.umich.edu Event Begins: Monday, April 19, 2021 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

REGISTRATION REQUIRED: https://umich.zoom.us/webinar/register/WN_78YYOhIhTbOBy2_JSdM7Wg

ABSTRACT: A key step in translational initiation is the recruitment of the 43S pre-initiation complex (43S PIC) by the cap-binding complex (eIF4F) at the 5´ end of mRNA. Eukaryotic initiation factors eIF1, eIF1A, eIF3, eIF5, and the ternary complex (TC) of eIF2–GTP–tRNAiMet bind to the 40S ribosomal subunit to form the 43S PIC. Once assembled, the 43S PIC is recruited to the cap-binding complex eIF4F at the 5´end of mRNA to form a 48S initiation complex (48S). The 48S then scans along the mRNA to locate a start codon. To understand the mechanisms involved, we determined the structure of a reconstituted human 48S using cryo-electron microscopy. The structure reveals insights into early events of translation initiation complex assembly. It reveals how eIF4F interacts with subunits of the eIF3 structural core near the mRNA exit channel in the 43S. The location of eIF4F is consistent with a slotting model of mRNA recruitment and suggests a “blind-region” that would preclude recognition of start sites upstream of the location of the P site at the point of recruitment.

KEYWORDS: mRNA, ribosome, eIF4F, eIF4A, translation

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Lecture / Discussion Tue, 13 Apr 2021 12:58:40 -0400 2021-04-19T16:00:00-04:00 2021-04-19T17:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Jailson (Jay) Brito Querido, Ph.D.
Bioethics Discussion: Abdication (April 20, 2021 7:00pm) https://events.umich.edu/event/58841 58841-14563735@events.umich.edu Event Begins: Tuesday, April 20, 2021 7:00pm
Location: Lurie Biomedical Engineering
Organized By: The Bioethics Discussion Group

A discussion on our renunciation.

Join us at: https://umich.zoom.us/j/99926126455

A few readings to consider:
––The Idea of Legitimate Authority in the Practice of Medicine
––Decentralization of health care systems and health outcomes: Evidence from a natural experiment
––Vox Populi or Abdication of Responsibility?: The Influence of the Irish Citizens’ Assembly on the Public Discourse Regarding Abortion, 2016-2019
––Lifeboat Ethics: The Case Against Helping the Poor
For more information and/or to receive a copy of the readings visit http://belmont.bme.umich.edu/bioethics-discussion-group/discussions/060-abdication/.

––
Before you give up, consider the blog: https://belmont.bme.umich.edu/incidental-art/

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Lecture / Discussion Fri, 08 Jan 2021 09:38:57 -0500 2021-04-20T19:00:00-04:00 2021-04-20T20:30:00-04:00 Lurie Biomedical Engineering The Bioethics Discussion Group Lecture / Discussion Abdication
Master's Defense: Annie Taylor (April 21, 2021 10:30am) https://events.umich.edu/event/83750 83750-21485477@events.umich.edu Event Begins: Wednesday, April 21, 2021 10:30am
Location: Off Campus Location
Organized By: Biomedical Engineering

Dopamine regulates motor performance and learning. Current models suggest that dopamine signals reward-prediction errors and/or movement vigor. These functions have been assessed predominantly using simple behavioral tasks. The role of dopamine in dexterous skill, however, is unknown. This question is important to understanding motor disorders such as Parkinson's Disease. Here we describe an experimental model to interrogate the role of dopamine release during learning and performance of dexterous skill. Fluorescent sensors dLight1.1 and GCaMP are used to monitor dopamine and calcium activity in the striatum and substantia nigra pars compacta (SNc) in rats performing skilled reaching tasks. Preliminary experiments have successfully recorded reward-associated signals in both striatum and SNc. Adaptations to the recording setup to facilitate long-term recording in larger rodents are described. These results demonstrate the viability of fiber photometry for measuring dopamine-related activity during skilled reaching tasks.



Date: Wednesday April 21, 2021

Time: 10:30 AM

Zoom: https://umich.zoom.us/j/96449273959

Chair: Dr. Dan Leventhal

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Lecture / Discussion Tue, 13 Apr 2021 15:34:29 -0400 2021-04-21T10:30:00-04:00 2021-04-21T11:30:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
Master's Defense: Ivo Cerda (April 30, 2021 10:00am) https://events.umich.edu/event/83915 83915-21612995@events.umich.edu Event Begins: Friday, April 30, 2021 10:00am
Location: Off Campus Location
Organized By: Biomedical Engineering

Co-registering, chronic, and naturalistic assessments of the electrophysiological and behavioral features of the murine stress response can teach us how stress-behaviors are mechanistically driven by electrophysiological activity in neural circuits, how those relationships change over the course of the multi-week developing response to chronic ongoing stress, and how these changes ultimately contribute to the pathogenesis and progression of major depressive disorder and other psychiatric conditions. However, the long duration and multiplexed nature of the murine stress response have long been barriers to achieving such understandings. To address the need for technology that better captures the time progression of the murine stress response, we engineered the first-ever chronic recording system capable of gathering both behavioral and electrophysiological data in a naturalistic environment for freely-moving mice. Building from previous unpublished work at our lab, we first developed 16 units of a novel photointerrupter-based, Arduino-controlled digital phenotyping system capable of simultaneously recording 50+ behavioral metrics at a sub-second resolution continuously for weeks at a time. Subsequently, with the goal of assisting the concurrent exploration of brain mechanisms and behavior, we engineered a scaffold and cabling structure to support an ultra low-resistance commutator that allows chronic, multi-region brain electrophysiological recordings and integrated it into our digital behavioral phenotyping system. Our novel co-recording system is now fully operational and, along with allowing chronic electrophysiological recordings, supports measures of eating, drinking, food and sugary drink preference (a measure of anhedonia), locomotor activity, sleep, and actigraphy, all the while using 24/7 video tracking to allow detailed classification of behaviors at sub-second resolution. The system is also compatible with standard assessments in the field, including daily weight and fur checks. To demonstrate the duration of its co-recording capabilities, we implanted a cohort of mice with electrodes in three brain regions involved in the murine stress response – olfactory bulb, dorsal hippocampus, and medial prefrontal cortex – and recorded for five weeks. This is the first system to ever produce highly dense behavioral and electrophysiological data simultaneously and continuously over such a period of time.


