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Andrea Johnston

Link to Pubmed Publications

LSU, School of Veterinary Medicine, Department of Veterinary Clinical Sciences


Project Title

Phosphoglycerate mutase 5 (PGAM5) in the regulation of hepatic lipid metabolism and carcinogenesis.


Mentors

Samithamby "Jey" Jeyaseelan, Ph.D., Louisiana State University, School of Veterinary Medicine, Department of Pathobiological Science

Dr. Jacqueline Stephens, Ph.D., Louisiana State University, Pennington Biomedical Research Center


Funding Period

Project (May 1, 2021 - February 28, 2024)


Biosketch

Dr. Johnston grew up in Hopkinton, MA. She earned her B.S. in Microbiology and Veterinary Sciences from the University of Arizona and her D.V.M. from Tufts University School of Veterinary Medicine. She completed her residency in Small Animal Internal Medicine at Cornell and earned her Ph.D. in Molecular Biology from UT Southwestern in Dallas. Dr. Johnston is currently an assistant professor at LSU School of Veterinary Medicine, where she is investigating the role of mitochondrial membrane protein PGAM5 in hepatocellular carcinoma.


Abstract


The broad objective of this project is to determine whether changesin mitochondrial metabolism mechanistically influence the transition fromnon-alcoholic fatty liver disease (NAFLD) to hepatocellular carcinoma (HCC). NAFLD isemerging as a leading cause of HCC. HCC survival outcomes are poor. Defining the bioenergetic pathophysiology of NAFLD and its progression to HCC will identify new biomarkers and therapeutic targets. The mitochondrial membrane proteinphosphoglycerate mutase 5 (PGAM5) regulatesan array of mitochondrial homeostatic pathways. Recent research showsthat depletion of PGAM5 preventsboth high fat diet (HFD) induced obesity and the progression of HCC. The proposedresearch will test the hypothesisthat distinct mitochondrial metabolic pathways are responsible for these effects.A liver specificknockout mouse will be generatedtodetermine whetherhepatocyte specific loss of PGAM5 will inhibitsteatosis in a HFD model.Single cell RNA sequencing of a human HCC cell linewill determine if PGAM5 depletion alters gene expression associated with hepatic lipid metabolism. HCC spheroids will be used to characterize how loss of PGAM5 modulatesmitochondrial respiration and glycolysisin a steatosis model. Two specific aims are proposed: Aim 1 will determine whether PGAM5 knockout inhibits hepatocellular steatosis. Aim 2 will determine whether PGAM5 deletion alters mitochondrial metabolism in HCC leading to increased reactive oxygen speciesproduction.