Happening @ Michigan https://events.umich.edu/list/rss RSS Feed for Happening @ Michigan Events at the University of Michigan. BME 500: Meghan Driscoll, Ph.D. (January 30, 2020 4:00pm) https://events.umich.edu/event/70418 70418-17594468@events.umich.edu Event Begins: Thursday, January 30, 2020 4:00pm
Location: Electrical Engineering and Computer Science Building
Organized By: Biomedical Engineering

Signaling is governed not only by the expression levels of molecules, but by their localization via mechanisms as diverse as compartmentalization in organelles, phase separation, and directed transport by motor proteins. Cell morphology likely also modulates the localization of signaling molecules, and recent advances in high-resolution light-sheet microscopy, such as lattice light-sheet microscopy, now allow imaging at the spatiotemporal resolution needed to capture the many undulations and quick dynamics of the 3D cell surface. However, these microscopes generate large datasets with detailed 3D movies that are impossible to interpret without a dedicated computational pipeline. In this seminar, I will introduce u-shape3D, a computer graphics and machine-learning pipeline to probe molecular mechanisms underlying 3D cell morphogenesis. U-shape3D includes a generic morphological motif detector that automatically finds lamellipodia, filopodia, blebs and other motifs in order to test the intriguing possibility that morphogenesis itself affects intracellular signaling.

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Lecture / Discussion Thu, 23 Jan 2020 11:24:58 -0500 2020-01-30T16:00:00-05:00 2020-01-30T17:00:00-05:00 Electrical Engineering and Computer Science Building Biomedical Engineering Lecture / Discussion BME Logo
BME Student Speaker: Xiaotian Tan (February 3, 2020 12:00pm) https://events.umich.edu/event/72234 72234-17963872@events.umich.edu Event Begins: Monday, February 3, 2020 12:00pm
Location: Lurie Biomedical Engineering (formerly ATL)
Organized By: Biomedical Engineering

Biosensors are devices or systems that can be used to detect, quantify, and analyze targets with biological activities and functions. As one of the largest subsets of biosensors, biomolecular sensors are specifically developed and programmed to detect, quantify and analyze biomolecules in liquid samples. Wide-ranging applications have made immunoassays increasingly popular for biomolecular detection and quantification. Among these, enzyme-linked immunosorbent assays (ELISA) are of particular interest due to high specificity and reproducibility. To some extent, ELISA has been regarded as a “gold standard” for quantifying analytes (especially protein analytes) in both clinical diagnostics and fundamental biological research. However, traditional (96-well plate-based) ELISA still suffers from several notable drawbacks, such as long assay time (4–6 hours), lengthy procedures, and large sample/reagent consumption (∼100 μL). These inherent disadvantages still significantly limit traditional ELISA's applicability to areas such as rapid clinical diagnosis of acute diseases (e.g., viral pneumonia, acute organ rejection), and biological research that requires accurate measurements with precious or low abundance samples (e.g., tail vein serum from a mouse). Thus, a bimolecular sensing technology that has high sensitivity, short assay time, and small sample/reagent consumption is still strongly desired. In this dissertation, we introduce the development of a multifunctional and automated optofluidic biosensing platform that can resolve the aforementioned problems. In contrast to conventional plate-based ELISA, our optofluidic ELISA platform utilizes mass-producible polystyrene microfluidic channels with a high surface-to-volume ratio as the immunoassay reactors, which greatly shortens the total assay time. We also developed a low-noise signal amplification protocol and an optical signal quantification system that was optimized for the optofluidic ELISA platform. Our optofluidic ELISA platform provides several attractive features such as small sample/reagent consumption (<8 μL), short total assay time (30-45 min), high sensitivity (~1 pg/mL for most markers), and a broad dynamic range (3-4 orders of magnitude). Using these features, we successfully quantified mouse FSH (follicle stimulating hormone) concentration with a single drop of tail vein serum. We also successfully monitored bladder cancer progression in orthotopic xenografted mice with only <50 μL of mouse urine. More excitingly, we achieved highly-sensitive exosome quantification and multiplexed immuno-profiling with <40 ng/mL of total input protein (per assay). These remarkable milestones could not be achieved with conventional plate-based ELISA but were enabled by our unique optofluidic ELISA.

As an emerging member of the bimolecular sensor family, our optofluidic ELISA platform provides a high-performance and cost-effective tool for a plethora of applications, including endocrinal, cancer animal model, cellular biology, and even forensic science research. In the future, this technology platform can also be renovated for clinical applications such as personalized cancer diagnosis/prognosis and rapid point-of-care diagnostics for infectious diseases.

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Lecture / Discussion Thu, 30 Jan 2020 09:19:52 -0500 2020-02-03T12:00:00-05:00 2020-02-03T13:00:00-05:00 Lurie Biomedical Engineering (formerly ATL) Biomedical Engineering Lecture / Discussion Xiaotian Tan
BME 500: Jun Li, Ph.D. (February 6, 2020 4:00pm) https://events.umich.edu/event/70419 70419-17594471@events.umich.edu Event Begins: Thursday, February 6, 2020 4:00pm
Location: Electrical Engineering and Computer Science Building
Organized By: Biomedical Engineering

In today’s research we often talk about knowledge-extraction from Big Data, and integration across different scales: molecules, cells, tissues/organs, organisms and their communities. The pursuit of multi-scale synthesis has a long history. For the microscopic world we have largely succeeded in connecting the chemical properties of molecules with the facts of atoms and their constituents and interactions. In epidemiology, many are currently applying linear mixed models to quantify the genetic contribution of disease risks in the general population. By and large, we live with the tacit belief that basic principles, once found, will be simple and elegant, and that we can build Systems Biology from the ground level. This leads to a pointillistic research culture, as when we try to explain the heredity of complex traits by summing up the individual actions of millions of DNA variants, or when we look for the neural basis of behavior by the connectivity and firing patterns of millions of neurons.
I will use this talk to share some thoughts on the emerging appreciation that, in biomedical data science, perhaps the best one can learn is not widely generalizable Mechanisms, but different laws for different scales of organization. There may not be a good chance, and perhaps no need, to "know" a system by brute force accumulation of larger and larger data at the bottom level. Acknowledging the irreducibility of highly-level phenomena in biology and medicine can help us appreciate the distinct methods, norms, and compromises in traditional disciplines, and steer the society's investment towards balanced collection of good data on all levels. By giving up the blind celebration of sample size, we give more attention to new technologies that can measure what was previously inaccessible, and to the next-generation of information science that embraces messy, context-specific models.

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Lecture / Discussion Fri, 31 Jan 2020 15:04:28 -0500 2020-02-06T16:00:00-05:00 2020-02-06T17:00:00-05:00 Electrical Engineering and Computer Science Building Biomedical Engineering Lecture / Discussion BME Logo
Startup Career Fair (February 7, 2020 12:00pm) https://events.umich.edu/event/72206 72206-17957291@events.umich.edu Event Begins: Friday, February 7, 2020 12:00pm
Location: Duderstadt Center
Organized By: MPowered Entrepreneurship

Startup Career Fair provides students with the opportunity to pursue their passion and get paid for it. From Productiv in San Francisco to Choco from Berlin, world-renowned startups with mission-driven teams are waiting to hire you.

We invite you to join us on February 7 from 12-4pm at the Duderstadt Center on North Campus. Register by February 4th and you'll be entered into a lottery for an invitation to our exclusive networking breakfast with recruiters. Can’t wait to see you #Launch.

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Careers / Jobs Wed, 29 Jan 2020 13:06:39 -0500 2020-02-07T12:00:00-05:00 2020-02-07T16:00:00-05:00 Duderstadt Center MPowered Entrepreneurship Careers / Jobs #Launch
BME Ph.D Defense: Xiaotian Tan (February 12, 2020 11:00am) https://events.umich.edu/event/72235 72235-17963874@events.umich.edu Event Begins: Wednesday, February 12, 2020 11:00am
Location: Cooley Building
Organized By: Biomedical Engineering

Biosensors are devices or systems that can be used to detect, quantify, and analyze targets with biological activities and functions. As one of the largest subsets of biosensors, biomolecular sensors are specifically developed and programmed to detect, quantify and analyze biomolecules in liquid samples.