Details:
DATE: Friday, April 30, 2021
TIME: 10:00 am - 12:00 pm
LOCATION: Zoom https://umich.zoom.us/j/93571968494)
Chair Committee: Brendon Watson, Tim Bruns, Cindy Chestek

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Lecture / Discussion Thu, 29 Apr 2021 20:12:17 -0400 2021-04-30T10:00:00-04:00 2021-04-30T12:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
BME Commencement 2021 (May 1, 2021 3:30pm) https://events.umich.edu/event/83890 83890-21595415@events.umich.edu Event Begins: Saturday, May 1, 2021 3:30pm
Location: Off Campus Location
Organized By: Biomedical Engineering

PLEASE MAKE SURE TO RSVP WITH THE LINK!

BME COMMENCEMENT CEREMONY
SATURDAY, MAY 1, 2021 | 3:30 PM EDT


COMMENCEMENT CEREMONY
ZOOM @ (3:30 PM)

AFTER PARTY
Spatial Chat @ (~4:30 PM)
(AFTER THE CEREMONY)

PROGRAM
Welcome & Introduction | Lonnie Shea Ph.D.
Program Chair Remarks | Rachael Schmedlen, Ph.D., Jan Stegemann, Ph.D., & Tim Bruns, Ph.D.
Program Coordinator Remarks | Rachel Patterson & Maria Steele
Alumni Welcome and Congratulations | Scott Merz, Richard Youngblood, & Xiaotian Tan
Student Addresses | Dipra Debnath, Ivo Woldarsky, & Katy Norman
Announcing the Graduates | Melissa Wrobel Ph.D., Brendon Baker, Ph.D., James Weiland, Ph.D., & Tim Bruns, Ph.D.
Confirmation of Degrees | Lonnie Shea, Ph.D.
Congratulations and Closing | Lonnie Shea, Ph.D.
Virtual socializing & After Party | Come congratulate and socialize with your fellow graduates, families, professors, and friends following the BME Commencement Ceremony.

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Ceremony / Service Tue, 27 Apr 2021 15:09:45 -0400 2021-05-01T15:30:00-04:00 Off Campus Location Biomedical Engineering Ceremony / Service BME Logo
RNA Seminar featuring: Olivia Rissland, University of Colorado School of Medicine (May 3, 2021 4:00pm) https://events.umich.edu/event/81302 81302-20881902@events.umich.edu Event Begins: Monday, May 3, 2021 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

Registration Required: https://umich.zoom.us/webinar/register/WN_vA9zYS5nSEenf8Zmt1f-qA


ABSTRACT: The maternal-to-zygotic transition (MZT) is a conserved step in animal development, where control is passed from the maternal to the zygotic genome. Although the MZT is typically considered from its impact on the transcriptome, we previously found that three maternally deposited Drosophila RNA binding proteins (ME31B, Trailer Hitch [TRAL], and Cup) are also cleared during the MZT by unknown mechanisms. Here, we show that these proteins are degraded by the ubiquitin-proteasome system. Marie Kondo, an E2 conjugating enzyme, and the E3 CTLH ligase are required for the destruction of ME31B, TRAL, and Cup. Structure modeling of the Drosophila CTLH complex suggests that substrate recognition is different than orthologous complexes. Despite occurring hours earlier, egg activation mediates clearance of these proteins through the Pan Gu kinase, which stimulates translation of Kondo mRNA. Clearance of the maternal protein dowry thus appears to be a coordinated, but as-yet underappreciated, aspect of the MZT.

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Lecture / Discussion Fri, 02 Apr 2021 16:07:11 -0400 2021-05-03T16:00:00-04:00 2021-05-03T17:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Olivia Rissland, Ph.D.
PhD Defense: Jonas Schollenberger (May 4, 2021 3:00pm) https://events.umich.edu/event/83855 83855-21555868@events.umich.edu Event Begins: Tuesday, May 4, 2021 3:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Cerebrovascular occlusive disease (CVOD) is a major risk factor for ischemic stroke and is characterized by the presence of stenosis in the arteries supplying the brain. The cerebral vasculature has an innate ability to compensate for flow reductions, caused by the presence of CVOD, through a network of collateral pathways in the circle of Willis (CoW). However, flow compensation is highly patient-specific and dependent on the cerebral vasculature anatomy, availability of collateral pathways, degree of stenosis and, the condition of the cerebral microcirculation and its autoregulatory response. Unfortunately, clinically available imaging tools only provide limited information on flow compensation and the underlying cerebral hemodynamics. Given the complexity of the cerebral vasculature, better tools are necessary to characterize cerebral hemodynamics and guide the risk assessment of ischemic stroke.



Image-based computational fluid dynamics (CFD) provides a powerful tool for non-invasively analyzing cerebral hemodynamics with high spatial and temporal resolutions. However, CFD modeling of cerebral hemodynamics is challenging due to the need for patient-specific data to calibrate outflow boundary conditions in the brain. In this thesis, we explore a novel strategy to quantitatively characterize cerebral hemodynamics using CFD in combination with tissue perfusion from arterial spin labeling (ASL) MRI.



Firstly, we quantified territorial perfusion in the cerebral circulation through implementing and optimizing a vessel-selective arterial spin labeling (VS-ASL) sequence. VS-ASL is generally limited by its low labeling efficiency causing poor signal-to-noise ratio. We investigated the effects of off‐resonance, pulsatility, and vessel movement, and evaluated methods to maximize labeling efficiency and overall image quality. We found that an off-resonance calibration scan in combination with cardiac-triggering significantly improved labeling efficiency and image quality. Vessel movement during the MRI protocol occurred in the majority of study subjects and needs to be accounted for to maximize labeling efficiency.



Secondly, we developed a strategy to calibrate patient-specific CFD models of cerebral blood flow. The calibration consisted of estimating the total inflow to the CoW from PC-MRI and the flow splits in the CoW from non-selective ASL perfusion images. The outflow boundary conditions were iteratively tuned to match the estimated flow splits, and the ASL-calibrated CFD model was then validated against territorial perfusion maps from VS-ASL by calculating the blood supply to each cerebral territory using Lagrangian particle tracking (LPT). We found an overall good match in a small group of subjects; particularly, the flow compensation between hemispheres was captured well by the calibrated CFD models.



Thirdly, we investigated the impact of two outflow boundary condition strategies, an ASL-based and allometric-based calibration, on cerebral hemodynamics. The ASL-based calibrated CFD analysis captured the flow compensation between hemispheres as measured with VS-ASL and lead to an approximately symmetrical flow distribution in the CoW. In contrast, the allometric-based calibrated CFD analysis was unable to capture the collateral flow compensation, which resulted in large differences in flow between hemispheres.



