Presented By: Life Sciences Institute (LSI)
LSI Seminar Series: Wen-Xing Ding, Ph.D., University of Kansas Medical Center
Autophagy and lysosome in liver injury and tumorigenesis
Abstract:
Liver cells can adapt and protect themselves in response to stress by activating cellular protective mechanisms such as autophagy, which is a lysosomal degradation pathway that degrades cellular organelles and/or proteins as well as lipids inside the autolysosomes. To meet the needs of autophagic degradation, it is critical to maintain sufficient numbers of lysosomes to fuse with autophagosomes that form autolysosomes. Lysosomal biogenesis is regulated by the transcription factor EB (TFEB), which is a master transcription regulator of lysosomal biogenesis and autophagy.
Studies from our lab revealed that TFEB is impaired in alcoholic hepatitis and pancreatitis as well as in acetaminophen-induced liver injury. Overexpression of TFEB protects against alcohol and drug-induced tissue damage whereas deletion of TFEB exacerbates tissue damage. Studies from our lab also demonstrated that Nrf2, a transcription factor regulating antioxidant response, promotes liver injury and liver tumorigenesis in autophagy defective livers. More recently, our work suggests that both hyper- and hypo-activation of MTOR are detrimental to the liver resulting in the development of liver tumors. Together, our studies indicate that autophagy and lysosome play critical roles in maintaining liver homeostasis. Approaches to boost autophagy and TFEB pathways, which are often impaired in chronic liver diseases, may be promising for treating and preventing liver disease including alcoholic and non-alcoholic fatty liver diseases, drug-induced liver injury and liver tumorigenesis.
About the Speaker:
Wen-Xing Ding is a professor in the Department of Pharmacology, Toxicology and Therapeutics at The University of Kansas Medical Center. He received his Ph.D. from the National University of Singapore in 2002 and completed his postdoctoral training at the University of Pittsburgh. Ding has devoted his research career to elucidating mechanisms for regulation of cell death and the adaptive response to cellular injury in the liver. Since 2009, his laboratory has been working on the role of autophagy in alcohol- and drug-induced liver injury. They are particularly interested in how autophagy selectively removes cellular damaged/excess organelles, such as mitochondria and lipid droplets in hepatocytes. Ding has published more than 120 papers in peer-reviewed journals, and his work is currently supported by NIAAA and NIDDK.
In addition to research, Ding has demonstrated outstanding leadership for service. He has been a program committee member of ASIP (American Society of Investigative Pathology) and the AASLD (American Association for the Studies of Liver Disease) 2015 annual meeting. He organized several meetings and symposia for EB meeting, AASLD and GRC. He serves as an associate editor for the journal Autophagy and an editorial board member for several journals, including Hepatology, Cell and the American Journal of Pathology. He also serves as an ad hoc reviewer for NIH grants and a standing member of XNDA.
Liver cells can adapt and protect themselves in response to stress by activating cellular protective mechanisms such as autophagy, which is a lysosomal degradation pathway that degrades cellular organelles and/or proteins as well as lipids inside the autolysosomes. To meet the needs of autophagic degradation, it is critical to maintain sufficient numbers of lysosomes to fuse with autophagosomes that form autolysosomes. Lysosomal biogenesis is regulated by the transcription factor EB (TFEB), which is a master transcription regulator of lysosomal biogenesis and autophagy.
Studies from our lab revealed that TFEB is impaired in alcoholic hepatitis and pancreatitis as well as in acetaminophen-induced liver injury. Overexpression of TFEB protects against alcohol and drug-induced tissue damage whereas deletion of TFEB exacerbates tissue damage. Studies from our lab also demonstrated that Nrf2, a transcription factor regulating antioxidant response, promotes liver injury and liver tumorigenesis in autophagy defective livers. More recently, our work suggests that both hyper- and hypo-activation of MTOR are detrimental to the liver resulting in the development of liver tumors. Together, our studies indicate that autophagy and lysosome play critical roles in maintaining liver homeostasis. Approaches to boost autophagy and TFEB pathways, which are often impaired in chronic liver diseases, may be promising for treating and preventing liver disease including alcoholic and non-alcoholic fatty liver diseases, drug-induced liver injury and liver tumorigenesis.
About the Speaker:
Wen-Xing Ding is a professor in the Department of Pharmacology, Toxicology and Therapeutics at The University of Kansas Medical Center. He received his Ph.D. from the National University of Singapore in 2002 and completed his postdoctoral training at the University of Pittsburgh. Ding has devoted his research career to elucidating mechanisms for regulation of cell death and the adaptive response to cellular injury in the liver. Since 2009, his laboratory has been working on the role of autophagy in alcohol- and drug-induced liver injury. They are particularly interested in how autophagy selectively removes cellular damaged/excess organelles, such as mitochondria and lipid droplets in hepatocytes. Ding has published more than 120 papers in peer-reviewed journals, and his work is currently supported by NIAAA and NIDDK.
In addition to research, Ding has demonstrated outstanding leadership for service. He has been a program committee member of ASIP (American Society of Investigative Pathology) and the AASLD (American Association for the Studies of Liver Disease) 2015 annual meeting. He organized several meetings and symposia for EB meeting, AASLD and GRC. He serves as an associate editor for the journal Autophagy and an editorial board member for several journals, including Hepatology, Cell and the American Journal of Pathology. He also serves as an ad hoc reviewer for NIH grants and a standing member of XNDA.
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