Wide-ranging applications have made immunoassays increasingly popular for biomolecular detection and quantification. Among these, enzyme-linked immunosorbent assays (ELISA) are of particular interest due to high specificity and reproducibility. To some extent, ELISA has been regarded as a “gold standard” for quantifying analytes (especially protein analytes) in both clinical diagnostics and fundamental biological research. However, traditional (96-well plate-based) ELISA still suffers from several notable drawbacks, such as long assay time (4–6 hours), lengthy procedures, and large sample/reagent consumption (∼100 μL). These inherent disadvantages still significantly limit traditional ELISA's applicability to areas such as rapid clinical diagnosis of acute diseases (e.g., viral pneumonia, acute organ rejection), and biological research that requires accurate measurements with precious or low abundance samples (e.g., tail vein serum from a mouse). Thus, a bimolecular sensing technology that has high sensitivity, short assay time, and small sample/reagent consumption is still strongly desired.

In this dissertation, we introduce the development of a multifunctional and automated optofluidic biosensing platform that can resolve the aforementioned problems. In contrast to conventional plate-based ELISA, our optofluidic ELISA platform utilizes mass-producible polystyrene microfluidic channels with a high surface-to-volume ratio as the immunoassay reactors, which greatly shortens the total assay time. We also developed a low-noise signal amplification protocol and an optical signal quantification system that was optimized for the optofluidic ELISA platform.

Our optofluidic ELISA platform provides several attractive features such as small sample/reagent consumption (<8 µL), short total assay time (30-45 min), high sensitivity (~1 pg/mL for most markers), and a broad dynamic range (3-4 orders of magnitude). Using these features, we successfully quantified mouse FSH (follicle stimulating hormone) concentration with a single drop of tail vein serum. We also successfully monitored bladder cancer progression in orthotopic xenografted mice with only <50 µL of mouse urine. More excitingly, we achieved highly-sensitive exosome quantification and multiplexed immuno-profiling with <40 ng/mL of total input protein (per assay). These remarkable milestones could not be achieved with conventional plate-based ELISA but were enabled by our unique optofluidic ELISA.

As an emerging member of the bimolecular sensor family, our optofluidic ELISA platform provides a high-performance and cost-effective tool for a plethora of applications, including endocrinal, cancer animal model, cellular biology, and even forensic science research. In the future, this technology platform can also be renovated for clinical applications such as personalized cancer diagnosis/prognosis and rapid point-of-care diagnostics for infectious diseases.

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Lecture / Discussion Thu, 30 Jan 2020 09:28:04 -0500 2020-02-12T11:00:00-05:00 2020-02-12T12:00:00-05:00 Cooley Building Biomedical Engineering Lecture / Discussion Xiaotian Tan
BME 500: Leyuan Ma, Ph.D. (February 13, 2020 4:00pm) https://events.umich.edu/event/70420 70420-17594472@events.umich.edu Event Begins: Thursday, February 13, 2020 4:00pm
Location: Electrical Engineering and Computer Science Building
Organized By: Biomedical Engineering

Chimeric antigen receptor (CAR) T-cell therapy has shown dramatic clinical responses in hematologic malignancies, with a high proportion of durable complete remissions elicited in leukemia and lymphomas. However, achieving the full promise of CAR T-cell therapy, especially in solid tumors, will require further advances in this form of cellular therapy. A key challenge is maintaining a sufficient pool of functional CAR T cells in vivo. We recently developed a strategy to target vaccines to lymph nodes, by linking peptide antigens to albumin-binding phospholipid-polymers. Constitutive trafficking of albumin from blood to lymph makes it ideal chaperone to concentrate these “amphiphile-vaccine” molecules in lymph nodes that would otherwise be rapidly dispersed in the bloodstream following parenteral injection. These lipid-polymer conjugates also exhibit the property that they insert in cell membranes on arrival in lymph nodes. Here, we generated amphiphile CAR T ligand (amph-ligand) vaccine by exploiting these dual lymph node targeting and membrane-decorating properties to repeatedly expand and rejuvenate CAR T cells through the chimeric receptor in native lymph node microenvironment. We evaluated this approach in the presence of a complete host immune system. Amph-ligand vaccine boosting triggered massive CAR T expansion, increased donor cell polyfunctionality, and enhanced anti-tumor efficacy in multiple immunocompetent tumor models. We demonstrate two approaches to generalize this strategy to any CAR, enabling this simple HLA-independent vaccination approach to enhance CAR T functionality to be applied to existing CAR T cell designs. Taken together, our amph-ligand vaccine provides a simple engineering solution to augment CAR T-cell therapy.

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Lecture / Discussion Fri, 07 Feb 2020 13:11:56 -0500 2020-02-13T16:00:00-05:00 2020-02-13T17:00:00-05:00 Electrical Engineering and Computer Science Building Biomedical Engineering Lecture / Discussion BME Logo
BME Ph.D. Defense: Lauren L. Zimmerman (February 20, 2020 10:00am) https://events.umich.edu/event/72566 72566-18018159@events.umich.edu Event Begins: Thursday, February 20, 2020 10:00am
Location: Lurie Robert H. Engin. Ctr
Organized By: Biomedical Engineering

Department of Biomedical Engineering Final Oral Examination

Lauren L. Zimmerman

Investigating Neuromodulation as a Treatment for Female Sexual Dysfunction

Female sexual dysfunction (FSD) affects millions of women worldwide. FSD has a significant impact on quality of life and interpersonal relationships. The prevalence of at least one form of sexual dysfunction is 40-45% of adult women with 12% of women experiencing sexually related personal distress, yet there is no clear treatment option for a wide range of FSD deficits with high efficacy and low side effects.

Neuromodulation techniques using electrical stimulation of peripheral nerves have the potential to treat some forms of FSD. In clinical trials of sacral neuromodulation (SNM) and percutaneous tibial nerve stimulation (PTNS) for bladder dysfunction, women have reported that their sexual dysfunction symptoms improved as well. Even though this effect has been observed clinically, very little research has been done to examine the mechanisms or the optimal method of treatment specifically for women with FSD. This thesis aims to bridge that gap by investigating neuromodulation as a treatment for FSD through both preclinical and clinical studies.

The first aim of this thesis is to investigate a possible mechanism of the improvement to sexual functioning in response to tibial nerve stimulation by evaluating vaginal blood flow responses in rats. In 16 ketamine-anesthetized female rats, the tibial nerve was stimulated for 30 minutes while vaginal blood perfusion was recorded with laser Doppler flowmetry. A novel signal analysis and quantification metric was developed for this analysis. I found that tibial nerve stimulation could drive prolonged increases in vaginal blood perfusion, typically after 20-30 minutes of stimulation. This result suggests that clinical neuromodulation may be improving FSD symptoms by increasing genital blood flow.

One question yet to be investigated by neuromodulation studies is whether tibial nerve stimulation could be an on-demand treatment for FSD, such as Viagra is for men, or is more appropriate as a long-term treatment with improvements over time, such as PTNS for bladder dysfunction. In this thesis I address this question by evaluating the sexual motivation and receptivity of female rats both immediately after a single stimulation session as well as after long-term, repeated stimulation sessions. I found that tibial nerve stimulation led to modest increases in sexual motivation in the short term, and larger increases in sexual receptivity in the long-term.

Lastly, this thesis evaluates a pilot clinical study of transcutaneous stimulation of the dorsal genital and posterior tibial nerves in nine women with FSD. The women received stimulation once a week for 12 weeks and their sexual functioning was measured using the Female Sexual Function Index (FSFI) at baseline, after 6 weeks of stimulation, after 12 weeks of stimulation, and at 18 weeks (6 weeks after the last stimulation session). The average total FSFI score across all subjects significantly increased from baseline to each of the time points in the study. Significant FSFI increases were seen in the sub-domains of lubrication, arousal, and orgasm, each of which is related to genital arousal.

This thesis provides evidence that peripheral neuromodulation can be an effective treatment for FSD. The stimulation is likely driving increases in genital blood flow, with greater effects observed when stimulation is repeatedly applied over time. This treatment has the potential to help millions of women worldwide.