Finally, the clinical feasibility and capabilities of our proposed CFD analysis was demonstrated in two CVOD patients. The CFD analysis showed significant differences in cerebral hemodynamics between the patients despite similar degrees of stenosis severity, highlighting the importance of a patient-specific assessment. Comparison of pre-operative and post-operative hemodynamics in one patient resulted in only minor changes following revascularization despite severe carotid stenosis. We demonstrated that our CFD analysis can provide detailed and quantitative information about hemodynamic impact of carotid stenosis and collateral flow compensation in the circle of Willis.


Date: Tuesday, May 4, 2021

Time: 3:00 PM

Zoom: https://umich.zoom.us/j/93059726229 (Zoom link requires prior registration)

Co-Chairs: Dr. C. Alberto Figueroa and Dr. Luis Hernandez-Garcia

For Assistance or Questions
um-bme@umich.edu

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Lecture / Discussion Thu, 22 Apr 2021 13:33:46 -0400 2021-05-04T15:00:00-04:00 2021-05-04T16:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Elissa Welle (May 7, 2021 10:00am) https://events.umich.edu/event/83883 83883-21587612@events.umich.edu Event Begins: Friday, May 7, 2021 10:00am
Location: Off Campus Location
Organized By: Biomedical Engineering

Neural interfaces create a connection between neural structures in the body and external electronic devices. Brain-machine interfaces and bioelectric medicine therapies rely on the seamless integration of neural interfaces with the brain, nerves, or spinal cord. However, conventional neural interfaces cannot meet the demands of high channel count, signal fidelity, and signal longevity that these applications require.



In this thesis we characterized the damage resulting from conventional Utah arrays after multiple years of implantation in the cortex of a non-human primate. The neuron density around the electrode shanks was compared to the neuron density of nearby healthy tissue, finding a 73% loss in density around the electrodes. The explanted arrays were imaged and characterized for forms of electrode surface inconsistency. Coating cracks, tip breakage, and parylene cracks were the most common inconsistency. A significantly higher number of tip breakage and coating crack occurrences were found on the edges of the arrays as compared to the middle. In this work, we made clear the need for a minimally damaging alternative to the Utah electrode array.



Neural interfaces composed of carbon fiber electrodes, with a diameter of 6.8 microns, could enable a more seamless integration with the body. Previous work resulted in an array of individuated carbon fiber electrodes that could record reliably high signal-to-noise ratio neural signals from the brain for several months. However, the carbon fiber arrays were limited by only 30% of the electrodes recording neural signals, despite inducing very minimal inflammation. Additionally, it was relatively unknown if carbon fibers would make suitable long-term peripheral neural interfaces. Here, we illustrate the potential of carbon fiber electrodes to meet the needs of a variety of neural applications.



First, we optimized state-of-the-art carbon fiber electrodes to reliably record single unit electrophysiology from the brain. By analyzing the previous manufacturing process, the cause of the low recording yield of the carbon fiber arrays was identified as the consistency of the electrode tip. A novel laser cutting technique was developed to produce a consistent carbon fiber tip geometry, resulting in a near tripling of recording yield of high amplitude chronic neural signals. The longevity of the carbon fiber arrays was also addressed. The conventional polymer coating was compared against platinum iridium coating and an oxygen plasma treatment, both of which outperformed the polymer coating. In this work, we customized carbon fiber electrodes for reliable, long-term neural recording.



Secondly, we translated the carbon fiber technology from the brain to the periphery in an architecture appropriate for chronic implantation. The insertion of carbon fibers into the stiffer structures in the periphery is enabled by sharpening the carbon fibers. The sharpening process combines a butane flame to sharpen the fibers with a water bath to protect the base of the array. Sharpened carbon fibers recorded electrophysiology from the rat vagus nerve and feline dorsal root ganglia, both structures being important targets for bioelectric medicine therapies. The durability of carbon fibers was also displayed when partially embedded carbon fibers in medical-grade silicone withstood thousands of repeated bends without fracture. This work showed that carbon fibers have the electrical and structural properties necessary for chronic application.



Overall, this work highlights the vast potential of carbon fiber electrodes. Through this thesis, future brain-machine interfaces and bioelectric medicine therapies may utilize sub-cellular electrodes such as carbon fibers in medical applications.



Date: Friday, May 7, 2021

Time: 10:00 AM

Zoom: https://umich.zoom.us/j/95839545566 (Zoom link requires prior registration)

Chair: Dr. Cynthia Chestek

For Assistance or Questions
um-bme@umich.edu

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Lecture / Discussion Mon, 26 Apr 2021 17:03:39 -0400 2021-05-07T10:00:00-04:00 2021-05-07T11:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
2021 BME Symposium (May 10, 2021 12:00pm) https://events.umich.edu/event/82858 82858-21203302@events.umich.edu Event Begins: Monday, May 10, 2021 12:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

To register please see:
https://myumi.ch/r8GzZ

The 2021 BME symposium will showcase our work in the areas of Imaging, Neural Engineering, Regenerative Medicine, and Precision Health. The event will take place over two days in the afternoons of Monday, May 10, 12:00 PM - 5:00 PM, and Tuesday, May 11, 12:00 PM - 5:00 PM. Each afternoon will include faculty talks, mini student dissertations, a panel discussion, and student poster sessions.

The goal of this event is to bring together faculty and students affiliated with BME from all parts of campus as a step toward building the BME community and celebrating accomplishments through difficult times while having an eye toward the future.

Please sign up and join us!

