Tue, October 15, 2024 11:00 AM - Tue, October 15, 2024 1:00 PM at 162 Food Safety & Toxicology Building
*The Institute for Integrative Toxicology presents Dr. John Clarke, Washington State University, to speak on, “Microcystin-LR Hepatotoxicity in Healthy Versus Metabolic Dysfunction-Associated Steatotic Liver Disease Rodents,” on Tuesday, October 15, 2024, at 11:00 a.m. in 162 Food Safety and Toxicology Building.
Microcystin-LR (MCLR) is a potent hepatotoxin that may play a role in the progression of metabolic dysfunction- associated steatotic liver disease (MASLD) to more advanced stages, such as metabolic dysfunctionassociated steatohepatitis (MASH) and hepatocellular carcinoma (HCC). The Clarke lab has been investigating whether there is differential susceptibility to MCLR exposure and toxicity between healthy rodents and those with MASLD. Our findings suggest that while healthy animals exhibit more significant overall changes in gene expression following MCLR exposure, rodents with pre-existing MASLD show increased vulnerability to MCLR-induced fibrotic and carcinogenic effects in the liver. Cell type-specific analysis reveals that these responses are primarily driven by MCLR's effects on hepatocytes and stellate cells. These findings indicate that MCLR could be an underrecognized factor contributing to the progression of MASLD and the development of HCC.
Dr. John Clarke is an Associate Professor and Vice-Chair in the Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences at Washington State University Health Sciences Spokane. He received his B.S. in biology from Brigham Young University-Idaho, and received his Ph.D. in Molecular and Cellular Biology from Oregon State University under the mentorship of Dr. Emily Ho. He completed a postdoctoral fellowship in the department of Pharmacology and Toxicology at the University of Arizona with Dr. Nathan Cherrington. His research has been funded by the Department of Defense, the NIH National Institute for Environmental Health Sciences (NIEHS), and the NIH National Center for Complimentary and Integrative Health. This includes a highly competitive K99-R00 award from NIEHS. He is currently co-investigator in the Center of Excellence for Natural Product-Drug Interaction research and is PI for a prestigious NIEHS Outstanding New Environmental Health Scientist (ONES) R01 grant. His research interests and expertise are focused on elucidating the mechanisms of inter-individual variability in xenobiotic metabolism, disposition, and toxicity. This includes research with environmental contaminants and pharmaceuticals. He is the Past-President of the Pacific Northwest Association of Toxicologists, which is a regional chapter of the Society of Toxicology. He also serves as a Councilor in the Drug Metabolism and Disposition Division of the American Society for Pharmacology and Experimental Therapeutics. He serves as a standing member of the NIH Drug and Biologic Disposition and Toxicity study section. He was the recipient of the 2023 Society of Toxicology Achievement Award.
*Fulfills seminar requirements for the Environmental and Integrative Toxicological Sciences Graduate Programs. Seminars that fulfill this requirement are archived at: https://iit.msu.edu/training/eits/recent-seminar-list.html.