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Lecture / Discussion Wed, 05 Feb 2020 15:00:05 -0500 2020-02-20T10:00:00-05:00 2020-02-20T11:00:00-05:00 Lurie Robert H. Engin. Ctr Biomedical Engineering Lecture / Discussion BME Logo
Microfluidics Seminar: Dr. Xufeng Xue (February 20, 2020 12:00pm) https://events.umich.edu/event/73026 73026-18129602@events.umich.edu Event Begins: Thursday, February 20, 2020 12:00pm
Location: Pierpont Commons
Organized By: Biomedical Engineering

Neurulation is a key embryonic developmental process that gives rise to neural tube (NT), the precursor structure that eventually develops into the central nervous system (CNS). Understanding the molecular mechanisms and morphogenetic events underlying human neurulation is important for the prevention and treatment of neural tube defects (NTDs) and neurodevelopmental disorders. However, animal models are limited in revealing many fundamental aspects of neurulation that are unique to human CNS development. Furthermore, the technical difficulty and ethical constraint in accessing neurulation-stage human embryos have significantly limited experimental investigations of early human CNS development.
I leveraged the developmental potential and self-organizing property of human pluripotent stem cells (hPSCs) in conjunction with 2D and 3D bioengineering tools to achieve the development of spatially patterned multicellular tissues that mimic certain aspects of human neurulation, including neuroectoderm patterning and dorsal-ventral (DV) patterning of NT.
In the first section, I report a micropatterned hPSC-based neuroectoderm model, wherein pre-patterned geometrical confinement induces emergent patterning of neuroepithelial (NE) and neural plate border (NPB) cells, mimicking neuroectoderm patterning during early neurulation. My data support the hypothesis that in this hPS cell-based neuroectoderm patterning model, two tissue-scale morphogenetic signals, cell shape and cytoskeletal contractile force, instruct NE / NPB patterning via BMP-SMAD signaling. This work provides evidence of tissue mechanics-guided neuroectoderm patterning and establishes a tractable model to study signaling crosstalk involving both biophysical and biochemical determinants in neuroectoderm patterning.
In the second section, I report a human NT development model, in which NT-like tissues, termed NE cysts, are generated in a bioengineered neurogenic environment through self-organization of hPSCs. DV patterning of NE cysts is achieved using retinoic acid and/or Sonic Hedgehog, featuring sequential emergence of the ventral floor plate, p3 and pMN domains in discrete, adjacent regions and dorsal territory that is progressively restricted to the opposite dorsal pole.

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Lecture / Discussion Tue, 18 Feb 2020 08:58:46 -0500 2020-02-20T12:00:00-05:00 2020-02-20T13:00:00-05:00 Pierpont Commons Biomedical Engineering Lecture / Discussion BME Logo
BME 500: Ruixuan Gao (February 20, 2020 4:00pm) https://events.umich.edu/event/70421 70421-17594473@events.umich.edu Event Begins: Thursday, February 20, 2020 4:00pm
Location: Electrical Engineering and Computer Science Building
Organized By: Biomedical Engineering

Investigation of the molecular basis of a complex biological system, such as the brain, can lead to fundamental understanding of its composition and function, and to a new strategy to repair it. Such investigation, however, requires a tool that can capture biological structures and their molecular constituents across multiple orders of magnitude—from nanometers to centimeters—in length. Electron microscopy offers nanoscopic resolution but lacks molecular information to differentiate endogenous biomolecules as well as imaging speed to cover millimeter-scale specimens. Light microscopy provides molecular contrast but is limited by optical diffraction and the tradeoff between imaging speed and photobleaching.

In this talk, I will first introduce an optical imaging pipeline named expansion lattice light-sheet microscopy (ExLLSM) and its application to multiplexed, volumetric imaging of molecular constituents in cells and intact tissues. Using ExLLSM, our study has revealed molecular-specific structures of organelles, synapses, myelin sheaths, and neurites in rodent and insect brains at ∼60 by 60 by 90 nm effective resolution across dimensions that span millimeters. Next, I will present two recently developed methods that further extend the resolution and throughput of ExLLSM: (1) a non-radical hydrogel chemistry that forms a homogenous polymer network and physically separates biomolecules or fluorescent labels up to 40-fold linearly, and (2) a multi-modal optical microscopy that enables rapid, high-resolution imaging of both expanded and live tissues. Lastly, I will discuss the significance of these imaging methods in the context of microanatomy and functional omics.

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Lecture / Discussion Thu, 13 Feb 2020 10:34:18 -0500 2020-02-20T16:00:00-05:00 2020-02-20T17:00:00-05:00 Electrical Engineering and Computer Science Building Biomedical Engineering Lecture / Discussion BME Logo
BME 500: Kelly Stevens (February 27, 2020 4:00pm) https://events.umich.edu/event/70067 70067-17505693@events.umich.edu Event Begins: Thursday, February 27, 2020 4:00pm
Location: Electrical Engineering and Computer Science Building
Organized By: Biomedical Engineering

The notion of building artificial human organs has moved from a far-fetched concept to the forefront of regenerative medicine research. While progress is being made, most tissues created to date are simply not large enough to support clinically meaningful functions, and their structural features remain an magnitude coarser in resolution than native tissues. Few organs better represent this challenge than the liver – the largest visceral organ in the human body, in which hepatocytes are aligned in single cell-width structures entangled with vascular and biliary networks. To address this challenge, we are working to develop a portfolio of tools that integrate 3D printing, synthetic biology, and the innate capacity of cells to self-assemble. We are applying these tools to decode the signals that drive tissue assembly during development, and using this information to build scaled artificial tissues that replicate the features of native tissues.

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Workshop / Seminar Thu, 20 Feb 2020 11:04:16 -0500 2020-02-27T16:00:00-05:00 2020-02-27T17:00:00-05:00 Electrical Engineering and Computer Science Building Biomedical Engineering Workshop / Seminar BME Event
BME 500: Ruobo Zhou (March 5, 2020 4:00pm) https://events.umich.edu/event/73399 73399-18214945@events.umich.edu Event Begins: Thursday, March 5, 2020 4:00pm
Location: Industrial and Operations Engineering Building
Organized By: Biomedical Engineering

Biomolecular interactions are at the root of all biological processes and define the molecular mechanisms of how these processes are accomplished in both physiological and pathological conditions. Recent advances in single molecule detection and super-resolution fluorescence microcopy have uncovered previously unknown properties of biomolecular interactions, including multivalency, transiency, and heterogeneity, and revealed the organizational principles governing the compartmentalization of functional biomolecular interactions in cells and how such compartmentalization and organizations become dysregulated in diseases. In this talk, I will first discuss my postdoctoral work, where I used mass-spectrometry-based analysis and super-resolution imaging to dissect the protein-protein interactions at the plasma membrane of neurons, and discovered that a newly identified membrane-associated periodic skeleton (MPS) structure can function as a signaling platform that coordinates the interactions of signaling proteins at the plasma membrane of neurons. In response to extracellular stimuli, G-protein coupled receptors, cell-adhesion molecules, receptor tyrosine kinases can be recruited to the MPS to form signaling complexes at the plasma membrane, and such recruitment is required for downstream intracellular signaling. This work not only reveals an important, previously unknown function of the newly discovered MPS structure, but also provides novel mechanistic insights into signal transduction in neurons. I will then discuss my graduate work, where I developed a hybrid single molecule technique combining single molecule FRET and optical tweezers, and applied this technique to probe the sub-molecular dynamics of protein-DNA interactions in various biological systems involved in DNA replication, repair and recombination.

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Lecture / Discussion Fri, 28 Feb 2020 11:07:38 -0500 2020-03-05T16:00:00-05:00 2020-03-05T17:00:00-05:00 Industrial and Operations Engineering Building Biomedical Engineering Lecture / Discussion BME Logo
BME 500: Rebecca Wachs (March 12, 2020 4:00pm) https://events.umich.edu/event/70068 70068-17505695@events.umich.edu Event Begins: Thursday, March 12, 2020 4:00pm
Location: Electrical Engineering and Computer Science Building
Organized By: Biomedical Engineering

The majority of the population will experience low back pain in their lifetime. Degeneration of the intervertebral disc is highly correlated with low back pain, however, not all disc degeneration is painful. One of the most common forms of low back pain is disc-associated low back pain in which pain originates from intervertebral disc. In disc-associated low back pain, nerve fibers penetrate the previously aneural disc, where they are then thought to be stimulated by the harsh catabolic environment. Repetitive stimulation of these nerve fibers can cause sensitization and chronic pain. The overarching goal of our work is to engineer biomaterials that target these two key areas of disc-associated low back pain: nerve growth and stimulation. Current clinical treatments for chronic low back pain have limited efficacy or are highly invasive. The majority of research to date focuses on regenerating a young healthy disc. We believe our approach to target nerve growth and stimulation independent of disc regeneration has the potential shift the paradigm in the treatment of low back pain.