2021 U-M BME Symposium



May 10, 2021: 12:00 PM - 5:00 PM


Imaging at UM

May 10, 2021 - 12:00pm - 1:30pm
Location: Virtual/Zoom
Livestream Available (Visible After Registration)

Moderator: Doug Noll
12:00 - 12:15 - Zhongming Liu, “Preclinical MRI of brain-gut interactions”
12:15 - 12:30 - Nicole Seiberlich, “Translating Quantitative MRI to the Clinic”
12:30 - 12:45 - Yannis Paulus, “Multimodal Photoacoustic Microscopy, OCT, and Fluorescence Molecular and Cellular Imaging of the Retina”
12:45 - 1:05 - Student Dissertations
1:05 - 1:30 - Panel Discussion - “The Future of Imaging Research at Michigan” - Vikas Gulani, Jeff Fessler, Cheri Deng, Zhen Xu, Xueding Wang


Neural Engineering at UM

May 10, 2021 - 2:00pm - 3:30pm
Location: Virtual/Zoom
Livestream Available (Visible After Registration)

Moderator: Jim Weiland
2:00 - 2:15 - Kamran Diba, TBD
2:15 - 2:30 - Scott Lempka, TBD
2:30 - 2:45 - Deanna Gates, TBD
2:45 - 3:05 - Student Dissertations
3:05 - 3.30 - Panel Discussion - “The Science Fiction Future of Neural Engineering” - Cindy Chestek, Parag Patil, Tim Bruns, Bill Stacey


Poster Session: Imaging & Neural Engineering

May 10, 2021 - 4:00pm - 5:00pm
Location: Virtual/Spatial Chat

This poster session will give BME students a chance to present and discuss their research in the areas of Imaging and Neural Engineering.


May 11, 2021: 12:00 PM - 5:00 PM


Regenerative Medicine at UM

May 11, 2021 - 12:00pm - 1:30pm
Location: Virtual/Zoom
Livestream Available (Visible After Registration)

Moderator: Lonnie Shea
12:00 - 12:15 - Carlos Aguilar, ”Understanding & Re-Writing Stem Cell Programs to Live Forever.”
12:15 - 12:30 - Idse Heemskerk, “Predicting cell fate from signaling history in human pluripotent stem cells”
12:30 - 12:45 - Ariella Shikanov, TBD
12:45 - 1:05 - Student Dissertations
1:05 - 1:30 - Panel Discussion - "Grand Challenges in Regenerative Medicine" - Dave Kohn


Precision Health at UM

May 11, 2021 - 2:00pm - 3:30pm
Location: Virtual/Zoom
Livestream Available (Visible After Registration)

Moderator: TBD
2:00 - 2:15 - Sriram Chandrasekharan, TBD
2:15 - 2: 30 - James Moon, TBD
2:30 - 2:45 - Deepak Nagrath, TBD
2:45 - 3:05 - Student Dissertations
3:05 - 3:30 - Panel Discussion - "Hope or Hype for Treating Diseases" - James Moon, Sriram Chandrasekharan, Deepak Nagrath



Poster Session: Regenerative Medicine & Precision Health


May 11, 2021 - 4:00pm - 5:00pm
Location: Virtual/Spatial Chat


This poster session will give BME students a chance to present and discuss their research in the areas of Regenerative Medicine and Precision Health.

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Conference / Symposium Thu, 22 Apr 2021 13:38:37 -0400 2021-05-10T12:00:00-04:00 2021-05-10T17:00:00-04:00 Off Campus Location Biomedical Engineering Conference / Symposium BME Logo
2021 BME Symposium (May 11, 2021 12:00pm) https://events.umich.edu/event/82858 82858-21555869@events.umich.edu Event Begins: Tuesday, May 11, 2021 12:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

To register please see:
https://myumi.ch/r8GzZ

The 2021 BME symposium will showcase our work in the areas of Imaging, Neural Engineering, Regenerative Medicine, and Precision Health. The event will take place over two days in the afternoons of Monday, May 10, 12:00 PM - 5:00 PM, and Tuesday, May 11, 12:00 PM - 5:00 PM. Each afternoon will include faculty talks, mini student dissertations, a panel discussion, and student poster sessions.

The goal of this event is to bring together faculty and students affiliated with BME from all parts of campus as a step toward building the BME community and celebrating accomplishments through difficult times while having an eye toward the future.

Please sign up and join us!

2021 U-M BME Symposium



May 10, 2021: 12:00 PM - 5:00 PM


Imaging at UM

May 10, 2021 - 12:00pm - 1:30pm
Location: Virtual/Zoom
Livestream Available (Visible After Registration)

Moderator: Doug Noll
12:00 - 12:15 - Zhongming Liu, “Preclinical MRI of brain-gut interactions”
12:15 - 12:30 - Nicole Seiberlich, “Translating Quantitative MRI to the Clinic”
12:30 - 12:45 - Yannis Paulus, “Multimodal Photoacoustic Microscopy, OCT, and Fluorescence Molecular and Cellular Imaging of the Retina”
12:45 - 1:05 - Student Dissertations
1:05 - 1:30 - Panel Discussion - “The Future of Imaging Research at Michigan” - Vikas Gulani, Jeff Fessler, Cheri Deng, Zhen Xu, Xueding Wang


Neural Engineering at UM

May 10, 2021 - 2:00pm - 3:30pm
Location: Virtual/Zoom
Livestream Available (Visible After Registration)

Moderator: Jim Weiland
2:00 - 2:15 - Kamran Diba, TBD
2:15 - 2:30 - Scott Lempka, TBD
2:30 - 2:45 - Deanna Gates, TBD
2:45 - 3:05 - Student Dissertations
3:05 - 3.30 - Panel Discussion - “The Science Fiction Future of Neural Engineering” - Cindy Chestek, Parag Patil, Tim Bruns, Bill Stacey


Poster Session: Imaging & Neural Engineering

May 10, 2021 - 4:00pm - 5:00pm
Location: Virtual/Spatial Chat

This poster session will give BME students a chance to present and discuss their research in the areas of Imaging and Neural Engineering.


May 11, 2021: 12:00 PM - 5:00 PM


Regenerative Medicine at UM

May 11, 2021 - 12:00pm - 1:30pm
Location: Virtual/Zoom
Livestream Available (Visible After Registration)

Moderator: Lonnie Shea
12:00 - 12:15 - Carlos Aguilar, ”Understanding & Re-Writing Stem Cell Programs to Live Forever.”
12:15 - 12:30 - Idse Heemskerk, “Predicting cell fate from signaling history in human pluripotent stem cells”
12:30 - 12:45 - Ariella Shikanov, TBD
12:45 - 1:05 - Student Dissertations
1:05 - 1:30 - Panel Discussion - "Grand Challenges in Regenerative Medicine" - Dave Kohn


Precision Health at UM

May 11, 2021 - 2:00pm - 3:30pm
Location: Virtual/Zoom
Livestream Available (Visible After Registration)

Moderator: TBD
2:00 - 2:15 - Sriram Chandrasekharan, TBD
2:15 - 2: 30 - James Moon, TBD
2:30 - 2:45 - Deepak Nagrath, TBD
2:45 - 3:05 - Student Dissertations
3:05 - 3:30 - Panel Discussion - "Hope or Hype for Treating Diseases" - James Moon, Sriram Chandrasekharan, Deepak Nagrath



Poster Session: Regenerative Medicine & Precision Health


May 11, 2021 - 4:00pm - 5:00pm
Location: Virtual/Spatial Chat


This poster session will give BME students a chance to present and discuss their research in the areas of Regenerative Medicine and Precision Health.

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Conference / Symposium Thu, 22 Apr 2021 13:38:37 -0400 2021-05-11T12:00:00-04:00 2021-05-11T17:00:00-04:00 Off Campus Location Biomedical Engineering Conference / Symposium BME Logo
RNA Seminar featuring: Thomas Martinez, Salk Institute for Biological Studies (May 17, 2021 4:00pm) https://events.umich.edu/event/81303 81303-20881903@events.umich.edu Event Begins: Monday, May 17, 2021 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

Registration Required: https://umich.zoom.us/webinar/register/WN_90RkcQTGQZa7ifQ8kbSdNQ

KEYOWORDS: microprotein, smORF, ribosome profiling

ABSTRACT: Functional protein-coding small open reading frames (smORFs) are emerging as an important class of genes. Several smORF-encoded microproteins have been characterized and implicated in a variety of critical processes, including regulation of mRNA decay, DNA repair, and muscle formation. Thus, rigorous and comprehensive annotation of protein-coding smORFs is critical to our understanding of basic biology and physiology, as well as disease. We recently developed an improved workflow that integrates de novo transcriptome assembly and ribosome profiling to overcome obstacles with previous methods to more confidently annotate thousands of novel smORFs across multiple human cell lines, including hundreds encoded on putative non-coding RNAs. Over 1,500 smORFs are found in two or more cell lines, and ~40% lack a canonical AUG start codon. Evolutionary conservation analyses suggest that hundreds of smORF-encoded microproteins are likely functional. We also find that smORF-derived peptides are detectable on human leukocyte antigen complexes, positioning smORFs as a source of novel antigens. The annotation of protein-coding smORFs radically alters the current view of the human genome’s coding capacity and will provide a rich pool of unexplored, functional human genes.

BIO: Thomas received his B.S. in Biological Engineering from MIT and trained in Prof. JoAnne Stubbe’s laboratory, where he studied the mechanism of ribonucleotide reductase. He then recieved his Ph.D. in Biochemistry & Molecular Biophysics from Caltech as an NIH NRSA predoctoral fellow under the mentorship of Prof. Peter Dervan. His thesis work focused primarily on characterizing the effects of DNA binding pyrrole-imidazole polyamides on DNA replication in prostate cancer cells. Thomas is currently an NIH NRSA postdoctoral fellow in Prof. Alan Saghatelian’s laboratory, where he has developed an integrative platform combining ribosome profiling and de novo transcriptome assembly to discover functional smORF encoded microproteins in the human genome.

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Lecture / Discussion Wed, 14 Apr 2021 12:39:54 -0400 2021-05-17T16:00:00-04:00 2021-05-17T17:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Thomas Martinez, Salk Institute for Biological Studies
PhD Defense: Edward Peter Washabaugh IV (May 27, 2021 10:00am) https://events.umich.edu/event/84050 84050-21619709@events.umich.edu Event Begins: Thursday, May 27, 2021 10:00am
Location: Off Campus Location
Organized By: Biomedical Engineering

Injuries to the neuromusculoskeletal systems often result in muscle weakness, abnormal coordination strategies, and gait impairments. Functional resistance training during walking—where a patient walks while a device increases loading on the leg—is an emerging approach to combat these symptoms. While simple passive devices (i.e., ankle weights and resistance bands) can be applied for this training, rehabilitation robots have more potential upside because they can be controlled to treat multiple gait abnormalities and can be monitored by clinicians. However, the cost of conventional robotic devices limits their use in the clinical or home setting. Hence, in this dissertation, we designed, developed, and tested passive and semi-passive wearable exoskeleton devices as a low-cost solution for providing controllable/configurable functional resistance training during walking.


We developed and tested two passive exoskeleton devices for providing resistance to walking and tested their effects on able-bodied participants and stroke survivors. First, we created a patented device that used a passive magnetic brake to provide a viscous (i.e., velocity-dependent) resistance to the knee. The resistive properties of the device could be placed under computer control (i.e., made semi-passive) to control resistance in real-time. Next, we created a passive exoskeleton that provided an elastic (i.e., position-dependent) resistance. While not controllable, this device was highly configurable. Meaning it could be used to provide resistance to joint flexion, extension, or to both (i.e., bidirectionally). Human subjects testing with these devices indicated they increased lower-extremity joint moments, powers, and muscle activation during training. Training also resulted in significant aftereffects—a potential indicator of therapeutic effectiveness—once the resistance was removed. A separate experiment indicated that individuals often kinematically slack (i.e., reduce joint excursions to minimize effort) when resistance is added to the limb. We also found that providing visual feedback of joint angles during training significantly increased muscle activation and kinematic aftereffects (i.e., reduced slacking).


With passive devices, the type of passive element used largely dictates the muscle groups, types of muscle contraction, joint actions, and the phases of gait when a device is able to apply resistance. To examine this issue, we compared the training effects of viscous and elastic devices that provided bidirectional resistance to the knee during gait. Additionally, we compared training with viscous resistances at the hip and knee joints. While the resistance type and targeted joint altered moments, powers, and muscle activation patterns, these methods did not differ in their ability to produce aftereffects, alter neural excitability, or induce fatigue in the leg muscles. While this may indicate that the resistance type does not have a large effect on functional resistance training during walking, it is possible that an extended training with these devices could produce a different result.


Lastly, we used musculoskeletal modeling in OpenSim to directly compare several strategies that have been used to provide functional resistance training to gait in the clinic or laboratory setting. We found that devices differed in their ability to alter gait parameters during walking. Hence, these findings could help clinicians when selecting a resistive strategy for their patients, or engineers when designing new devices or control schemes.