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Workshop / Seminar Tue, 10 Mar 2020 11:43:59 -0400 2020-03-12T16:00:00-04:00 2020-03-12T17:00:00-04:00 Electrical Engineering and Computer Science Building Biomedical Engineering Workshop / Seminar BME Event
Annual Symposium in Biophysics (March 13, 2020 8:00am) https://events.umich.edu/event/69839 69839-17472589@events.umich.edu Event Begins: Friday, March 13, 2020 8:00am
Location: Michigan Union
Organized By: LSA Biophysics

TBD

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Conference / Symposium Mon, 02 Dec 2019 08:43:25 -0500 2020-03-13T08:00:00-04:00 2020-03-13T17:00:00-04:00 Michigan Union LSA Biophysics Conference / Symposium Michigan Union
CANCELED: Mechanisms Linking Cell Mechanics and Metabolism (March 13, 2020 12:00pm) https://events.umich.edu/event/72757 72757-18070590@events.umich.edu Event Begins: Friday, March 13, 2020 12:00pm
Location: Biological Sciences Building
Organized By: Department of Molecular, Cellular, and Developmental Biology

Host: Ann Miller

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Workshop / Seminar Tue, 10 Mar 2020 11:32:19 -0400 2020-03-13T12:00:00-04:00 2020-03-13T13:00:00-04:00 Biological Sciences Building Department of Molecular, Cellular, and Developmental Biology Workshop / Seminar microscope drawing, MCDB initials in yellow on blue background
CANCELED: Organization of cellular fat store . . . (March 17, 2020 12:00pm) https://events.umich.edu/event/72758 72758-18070591@events.umich.edu Event Begins: Tuesday, March 17, 2020 12:00pm
Location: Biological Sciences Building
Organized By: Department of Molecular, Cellular, and Developmental Biology

This seminar has been cancelled.

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Workshop / Seminar Tue, 10 Mar 2020 10:50:42 -0400 2020-03-17T12:00:00-04:00 2020-03-17T13:00:00-04:00 Biological Sciences Building Department of Molecular, Cellular, and Developmental Biology Workshop / Seminar MCDB initials and yellow microscope drawing on a blue square
Canceled: Shaping the cell from the outside in (March 20, 2020 12:00pm) https://events.umich.edu/event/72760 72760-18070592@events.umich.edu Event Begins: Friday, March 20, 2020 12:00pm
Location: Biological Sciences Building
Organized By: Department of Molecular, Cellular, and Developmental Biology

Host: Anthony Vecchiarelli

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Workshop / Seminar Tue, 10 Mar 2020 14:55:11 -0400 2020-03-20T12:00:00-04:00 2020-03-20T13:00:00-04:00 Biological Sciences Building Department of Molecular, Cellular, and Developmental Biology Workshop / Seminar MCDB initials & microscope drawing in yellow on a blue square
Zhen Xu, PhD: Histotripsy Webinar (March 25, 2020 10:00am) https://events.umich.edu/event/73931 73931-18426654@events.umich.edu Event Begins: Wednesday, March 25, 2020 10:00am
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This will be held online. Click the link below to register.

https://fusfoundation.zoom.us/webinar/register/WN_Hj_R2DMOT8SlOAp0WRLV3A

Oftentimes when we think of focused ultrasound, we imagine using it to heat and kill tissue. Unlike thermal ablation, histotripsy uses focused ultrasound to mechanically disrupt the target tissue without heating. Histotripsy turns the tissue into liquid-appearing acellular debris – which is absorbed by the body over one to two months – resulting in effective tissue removal.

Histotripsy has been shown to stimulate a powerful immune response in cancer treatment studies. In the treatment of neurological diseases, transcranial histotripsy can produce well-confined focal treatment in a wide range of locations and volumes in the brain, offering the potential to increase the treatment envelope while decreasing treatment time.

Please register to join us at 10:00 AM Eastern on Wednesday, March 25, when Zhen Xu, PhD, will discuss the basic mechanism, instrumentation, bioeffects, and applications of histotripsy. She will also cover the latest preclinical and clinical trial results of developing histotripsy for the treatment of cancer and neurological diseases.

About the Speaker

Zhen Xu, PhD, is a tenured Associate Professor in the Department of Biomedical Engineering at the University of Michigan and a primary inventor and pioneer in histotripsy.

She has received many notable awards, including:
IEEE Ultrasonics, Ferroelectrics, and Frequency Control Society Outstanding Paper Award (2006)
American Heart Association Outstanding Research in Pediatric Cardiology (2010)
National Institutes of Health (NIH) New Investigator Award at the First National Institute of Biomedical Imaging and Bioengineering (NIBIB) Edward C. Nagy New Investigator Symposium (2011)
The Federic Lizzi Early Career Award from The International Society of Therapeutic Ultrasound (ISTU) (2015)
Fellow of the American Institute of Medical and Biological Engineering (2019)
Dr. Xu is currently an associate editor for three notable journals: IEEE Transactions on Ultrasound, Ferroelectrics, and Frequency Control (UFFC); Frontiers in Bioengineering; and BME Frontiers. She is an elected board member of ISTU, a charter member of the US NIH study section, and a principal investigator of grants funded by the Focused Ultrasound Foundation, NIH, American Cancer Association, Office of Naval Research, The Hartwell Foundation, and The Coulter Foundation.

She received her PhD from the University of Michigan in 2005.

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Livestream / Virtual Mon, 23 Mar 2020 14:42:17 -0400 2020-03-25T10:00:00-04:00 2020-03-25T11:00:00-04:00 Off Campus Location Biomedical Engineering Livestream / Virtual BME Logo
Ph.D. Defense: Tyler Gerhardson (March 26, 2020 10:00am) https://events.umich.edu/event/73025 73025-18129601@events.umich.edu Event Begins: Thursday, March 26, 2020 10:00am
Location: Lurie Robert H. Engin. Ctr
Organized By: Biomedical Engineering

NOTICE: Will be held via BlueJeans.

Link: https://umich.bluejeans.com/924142541

Brain pathologies including stroke and cancer are a major cause of death and disability. Intracerebral hemorrhage (ICH) accounts for roughly 12% of all strokes in the US with approximately 200,000 new cases per year. ICH is characterized by the rupture of vessels resulting in bleeding and clotting inside the brain. The presence of the clot causes immediate damage to surrounding brain tissue via mass effect with delayed toxic effects developing in the days following the hemorrhage. This leads ICH patients to high mortality with a 40% chance of death within 30 days of diagnosis and motivates the need to quickly evacuate the clot from the brain. Craniotomy surgery and other minimally invasive methods using thrombolytic drugs are common procedures to remove the clot but are limited by factors such as morbidity and high susceptibility to rebleeding, which ultimately result in poor clinical outcomes.

Histotripsy is a non-thermal ultrasound ablation technique that uses short duration, high amplitude rarefactional pulses (>26 MPa) delivered via an extracorporeal transducer to generate targeted cavitation using the intrinsic gas nuclei existing in the target tissue. The rapid and energetic bubble expansion and collapse of cavitation create high stress and strain in tissue at the focus that fractionate it into an acellular homogenate. This dissertation presents the role of histotripsy as a novel ultrasound technology with potential to address the need for an effective transcranial therapy for ICH and other brain pathologies.

The first part of this work investigates the effects of ultrasound frequency and focal spacing on transcranial clot liquefaction using histotripsy. Histotripsy pulses were delivered using two 256-element hemispherical transducers of different frequency (250 and 500 kHz) with 30-cm aperture diameters. Liquefied clot was drained via catheter and syringe in the range of 6-59 mL in 0.9-42.4 min. The fastest rate was 16.6 mL/min. The best parameter combination was λ spacing at 500 kHz, which produced large liquefaction through 3 skullcaps (~30 mL) with fast rates (~2 mL/min). The temperature-rise through the 3 skullcaps remained below 4°C.

The second part addresses initial safety concerns for histotripsy ICH treatment through investigation in a porcine ICH model. 1.75-mL clots were formed in the frontal lobe of the brain. The centers of the clots were liquefied with histotripsy 48 h after formation, and the content was either evacuated or left within the brain. A control group was left untreated. Histotripsy was able to liquefy the core of clots without direct damage to the perihematomal brain tissue. An average volume of 0.9 ± 0.5 mL (~50%) was drained after histotripsy treatment. All groups showed mild ischemia and gliosis in the perihematomal region; however, there were no deaths or signs of neurological dysfunction in any groups.