Date: Thursday, May 27, 2021

Time: 10:00 AM

Zoom: https://umich.zoom.us/meeting/register/tJIufumrrDgtHd3z5Jg3Y_BG4ZC70OPrjTjk (Zoom link requires prior registration)

Chair: Dr. Chandramouli Krishnan

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Lecture / Discussion Fri, 14 May 2021 13:49:26 -0400 2021-05-27T10:00:00-04:00 2021-05-27T11:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: William Y. Wang (June 4, 2021 12:30pm) https://events.umich.edu/event/84102 84102-21620248@events.umich.edu Event Begins: Friday, June 4, 2021 12:30pm
Location: Off Campus Location
Organized By: Biomedical Engineering

Mechanoreciprocity in cell migration is an emerging concept describing the dynamic, bi-directional interactions between migrating cells and the surrounding extracellular matrix (ECM) they negotiate. Migrating cells not only sense and adapt to biochemical and biophysical ECM cues, but also, exert forces, deposit matrix, and secrete chemokines, matrix metalloproteinases, and matrix crosslinking enzymes that dynamically alter the same ECM properties known to regulate cell migration. Due to limitations in standard cell migration assays, how matrix properties influence cell migration and in turn, how cells influence matrix properties, has previously been studied as separate processes. However, observations from development, wound healing, and a variety of disease processes highlight the interdependency and iterative relationship between cell migration and ECM. An improved understanding of the underlying mechanisms that orchestrate the coevolution of migrating cells and ECM will aid in tissue engineering and regenerative medicine efforts to guide repair fibroblasts to regenerate wound beds, direct collective endothelial cell migration to vascularize ischemic or engineered tissue grafts and confine otherwise metastatic cancer cells to the primary tumor. Thus, the focus of this dissertation is to design biomimetic microsystems that afford investigation of cell migration mechanoreciprocity with a focus on fibroblasts, endothelial cells, and cancer cells.



First, this thesis investigated how single mesenchymal cells (fibroblasts and cancer cells) migrate in fibrous stromal tissue settings, such as in trans-stromal cancer cell migration during metastasis. To model fibrous stromal tissue, 3D fiber networks were electrospun over microfabricated wells to define ECM mechanics. Independently tuning alignment and stiffness of these matrices resulted in two phenotypically distinct cell migration modes. In contrast to stiff matrices where cells migrated continuously in a traditional mesenchymal fashion, cells in deformable matrices stretched matrix fibers to store elastic energy; subsequent adhesion failure triggered sudden matrix recoil and rapid cell translocation (termed slingshot migration). Across a variety of cell types, traction force measurements revealed a relationship between cell contractility and the matrix stiffness where slingshot migration mode occurred optimally.



Next, this thesis describes how microenvironmental cues influence collective endothelial cell migration during sprouting angiogenesis towards the design of pro-angiogenic biomaterials. This work employed a multiplexed angiogenesis-on-a-chip platform to assess the chemokine-directed 3D invasion of endothelial cells from a lumenized parent vessel into user-defined ECM. By tuning soluble and physical cues of the ECM, this work identified how 1) functional angiogenesis requires microenvironmental cues that balance cell invasion speed and proliferation; 2) dynamic interactions between sprout stalk cells and ECM regulates neovessel lumenization; and 3) imbuing microporosity within synthetic hydrogels can enhance endothelial cell invasion and angiogenic sprout lumenization.



Lastly, this thesis investigated how fibrous matrix cues activate quiescent vessel-lining endothelial cells into invasive tip cells in the context of fibrosis. Composite hydrogels (electrospun fiber segments suspended within 3D ECM) were integrated with the angiogenesis-on-a-chip platform. These studies establish that heightened matrix fiber density destabilizes cell-cell adherens junctions, reduces endothelium barrier function, and promotes the invasion of endothelial tip cells. Performing transcriptomic and secretomic analyses on fiber-induced tip endothelial cells revealed that fibrous ECM cues promote a fibrosis propagating phenotype.



Overall, the work presented in this dissertation integrates tunable biomaterials with microfabricated devices to investigate cell migration mechanoreciprocity of single mesenchymal cell migration, the collective migration of endothelial cells during angiogenesis, and endothelial-mesenchymal transition of quiescent endothelial cells into a fibrosis propagating cell phenotype.



Date: Friday, June 4, 2021

Time: 12:30 PM

Zoom: https://umich.zoom.us/meeting/register/tJcsf-uhpj4vGtyM7x-td2VV39BzqmF_zoob (Zoom link requires prior registration)

Chair: Dr. Brendon Baker

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Lecture / Discussion Mon, 24 May 2021 14:17:02 -0400 2021-06-04T12:30:00-04:00 2021-06-04T13:30:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
RNA Innovation Seminar featuring Rising Scholars: Khan & McMillan (June 14, 2021 4:00pm) https://events.umich.edu/event/83934 83934-21619166@events.umich.edu Event Begins: Monday, June 14, 2021 4:00pm
Location: Off Campus Location
Organized By: Center for RNA Biomedicine

Registration Required: https://umich.zoom.us/webinar/register/WN_uLz-ONHVQPuRINMYUNvBJQ

“CCR5 as a model to examine reporter assays in evaluating translational phenomena”
Yousuf Khan
Knight-Hennessy Scholar
Stanford University

KEYWORDS: dual luciferase, frameshifting, recoding, CCR5
ABSTRACT: During the decoding of a subset of mRNAs, a proportion of ribosomes productively shift to the −1 reading frame at specific slippage-prone sites in a phenomenon known as programmed −1 ribosomal frameshifting (−1 PRF) to generate a frameshifted, C-terminally unique protein. The first experimentally verified occurrence of functionally utilized non-retroelement derived −1 PRF in humans has been reported in the mRNA encoding the immune-functioning C-C chemokine receptor 5 (CCR5). Here, we show that frameshifting does not occur during CCR5 decoding. Apart from its importance in understanding expression of a gene relevant to cancer, an HIV-1 receptor (and the associated claimed rationale for generating the first humans derived from genetically modified embryos), the findings imply that caution is appropriate in assessing results from translational reporter assays.

~and~

“Intersection between RNA methylation and TDP43-mediated toxicity in ALS”
Michael McMillan
Ph.D. candidate
Cellular and Molecular Biology
University of Michigan

KEYWORDS: TDP43, m6A, ALS, RNA stability
ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease resulting in the death of upper and lower motor neurons. ALS has no known cure and limited therapeutic options, and the underlying pathological mechanisms remain unclear. Despite considerable variability in clinical presentation, over 95% of ALS cases exhibit cytoplasmic inclusions of the RNA binding protein TDP43. Emerging evidence suggests that TDP43 is crucial for RNA stability, and that dysregulation of RNA homeostasis may contribute to ALS pathogenesis.
Methylation of RNA at the 6th position nitrogen (N6-methyladenosine methylation, or m6A) by methyltransferases (writers) or removal of methyl groups by demethylases (erasers) has dramatic effects on RNA stability and translation mediated by a family of RNA biding proteins that recognize methylated RNA (readers). m6A writers and erasers specifically localize to nuclear speckles, membraneless nuclear organelles rich in RNA binding proteins and splicing factors, including TDP43. Together with our data showing that TDP43 regulates RNA stability, these observations suggest that TDP43 may destabilize m6A modified RNA. Here, we show that methylated RNA co-purified with TDP43 from cultured cells via RNA immunoprecipitation, and abrogation of methylation sites disrupted TDP43 binding, suggesting that TDP43 recognizes m6A modified RNA in cellulo. We also noted profound and widespread hypermethylation of coding and non-coding transcripts in ALS spinal cord, many overlapping with confirmed TDP43 target transcripts. Consistent with a central role for m6A modification in TDP43-mediated toxicity, we identified several factors operating within the m6A pathway that enhance or suppress the toxicity of TDP43 in rodent primary cortical neurons via a single-cell CRISPR/Cas9 candidate-based screen. Genetic knockout of the established m6A reader YTHDF2 rescued TDP43 toxicity in primary neurons, and YTHDF2 was also upregulated in ALS postmortem sections. Together, these data imply a fundamental link between m6A RNA modifications and ALS pathogenesis, potentially mediated by TDP43-dependent RNA destabilization.

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Lecture / Discussion Tue, 18 May 2021 14:31:45 -0400 2021-06-14T16:00:00-04:00 2021-06-14T17:00:00-04:00 Off Campus Location Center for RNA Biomedicine Lecture / Discussion Yousuf Khan (Stanford) & Mike McMillan (U-M)
UM Single Cell Spatial Analysis Program (SCSAP) Kickoff Symposium (June 22, 2021 1:00pm) https://events.umich.edu/event/84222 84222-21620781@events.umich.edu Event Begins: Tuesday, June 22, 2021 1:00pm
Location: Off Campus Location
Organized By: Single Cell Spatial Analysis Program (SCSAP)

The UM BSI SINGLE CELL SPATIAL ANALYSIS PROGRAM KICK OFF SYMPOSIUM

Featuring Keynote Speaker Tzumin Lee, M.D. PhD.
Presenting: Linking single-cell genomics with single-cell genetics.

Date: June 22nd
Time: 1:00 pm -4:30 PM EST
Location: Zoom Webinar
Register at: https://umich.zoom.us/webinar/register/WN_Zax2iT5TReGILR_sQmIZ3w

Additional Mini-talks on: Spatial Transcriptomics, Single Cell RNA-Seq, CyTOF, Multispectral Imaging, Seq-SCOPE, Rare Cell Isolation.

Speakers:
Roger Cone, Ph.D. Evan Keller, Ph.D.
Thomas Wilson, M.D., Ph.D. Jun Li, Ph.D.
Tim Frankel, M.D. Sue Hammoud, Ph.D.
Jun Hee Lee, Ph.D. Olivia Koues, Ph.D.
Sunitha Nagrath, Ph.D. Justin Colacino, Ph.D.
Arvind Rao, Ph.D. Max S. Wicha, M.D.
Patricia Schnepp, Ph.D.

Find us at https://singlecellspatialanalysis.umich.edu
Questions/Comments please contact us at singlecellspatialanalysis@umich.edu

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Workshop / Seminar Fri, 04 Jun 2021 13:26:44 -0400 2021-06-22T13:00:00-04:00 2021-06-22T16:30:00-04:00 Off Campus Location Single Cell Spatial Analysis Program (SCSAP) Workshop / Seminar Dr. Tzumin Lee
PhD Defense: Jiayue Cao (June 23, 2021 3:00pm) https://events.umich.edu/event/84287 84287-21621035@events.umich.edu Event Begins: Wednesday, June 23, 2021 3:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

The stomach and brain interact closely with each other. Their interactions are central to digestive functions and the “gut feeling”. The neural pathways that mediate the stomach-brain interactions include the vagus nerve and the thoracic nerve. Through these nerves, the stomach can relay neural signals to a number of brain regions that span a central gastric network. This gastric network allows the brain to monitor and regulate gastric physiology and allows the stomach to influence emotion and cognition. Impairment of this gastric network may lead to both gastric and neurological disorders, e.g., anxiety, gastroparesis, functional dyspepsia, and obesity. However, the structural constituents and functional roles of the central gastric network remain unclear. In my dissertation research, I leveraged complementary techniques to characterize the central gastric network in rats across a wide range of scales and different gastric states. In animal experiments, I used functional magnetic resonance imaging (fMRI) to map brain activity synchronized with gastric electrical activity and to map brain activations induced by electrical stimulation applied to the cervical vagus or its afferent terminals on the stomach. I also used neurophysiology to characterize gastric neurons in brainstem in response to gastric electrical stimulation. Results from my studies suggest that 1) gastric neurons in the brainstem are selective to the orientation of muscle activity relayed through intramuscular arrays, 2) the central gastric network is intrinsically coupled to gastric slow waves and their amplitude fluctuations primarily via vagal signaling, 3) selective stimulation of the vagus can evoke widespread and fast brain responses and alter functional connectivity within and beyond the central gastric network. My dissertation research contributes to the foundation of mapping and characterizing the central and peripheral mechanisms of gastric interoception and sheds new light on where and how to stimulate the peripheral nerves to modulate stomach-brain interactions.



Date: Wednesday, June 23, 2021

Time: 3:00 PM

Zoom: https://umich.zoom.us/j/2757414653

Chair: Dr. Zhongming Liu

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Lecture / Discussion Tue, 15 Jun 2021 23:04:33 -0400 2021-06-23T15:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Eric Charles Hobson (June 24, 2021 10:30am) https://events.umich.edu/event/84237 84237-21620794@events.umich.edu Event Begins: Thursday, June 24, 2021 10:30am
Location: Off Campus Location
Organized By: Biomedical Engineering

Mechanical testing of viscoelastic biomaterials is of critical importance in biomedical engineering, enabling basic research into the role of the extracellular matrix, investigatory and diagnostic testing of tissues and biofluids, and the development and characterization of tissue engineered therapeutics. Conventional material testing approaches used for soft biomaterials generally require force application through direct contact with a sample, leading to potential contamination and damage, and thereby limiting these approaches to end-point measurements. To overcome these limitations, we have developed a new measurement technique, Resonant Acoustic Rheometry (RAR), which enables high-throughput, quantitative, and non-contact viscoelastic characterization of biomaterials, soft tissues, and biological fluids.