The third part presents the development of a novel catheter hydrophone method for transcranial phase aberration correction and drainage of the clot liquefied with histotripsy. A prototype hydrophone was fabricated to fit within a ventriculostomy catheter. Improvements in focal pressure of up to 60% were achieved at the geometric focus and 27%-62% across a range of electronic steering locations. The sagittal and axial -6-dB beam widths decreased from 4.6 to 2.2 mm in the sagittal direction and 8 to 4.4 mm in the axial direction, compared to 1.5 and 3 mm in the absence of aberration. The cores of clots liquefied with histotripsy were readily drained via the catheter.

The fourth part focuses on the development of a preclinical system for translation to human cadaver ICH models. A 360-element, 700 kHz hemispherical array with a 30 cm aperture was designed and integrated with an optical tracker surgical navigation system. Calibrated simulations of the transducer suggest a therapeutic range between 48 – 105 mL through the human skull with the ability to apply therapy pulses at pulse-repetition-frequencies up to 200 Hz. The navigation system allows real-time targeting and placement of the catheter hydrophone via a pre-operative CT or MRI.

The fifth and final part of this work extends transcranial histotripsy therapy beyond ICH to the treatment of glioblastoma. This section presents results from an initial investigation into cancer immunomodulation using histotripsy in a mouse glioblastoma model. The results suggest histotripsy has some immunomodulatory capacity as evidenced by a 2-fold reduction in myeloid derived suppressor cells and large increases in interferon-γ concentrations (3500 pg/mL) within the brain tumors of mice treated with histotripsy.

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Lecture / Discussion Mon, 16 Mar 2020 13:26:52 -0400 2020-03-26T10:00:00-04:00 2020-03-26T11:00:00-04:00 Lurie Robert H. Engin. Ctr Biomedical Engineering Lecture / Discussion BME Logo
CANCELED Coatopathies: Genetic Disorders of Protein Coat (March 27, 2020 12:00pm) https://events.umich.edu/event/72762 72762-18070593@events.umich.edu Event Begins: Friday, March 27, 2020 12:00pm
Location: Biological Sciences Building
Organized By: Department of Molecular, Cellular, and Developmental Biology

Host: Ming Li

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Workshop / Seminar Tue, 10 Mar 2020 10:49:33 -0400 2020-03-27T12:00:00-04:00 2020-03-27T13:00:00-04:00 Biological Sciences Building Department of Molecular, Cellular, and Developmental Biology Workshop / Seminar MCDB initials & microscope drawing in yellow on a blue square
Bioethics Discussion: Responsibility (April 7, 2020 7:00pm) https://events.umich.edu/event/52730 52730-12974164@events.umich.edu Event Begins: Tuesday, April 7, 2020 7:00pm
Location: Off Campus Location
Organized By: The Bioethics Discussion Group

A discussion on what we owe to ourselves and others.

NOTICE: Online hosting procedure https://bluejeans.com/7569798571.

Readings to consider:
1. Social Responsibilities of Bioethics
2. The Concept of Responsibility: Three Stages in Its Evolution within Bioethics
3. Bioethics for Whom?
4. Towards an Ethics of Blame

For more information and/or to receive a copy of the readings contact Barry Belmont at belmont@umich.edu or visit http://belmont.bme.umich.edu/bioethics-discussion-group/discussions/044-responsibility/.

Please read the blog responsibly: https://belmont.bme.umich.edu/incidental-art/

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Lecture / Discussion Thu, 02 Apr 2020 09:12:34 -0400 2020-04-07T19:00:00-04:00 2020-04-07T20:30:00-04:00 Off Campus Location The Bioethics Discussion Group Lecture / Discussion Responsibility
Master's Thesis Defense: Mingyang Wang (April 10, 2020 10:30am) https://events.umich.edu/event/73990 73990-18460430@events.umich.edu Event Begins: Friday, April 10, 2020 10:30am
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This event will be held via Blue Jeans. It will be linked before.

BlueJeans: https://bluejeans.com/315155702

Objectives
We have developed a novel anti-vascular technique, termed photo-mediated ultrasound therapy (PUT), which utilizes nanosecond duration laser pulses synchronized with ultrasound bursts to remove microvasculature through cavitation. The objective of the current study is to explore the potential of PUT in removing cutaneous microvessels.

Methods
The auricular blood vessels of two New Zealand white rabbits were treated by PUT with a peak negative ultrasound pressure of 0.45 MPa at 0.5 MHz, and a laser fluence of 0.056 J/cm2 at 1064 nm for 10 minutes. Blood perfusion in the treated area was measured by a commercial laser speckle imaging (LSI) system before and immediately after treatment, as well as at one hour, three days, two weeks, and four weeks post treatment. Perfusion rates of 38 individual vessels from 4 rabbit ears were tracked during this time period for longitudinal assessment.

Results
The measured perfusion rates of the vessels in the treated areas, as quantified by the relative change in perfusion rate (RCPR), showed a statistically significant decrease for all time points post treatment (p<0.001). The mean decrease in perfusion is 50.79% immediately after treatment and is 32.14% at four weeks post treatment. Immediately after treatment, the perfusion rate decreased rapidly. Following this, there was a partial recovery in perfusion rate up to 3 days post treatment, then followed by a plateau in the perfusion from 3 days to 4 weeks.

Conclusions
The study demonstrated that a single PUT treatment could significantly reduce blood perfusion by 32.14% in the skin for up to 4 weeks. With unique advantages such as low laser fluence as compared with photothermolysis and agent-free treatment as compared with PDT, PUT holds potential to be developed into a new tool for the treatment of microvessels in the skin.

Keywords: laser; ultrasound; anti-vascular treatment; skin microvessels; photo-mediated ultrasound therapy

Chair: Dr. Xueding Wang

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Lecture / Discussion Fri, 27 Mar 2020 13:53:59 -0400 2020-04-10T10:30:00-04:00 2020-04-10T11:30:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Joel Tan (April 14, 2020 2:00pm) https://events.umich.edu/event/73953 73953-18443421@events.umich.edu Event Begins: Tuesday, April 14, 2020 2:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

NOTICE: This PhD defense will be taking place via Blue Jeans. Link below.

Blue Jeans: https://bluejeans.com/304616213
Chair: Dr. Xueding Wang

Photoacoustic (PA) imaging is an emerging biomedical imaging modality that combines optical and ultrasound imaging technologies. PA imaging relies on the absorption of electromagnetic energy (usually in the form of visible or near-infrared light) leading to the generation of acoustic waves by thermoelastic expansion, which can be detected with an ultrasound detector. PA imaging can be used to detect endogenous chromophores such as deoxyhemoglobin and oxyhemoglobin, or can be used together with external nanosensors for added functionality. The former is used to measure things like blood oxygenation, while the latter opens up many possibilities for PA imaging, limited only to the availability of optical nanosensors. In this dissertation, I employ the use of PA nanosensors for contrast enhancement and molecular imaging in in vivo small animal cancer models.

In the first section, I introduce a novel PA background reduction technique called the transient triplet differential (TTD) method. The TTD method exploits the fact that phosphorescent dyes possess a triplet state with a unique red-shifted absorption wavelength, distinct from its ordinary singlet state absorption profile. By pumping these dyes into the triplet state and comparing the signal to the unpumped dyes, a differential signal can be obtained which solely originates from these dyes. Since intrinsic chromophores of biological tissue are not able to undergo intersystem crossing and enter the triplet state, the TTD method can facilitate “true” background free molecular imaging by excluding the signals from every other chromophore outside the phosphorescent dye. Here, I demonstrate up to an order of magnitude better sensitivity of the TTD method compared to other existing contrast enhancement techniques in both in vitro experiments and in vivo cancer models.

In the second section, I explore the use of a nanoparticle formulation of a repurposed FDA-approved drug called clofazimine for diagnosis of prostate cancer. Clofazimine nanoparticles have a high optical absorbance at 495 nm and has been known to specifically accumulate in macrophages as they form stable crystal-like inclusions once they are uptaken by macrophages. Due to the presence of tumor associated macrophages, it is expected that clofazimine would accumulate in much higher quantities in the cancerous prostate compared to normal prostates. Here, I show that there was indeed a significantly higher accumulation of clofazimine nanoparticles in cancerous prostates compared to normal prostates in a transgenic mouse model, which was detectable both using histology and ex vivo PA imaging.

In the third and final section, I explore the use of a potassium (K+) nanosensor together with PA imaging in measuring the in vivo K+ distribution in the tumor microenvironment (TME). K+ is the most abundant ion in the body and has recently been shown to be at a significantly higher concentration in the tumor. The reported 5-10 fold elevation (25-50 mM compared to 5 mM) in the tumor has been shown to inhibit immune cell efficacy, and thus immunotherapy. Despite the abundance and importance of K+ in the body, few ways exist to measure it in vivo. In this study, a solvatochromic dye K+ nanoparticle (SDKNP) was used together with PA imaging to quantitatively measure the in vivo distribution of K+ in the TME. Significantly elevated K+ levels were found in the TME, with an average concentration of approximately 29 mM, matching the values found by the previous study. The results were then verified using mass spectrometry.

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Lecture / Discussion Wed, 25 Mar 2020 13:19:15 -0400 2020-04-14T14:00:00-04:00 2020-04-14T15:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
Master's Defense: Jonathan Primeaux (April 21, 2020 2:30pm) https://events.umich.edu/event/74331 74331-18633862@events.umich.edu Event Begins: Tuesday, April 21, 2020 2:30pm
Location: Off Campus Location
Organized By: Biomedical Engineering

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

Zoom Link: https://umich.zoom.us/j/7013698675

Children with hypoplastic left heart syndrome (HLHS) must undergo multiple surgical stages to reconstruct the anatomy to a sustainable single ventricle system. Stage I palliation, or the Norwood procedure, enables circulation to both pulmonary and systemic vasculature. The aorta is reconstructed and attached to the right ventricle and a fraction of systemic flow is redirected to the pulmonary arteries (PAs) through a systemic-to-pulmonary artery shunt. Despite abundant hemodynamic data available 4-5 months after palliation, data is very scarce immediately following stage I. This data is critical in determining post-operative success. In this work, we combined population data and computational fluid dynamics (CFD) to characterize hemodynamics immediately following stage I (post-stage I) and prior to stage II palliation (pre-stage II). A patient-specific model was constructed as a baseline geometry, which was then scaled to reflect population-based morphological data at both time-points. Population-based hemodynamic data was also used to calibrate each model to reproduce blood flow representative of HLHS patients.

The post-stage I simulation produced a mean PA pressure of 22 mmHg and high-frequency oscillations within the flow field indicating highly disturbed hemodynamics. Despite mean PA pressure dropping to 14 mmHg, the pre-stage II model also produced high-frequency flow components and PA wall shear stress increases. These suboptimal conditions result from the need to ensure adequate PA flow throughout the pre-stage II period, as the shunt becomes relatively smaller compared to the growing patient size. In the future, CFD can be used to optimize shunt design and minimize these suboptimal conditions.

Chair: Dr. Alberto Figueroa

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Lecture / Discussion Fri, 17 Apr 2020 13:05:00 -0400 2020-04-21T14:30:00-04:00 2020-04-21T15:30:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
Master's Defense: Xijia Quan (April 21, 2020 3:00pm) https://events.umich.edu/event/74183 74183-18559840@events.umich.edu Event Begins: Tuesday, April 21, 2020 3:00pm
Location:
Organized By: Biomedical Engineering

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

Blue Jeans link: https://bluejeans.com/6788336326

We propose a novel optimization algorithm for radiofrequency (RF) pulse design in magnetic resonance imaging (MRI), that regularizes the magnitude and phase of the target (desired) magnetization pattern separately. This approach may be useful across applications where the relative importance of achieving accurate magnitude or phase excitation varies; for example, saturation pulses "care" only about the magnitude excitation pattern. We apply our new design to the problem of spin "prephasing" in 3D functional MRI using blood-oxygen-level-dependent (BOLD) contrast; spin prephasing pulses can mitigate the signal loss observed near air/tissue boundaries due to the presence of local susceptibility gradients. We show that our algorithm can improve the simulation performance and recover some signal in some regions with steep susceptibility gradients. In all cases, our algorithm shows better phase correction than a conventional design based on minimizing the complex difference between the target and realized patterns. The algorithm is open-source and the computation time is feasible for online applications. In addition, we evaluate the impact of the choice of (initial) excitation k-space trajectories, both in terms of trajectory type (SPINS vs extended KT points) and overall pulse duration.

Chair: Dr. Jon-Fredrik Nielsen

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Lecture / Discussion Thu, 09 Apr 2020 14:11:30 -0400 2020-04-21T15:00:00-04:00 2020-04-21T16:00:00-04:00 Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: David Martel (April 22, 2020 3:00pm) https://events.umich.edu/event/74201 74201-18568320@events.umich.edu Event Begins: Wednesday, April 22, 2020 3:00pm
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.zoom.us/j/2019377962

Tinnitus is the disorder of phantom sound perception, while hyperacusis is abnormally increased loudness growth. Tinnitus and hyperacusis are both associated with hearing loss, but hearing loss does not always occur with either condition, implicating central neural activity as the basis for each disorder. Furthermore, while tinnitus and hyperacusis can co-occur, either can occur exclusively, suggesting that separate pathological neural processes underlie each disorder.

Mounting evidence suggests that pathological neural activity in the cochlear nucleus, the first central nucleus in the auditory pathway, underpins hyperacusis and tinnitus. The cochlear nucleus is comprised of a ventral and dorsal subdivision, which have separate principle output neurons with distinct targets. Previous studies have shown that dorsal cochlear nucleus fusiform cells show tinnitus-related increases in spontaneous firing with minimal alterations to sound-evoked responses. In contrast, sound-evoked activity in ventral cochlear nucleus bushy cells is enhanced following noise-overexposure, putatively underlying hyperacusis. While the fusiform-cell contribution to tinnitus has been well characterized with behavioral and electrophysiological studies, the bushy-cell contribution to tinnitus or hyperacusis has been understudied.

This dissertation examines how pathological neural activity in cochlear nucleus circuitry relates to tinnitus and hyperacusis in the following three chapters.

In the first chapter, I characterize the development of a high-throughput tinnitus behavioral model, which combines and optimizes existing paradigms. With this model, I show that animals administered salicylate, a drug that reliably induces tinnitus at high doses in both humans and animals, show behavioral evidence of tinnitus in two separate behavioral tests. Moreover, in these same animals, I show that dorsal-cochlear-nucleus fusiform cells exhibit frequency-specific increases in spontaneous firing activity, consistent with noise-induced tinnitus in animals.

In the second chapter, I show that following noise-overexposure, ventral-cochlear-nucleus bushy cells demonstrate hyperacusis-like neural firing patterns, but not tinnitus-specific increases in spontaneous activity. I contrast the bushy-cell neural activity with established fusiform-cell neural signatures of tinnitus, to highlight the bushy-cell, but not fusiform-cell contribution to hyperacusis. These analyses suggest that tinnitus and hyperacusis likely arise from distinct neural substrates.

In the third chapter, I use computational modelling of the auditory periphery and bushy-cell circuitry to examine potential mechanisms that underlie hyperacusis-like neural firing patterns demonstrated in the second chapter. I then relate enhanced bushy-cell firing patterns to alterations in the auditory brainstem response, a sound-evoked electrical potential generated primarily by bushy cells. Findings in this chapter suggest that there are multiple hyperacusis subtypes, arising from separate mechanisms, which could be diagnosed through fine-tuned alterations to the auditory brainstem response.

Chair: Dr. Susan Shore

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Lecture / Discussion Thu, 09 Apr 2020 14:17:07 -0400 2020-04-22T15:00:00-04:00 2020-04-22T16:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Richard Youngblood (April 29, 2020 2:00pm) https://events.umich.edu/event/74358 74358-18666222@events.umich.edu Event Begins: Wednesday, April 29, 2020 2:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

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

BlueJeans: https://bluejeans.com/855683101

Human pluripotent stem cells (hPSCs) differentiated into complex three-dimensional (3D) structures, referred to as ‘organoids’ due to their organ-like properties, offer ideal platforms to study human development, disease and regeneration. However, studying organ morphogenesis has been hindered by the lack of appropriate culture systems that can spatially enable cellular interactions that are needed for organ formation. Many organoid cultures rely on decellularized extracellular matrices as supportive scaffolds, which are often poorly chemically defined and allow only limited tunability and reproducibility. By contrast, engineered synthetic matrices can be tuned and optimized to mimic the embryo environment in order to enhance development and maturation of organoid cultures. Herein, this work primarily focuses on using synthetic polymer matrices to investigate how the design of biomaterials can guide key interactions guiding stem-cell decisions for the reproducible generation and control of organoid cultures.
Microporous biomaterials comprised of synthetic polymer materials were shown to guide the assembly of pancreatic progenitors into insulin-producing clusters that further developed into islet organoids. The scaffold culture facilitated cell-cell interactions enabled by the scaffold design and supported cell-mediated matrix deposition of extracellular matrix (ECM) proteins associated with the basement membrane of islet cells. Furthermore, when compared to suspension cultures, the scaffold culture showed increased insulin secretion in response to glucose stimulus indicating the development of functional β-cells. By modifying the stage that cells were seeded on scaffolds from pancreatic progenitor to pancreatic endoderm, islet organoids showed increased amounts of insulin secreted per cell. In addition, seeding scaffolds with dense clusters instead of a single suspension minimized cell manipulation during the differentiation, which was shown to be influential to the development of the islet organoids. An engineered insulin reporter further identified how mechanistic changes in vitro influenced function within individual cells by measuring insulin storage and secretion through non-invasive imaging.
hPSC-derived lung organoids (HLOs) were also evaluated for in vivo maturation on biomaterial scaffolds, where HLOs were shown improved tissue structure and cellular differentiation. Investigative studies demonstrated that scaffold pore interconnectivity and polymer degradation contributed to in vivo maturation, the size of the airway structures and the total size of the transplanted tissue. Polymer biomaterials were also developed to modulate local tissue and systemic inflammation through local delivery of human interleukin 4 (hIL-4)-expressing lentivirus. Microporous scaffold culture strategies improve organoid complexity and exert fine control over the system using engineering solutions, thus, allowing the community to build more realistic organoid tools. Taken together, the microporous scaffold culture demonstrates the feasibility to translate organoid culture to the clinic as a biomanufacturing platform.

Chair: Dr. Lonnie Shea

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Lecture / Discussion Tue, 21 Apr 2020 13:21:55 -0400 2020-04-29T14:00:00-04:00 2020-04-29T15:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
Master's Defense: Manan Parag Anjaria (April 30, 2020 1:15pm) https://events.umich.edu/event/74435 74435-18714559@events.umich.edu Event Begins: Thursday, April 30, 2020 1:15pm
Location: Off Campus Location
Organized By: Biomedical Engineering

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

Blue Jeans Link: https://bluejeans.com/126133694

Individual muscle contributions to facilitate limb motion are altered in people with transtibial amputation. Specifically, proximal muscles on the residual limb and muscles on the intact limb compensate for the lack of plantarflexor muscles on the residual limb. Powered ankle prostheses have been developed to replace the function of the ankle plantarflexor muscles. As powered prostheses can help people with amputation walk faster, and replicate local ankle joint mechanics similar to biological ankles, we expect that muscle activity would also differ when using powered prostheses compared to unpowered prosthesis. Exploring muscle synergies, or the patterns of co-activation of muscles recruited by a single neural command signal, can provide insight into the neural control strategies used to walk with different types of prostheses. The goal of this study was to determine if the use of a powered ankle prosthesis affected muscle coordination and coactivation in comparison to the use of unpowered prosthesis. Nine people with unilateral transtibial amputation and 9 age-matched, non-amputee controls walked on a treadmill while muscle activity from 16 lower limb muscles were collected. Participants with amputation performed two trials, one with an unpowered and one with a powered prosthesis, on the same day. People with transtibial amputation had higher thigh muscle co-contraction when walking with powered prostheses. They also had the same number of synergies in both prostheses as the non-amputee group, which suggests that the complexity of the motor control strategy is not affected by amputation or prosthesis type. The first three synergies in the intact limb were similar, however, the contribution of different muscles to the fourth synergy varied in people with amputation as they used more knee flexors than ankle dorsiflexors in the late swing phase. We also explored the time-varying pattern of the synergies across the gait cycle. There were some phases of the gait cycle where activation profiles for all the synergies were significantly different between the groups with and without amputation. However, there were strong correlations between muscle weightings for each synergy between the groups with and without amputation, with both prostheses. This indicates that they used a similar muscle recruitment strategy. The use of powered prosthesis reduced the compensatory activity of the proximal muscles making the intact limb synergies muscle weightings more similar to healthy individuals with prolonged or delayed activation profiles. The study could not offer any interpretations of the synergies of the residual limb due to lesser muscle activity data available. Future work should be focused including a larger set of muscles including the lumbar muscles and residual leg muscles to get a better look at the muscle synergy.

Chair: Dr. Deanna Gates

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Lecture / Discussion Mon, 27 Apr 2020 13:44:40 -0400 2020-04-30T13:15:00-04:00 2020-04-30T14:15:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Xianglong Wang (May 5, 2020 1:00pm) https://events.umich.edu/event/74357 74357-18666221@events.umich.edu Event Begins: Tuesday, May 5, 2020 1:00pm
Location: Off Campus Location
Organized By: Biomedical Engineering

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

Zoom: https://umich.zoom.us/j/99315883529

Biological transport processes often involve a boundary acting as separation of flow, most commonly in transport involving blood-contacting medical devices. The separation of flow creates two different scenarios of mass transport across the interface. No flow exists within the medical device and diffusion governs mass transport; both convection and diffusion exist when flow is present. The added convection creates a large concentration gradient around the interface. Computer simulation of such cases prove to be difficult and require proper shock capturing methods for the solutions to be stable, which is typically lacking in commercial solvers. In this talk, we propose a second-order accurate numerical method for solving the convection-diffusion equation by using a gradient-limited Godunov-type convective flux and the multi-point flux approximation (MPFA) L-Method for the diffusion flux. We applied our solver towards simulation of a nitric oxide-releasing intravascular catheter.

Intravascular catheters are essential for long-term vascular access in both diagnosis and treatment. Use of catheters are associated with risks for infection and thrombosis. Risk management dictates that the catheters to be often replaced on a 3 to 5-day cycle, which is bothersome to both patients and physicians. Nitric oxide (NO) is a potent antimicrobial and antithrombotic agent produced by vascular endothelial cells. The production level in vivo is so low that the physiological effects can only be seen around the endothelial cells. The catheter can incorporate a NO source in two major ways: by impregnating the catheter with NO-releasing compounds such as S-nitroso-N-acetyl penicillamine (SNAP) or using electrochemical reactions to generate NO from nitrites. We applied our solver to both situations to guide the design of the catheter.

Lung edema is often present in patients with end-stage renal disease due to reduced filtration functions of the kidney. These patients require regular dialysis sessions to manage their fluid status. The clinical gold standard to quantify lung edema is to use CT, which exposes patients to high amounts of radiation and is not cost efficient. Fluid management in such patients becomes very challenging without a clear guideline of fluid to be removed during dialysis sessions. Aggressive fluid removal can cause both exacerbations of congestive failure and hypotension resulting from low blood volume.

Recently, reverberations in ultrasound signals, referred to as “lung ultrasound comets” have emerged as a potential quantitative way to measure lung edema. Increased presence of lung comets is associated with higher amounts of pulmonary edema, higher mortality, and more adverse cardiac events. However, the lung comets are often counted by hand by physicians with single frames in lung ultrasound and high subjectivity has been found to exist among the counting by physicians. We applied image processing and neural network techniques as an attempt to provide an objective and accurate measurement of the amount of lung comets present. Our quantitative results are significantly correlated with a few clinical parameters, including diastolic blood pressure and ejection fraction.

Co-Chairs: Dr. Joseph Bull and Dr. Alberto Figueroa

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Lecture / Discussion Tue, 21 Apr 2020 13:16:12 -0400 2020-05-05T13:00:00-04:00 2020-05-05T14:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
Ph.D. Defense: Kevin Hughes (May 8, 2020 10:00am) https://events.umich.edu/event/74436 74436-18714560@events.umich.edu Event Begins: Friday, May 8, 2020 10:00am
Location: Off Campus Location
Organized By: Biomedical Engineering

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

Blue Jeans Link: https://bluejeans.com/302652230

A variety of immunological disorders are characterized by inappropriate responses to innocuous protein. This is particularly relevant in autoimmune disease, allergy, and transplant rejection. For these, the therapeutic options that exist are minimal or involve broadly immunosuppressive regimens which are often characterized by undesirable side effects. This dissertation highlights advances in the design of a biodegradable poly-lactide-co-glycolide (PLG) nanoparticle (NP) platform to provide antigen-specific tolerance in these disease models.

Strategies to incorporate multiple antigens conjugated to bulk PLG were investigated in a murine model of multiple sclerosis with the observation that a minimum antigen loading of 8µg of antigen per mg of nanoparticle was sufficient to induce maximally observed efficacy. Insights gathered from development of these particles were critical to the design of experiments related to food allergy in mice. Importantly, we demonstrate that it is possible to delivery peanut extract via nanoparticles intravenously without induction of anaphylactic response. Prophylactic and therapeutic administration of particles resulted in improved clinical outcomes and reduction in Th2 markers, including IL-4, IL-5, and IL-13. Interestingly, administration of PLG NPs to deliver allergen did not induce skewing of immunological responses towards Th1/Th17, which is a common approach to treat allergy in pre-clinical models and certain clinical immunotherapy regimens. Studies in a murine model of allogeneic skin transplant rejection demonstrated that the method of incorporation of antigen into the PLG NP resulted in statistically significant delay in graft rejection. These studies also demonstrated shortcomings in the platform’s ability to completely prevent rejection, which we hypothesize is the result of an inability to prevent direct rejection.

Development of FasL-conjugated implantable polymeric discs provided an immunologically privileged site on which to transplant islet cells, which may represent an opportunity to supplement tolerogenic therapies like our PLG NPs. A similar polymeric, implantable technology was designed to enable analysis of the function of inflammatory immune cells, a novel finding which has provided a method to monitor disease progression and response to therapy in a murine model of multiple sclerosis. Collectively, this work has provided several novel strategies to improve polymeric nanoparticle therapies and an implantable, biodegradable platform that shows promise as a companion diagnostic for therapies that impact immune function, including PLG NPs.

Chair: Dr. Lonnie Shea

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Lecture / Discussion Mon, 27 Apr 2020 13:54:09 -0400 2020-05-08T10:00:00-04:00 2020-05-08T11:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
RNA Innovation Seminar, Jeffery Twiss, MD, PhD, Professor, Interim Departmental Chair, SmartState Chair in Childhood Neurotherapeutics, University of South Carolina (June 15, 2020 4:00pm) https://events.umich.edu/event/73583 73583-18263274@events.umich.edu Event Begins: Monday, June 15, 2020 4:00pm
Location: Taubman Biomedical Science Research Building
Organized By: Center for RNA Biomedicine

Jeffery Twiss, MD, PhD, Professor, Interim Departmental Chair, SmartState Chair in Childhood Neurotherapeutics, University of South Carolina

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Lecture / Discussion Thu, 05 Mar 2020 08:43:23 -0500 2020-06-15T16:00:00-04:00 2020-06-15T17:00:00-04:00 Taubman Biomedical Science Research Building Center for RNA Biomedicine Lecture / Discussion lecture
PhD Defense: Matthew S. Willsey (June 29, 2020 10:00am) https://events.umich.edu/event/74994 74994-19128257@events.umich.edu Event Begins: Monday, June 29, 2020 10:00am
Location: Off Campus Location
Organized By: Biomedical Engineering

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

Zoom: https://umich.zoom.us/j/91278019863

Many diseases and injuries irreparably harm the brain or spinal cord and result in motor paralysis, widespread sensory deficits, and pain. Often, there are no treatments for these injuries, and therapies revolve around rehabilitation and adapting to the acquired deficits. In this work, we investigate brain machine interfaces (BMIs) as a future therapy to restore sensorimotor function, use BMIs to understand sensorimotor circuits, and use novel imaging algorithms to assess structural damage of somatosensory inputs into the brain.

Brain-controlled robotic arms have progressed rapidly from the first prototype devices in animals; however, these arms are often slow-moving compared to normal hand and arm function. In the first study, we attempt to restore higher-velocity movements during real-time control of virtual fingers using a novel feedforward neural network algorithm to decode the intended motor movement from the brain. In a non-human primate, the neural network decoder was compared with a linear decoder, the ReFIT Kalman filter (RFKF), that we believe represents the state-of-the-art in real-time finger decoding. The neural network decoder outperformed RFKF by acquiring more targets at faster velocities. This neural network architecture may also provide a blueprint for additional advances.

Somatosensory feedback from robotic arms is an important step to improve the realism and overall functioning. The use of somatosensory thalamus was investigated as a site of implantation for a sensory prosthesis in subjects undergoing awake deep brain stimulation surgery (DBS). In this study, electrical stimulation of the thalamus was performed using different stimulation patterns and the evoked sensations were compared. We found that the sensations evoked by bursting (a burst of pulses followed by a rest period) and tonic (regularly repeating pulses) stimulation were often in different anatomic regions and often with differing sensory qualities. These techniques for controlling percept location and quality may be useful in not only in BMI applications but also in DBS therapies to better relieve symptoms and avoid unwanted side effects.

Given the importance of sensory integration in motor functioning, the third study investigated the impact of a pharmacological perturbation on somatosensory content in primary motor cortex measured with Utah arrays implanted in two NHPs. Specifically, during continuous administration of nitrous oxide (N2O), somatosensory content was assessed by using the neural activity in primary motor cortex to classify finger brushings with a cotton-tip applicator. N2O degraded but did not eliminate somatosensory content in motor cortex. These findings provide insight into N2O mechanisms and may lead to further study of somatosensory afferents to motor cortex.

A debilitating facial pain syndrome, called trigeminal neuralgia (TN), is thought to be caused by vascular compression of the sensory root that provides somatosensory feedback from the face. In this final study, magnetic resonance diffusion tensor imaging was used to assess the structural damage of this sensory root. In a retrospective manner, we developed and tested an algorithm that predicted the likelihood of pain relief after surgical treatment of TN. This algorithm could help select patients for surgery with the best chance for pain relief.

Together, these studies advance BMI technologies that attempt to restore realistic function to those with irreparable damage to sensorimotor pathways. Furthermore, using BMIs and novel imaging, this work provides a better understanding of sensorimotor circuits and how sensory pathways can be damaged in disease states.

Co-Chairs: Parag G. Patil and Cynthia A. Chestek

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Lecture / Discussion Thu, 18 Jun 2020 15:24:23 -0400 2020-06-29T10:00:00-04:00 2020-06-29T11:00:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
PhD Defense: Daniel Quevedo (July 1, 2020 9:30am) https://events.umich.edu/event/74977 74977-19118435@events.umich.edu Event Begins: Wednesday, July 1, 2020 9:30am
Location: Off Campus Location
Organized By: Biomedical Engineering

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

BlueJeans: https://bluejeans.com/863787871

Nanomedicine- where a therapeutic is loaded into nanoparticles to increase therapeutic efficiency and improve patient outcomes- has long had the potential to revolutionize medicine. With all of their promise, nanoparticle carrier technologies have yet to make a significant clinical impact, emphasizing the need for new technologies and approaches. In this dissertation, electrohydrodynamic (EHD) co-jetting was used to develop various methods to create novel Synthetic Protein Nanoparticles (SPNPs), which were then applied to the delivery of therapeutic enzymes, and characterized using a microfluidic technique. It was found that SPNPs can be made from various proteins, such as Human Transferrin, Hemoglobin, and others, and that various macromers can be selected, such as a stimuli responsive NHS-Ester based macromer that can detect oxidative environments and show signs of degradation within 30 minutes of being taken up by HeLa cells. SPNPs were then loaded with medically relevant enzymes, such as the antioxidant enzyme catalase. The enzymes showed high activity retention rates, with catalase SPNPs maintaining up to 82% of their original enzymatic activity. Additionally, antibody-targeted catalase SPNPs were able to protect up to 80% of REN cells in an inflammatory disease model. Next, an electrokinetic microfluidic system was adapted for the characterization of SPNPs based on their protein composition and anisotropy, and was able to differentiate bicompartmental particles made from two different proteins from single compartment SPNPs made of an equivalent isotropic mixture of the same two proteins, with a voltage difference of 900 V between the two particle types, in contrast to the 50 V step sizes possible in these systems. Finally, preliminary work was conducted on using a small targeting molecule, meta-acetylenbenzylguanidine (MABG), for the treatment of neuroblastoma, and a system for validating MABG targeting in SK-N-BE(2) cells (a neuroblastoma cell line) was developed. Work done in this dissertation presents the development of multifunctional protein nanocarriers and lays the groundwork for the targeted delivery of active therapeutics using these particles.

Chair: Dr. Joerg Lahann

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Lecture / Discussion Thu, 18 Jun 2020 15:24:54 -0400 2020-07-01T09:30:00-04:00 2020-07-01T10:30:00-04:00 Off Campus Location Biomedical Engineering Lecture / Discussion BME Logo
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/.

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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/

––
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/.

––

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/

––
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