RAR uses ultrasonic pulses to both generate microscale perturbations and measure the resulting resonant oscillations at the surface of soft materials using standard labware. Resonant oscillatory properties obtained from the frequency spectra of the surface oscillations, including the resonant frequency and the damping coefficient, are used to quantify material properties such as shear modulus, shear viscosity, and surface tension in both viscoelastic solids and liquids.



We developed a prototype RAR system and tested it on a range of soft biomaterials, with shear moduli ranging from under 100 Pa to over 50 kPa, including fibrin, gelatin, and polyethylene glycol (PEG). Shear moduli measured using RAR were validated both computationally using finite element analysis and experimentally using conventional shear rheometry, with excellent linear correlation in measured elasticity between techniques (R2 > 0.95). By performing parallel RAR experiments using microwells of different sizes, we verified that resonant oscillatory behaviors could be used to quantify the intrinsic viscoelastic properties of a material. We also demonstrated the rapid, non-contact monitoring of changes in material properties over a variety of temporal scales, ranging from processes occurring on the order of milliseconds to those occurring over hours and days. High temporal resolution RAR measurements, with sampling intervals as low as 0.2 seconds, were used to characterize the gelation process. Characteristic features of the resonant surface waves during phase transition were applied to identify the gel point for various hydrogels. High sample throughput was demonstrated by performing longitudinal RAR testing to explore the impact of hydrogel polymer and crosslinker concentration on both reaction kinetics and final mechanical properties in full factorial experiments consisting of over 15,000 unique measurements. We were able to identify individual effects of design parameters as well as interactions that led to unexpected mechanical properties, demonstrating the importance of combinatorial methods and high-throughput mechanical characterization in material design.



These studies demonstrate that RAR can rapidly and accurately assess the mechanical properties of soft viscoelastic biomaterials. The measurements generated are analogous to those produced using conventional mechanical testing, and RAR is further capable of longitudinal viscoelastic studies over time. RAR applies automation in both data collection and analysis, allowing high throughput measurement of an array of samples without contact or the need for manual intervention. Furthermore, RAR uses standard microwell plates, which simplifies sample preparation and handling. The viscoelastic properties of soft biomaterials are relevant in a wide range of applications, including for clinical diagnostic assays and the development of hydrogel materials for regenerative medicine. RAR represents a fast, accurate, and cost-effective method for materials characterization in these applications.



June 24 - 10:30 AM

Zoom: https://umich.zoom.us/meeting/register/tJcsd-iurTosGdNn_gR-FbOCe5TUR09Y58WV

Co-Chairs: Dr. Cheri Deng and Dr. Jan Stegmann

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Lecture / Discussion Tue, 22 Jun 2021 16:37:33 -0400 2021-06-24T10:30:00-04:00 2021-06-24T11:30:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Hans Zander (July 9, 2021 9:00am) https://events.umich.edu/event/84346 84346-21623406@events.umich.edu Event Begins: Friday, July 9, 2021 9:00am
Location: Off Campus Location
Organized By: Biomedical Engineering

Spinal cord stimulation (SCS) is a neuromodulation technique that applies electrical stimulation to the spinal cord to alter neural activity or processing. While SCS has historically been used as a last resort therapy for chronic pain management, novel applications and technologies have recently been developed that either increase the efficacy of treatment for chronic pain or drive neural activity to produce muscular activity/movement following a paralyzing spinal cord injury (SCI). Despite these recent innovations, there remain fundamental questions concerning the neural recruitment underlying these efficacious results. This work evaluated the neural activity and mechanisms for two novel SCS applications: closed-loop spinal cord stimulation for pain management, and ventral, high frequency spinal cord stimulation (HF-SCS) for inspiratory muscle activation following a SCI.

To evaluate neural activity, I developed computational models of SCS. Models consisted of 3 components: a finite element model (FEM) of the spinal cord to predict voltages during stimulation, biophysical neuron models, and algorithms to apply time-dependent extracellular voltages to the neuron models and simulate their response. While this cutting-edge modeling methodology could be used to predict neural activity following stimulation, it was unclear how common anatomical or technical model simplifications affected neural predictions. Therefore, the initial goal of this work was to evaluate how modeling assumptions influence neural behavior.

My initial work identified how several relevant anatomical and technical factors influence model predictions of neural activity. To evaluate these factors, I designed an FEM of a T9 thoracic spine with an implanted electrode. Then, I sequentially removed details from the model and quantified the changes in neural predictions. I identified several factors with profound (>30%) impacts on neural thresholds, including overall model impedance (for voltage-controlled stimulation), the presence of a detailed vertebral column, and dura mater conductivity. I also identified several factors that could safely be ignored in future models. This work will be invaluable as a guide for future model development.

Next, I developed a canine model to evaluate T2 ventral HF-SCS for inspiratory muscle activation. I designed and positioned two neuron models hypothesized to lead to inspiratory behavior: ventrolateral funiculus fibers (VLF) leading to diaphragm activation and inspiratory intercostal motoneurons. With this model, I predicted robust VLF and T2-T5 motoneuron recruitment within the physiologic range of stimulation. Additionally, I designed two stimulation leads that maximize inspiratory neuron recruitment. The finalized leads were evaluated via in vivo experiments, which found excellent agreement with the model. This work builds our mechanistic understanding of this novel therapy, improves its implementation, and aids in future translational efforts towards human subjects.

Finally, I developed a computational model to evaluate closed-loop stimulation for chronic pain. This work characterized the neural origins of the evoked compound action potential (ECAP), the controlling biomarker of closed-loop stimulation. I modified my modeling methodology to predict ECAPs generated during low thoracic dorsal stimulation in humans, which matched with experimental measurements. This modeling work showed that ECAP properties depend on activation of a narrow range of neuron diameters and quantified how anatomical and stimulation factors (CSF thickness, stimulation configuration, lead position, pulse width) influence ECAP morphology, timing, and neural recruitment. These results improve our mechanistic understanding of closed-loop stimulation and may lead to expanded clinical utility as well as better validation of future SCS computational models.

Date: Friday, July 9, 2021

Time: 9:00 AM EDT

Zoom: https://umich.zoom.us/j/96847307388

Chair: Dr. Scott Lempka

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Lecture / Discussion Tue, 22 Jun 2021 16:45:26 -0400 2021-07-09T09:00:00-04:00 2021-07-09T10:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo