Seminars

Peroxisome proliferator-activated receptor alpha (PPARα) is a well-characterized nuclear receptor widely recognized as a master regulator of metabolic responses to nutrient deprivation. Under nutrient-deprived conditions, free fatty acids released from adipose tissue lipolysis are delivered to the liver, where they act as endogenous ligands for PPARα. Upon activation, PPARα promotes lipid catabolism and gluconeogenesis, thereby conserving energy and maintaining metabolic homeostasis during energy-limiting states. While most studies have focused on PPARα's roles in glucose and lipid metabolism, its relationship with protein metabolism remains less well understood. Recently, our group identified a novel role for PPARα in directly activating autophagy, independent of the mTOR pathway. In addition, we demonstrated that PPARα activation represses the transcriptional activity of coagulation factor genes Fga and F11 through direct interaction with promoter-proximal Inverted Repeat-1 (IR-1) Farnesoid X Receptor (FXR) response elements. Other studies have also reported that PPARα reduces the expression of secreted proteins, including apolipoprotein B, complement components, and coagulation factors, suggesting a broader role for PPARα in protein metabolism. Beyond its known roles in regulating autophagy-related protein degradation and the expression of certain secreted proteins, we identified a novel function of PPARα in orchestrating proteostasis from protein synthesis to degradation in the liver, a central organ for maintaining systemic proteostasis.

Speaker: Gen-Sheng Feng, Professor, University of California, San Diego

Gen-Sheng Feng is Professor of Pathology and Molecular Biology at the University of
California, San Diego. His research program aims at understanding cross-talks and
regulation of signaling pathways in different cell types in health and disease, which was
initiated by his discovery of an SH2-containing tyrosine phosphatase Shp2 (originally
called Syp) in his postdoc studies with the late Tony Pawson. In the past three decades,
his lab is in the driver’s position to decipher how Shp2 promotes signaling through the
RTK-Ras-Erk pathway. This work has led to his most recent discovery of a new type of
vesicle, intercellsome, in cell-cell communication to offset intracellular proliferative
signal deficit.

One current focus of the lab is on elucidating the paradoxical anti-oncogenic effects of
classical oncoproteins in hepatocellular cancer. These findings provide fresh views on
liver cancer initiation and progression, in the dynamic interactions between tumor cells
and the microenvironment. By deciphering multi-faceted roles of the immune ecosystem,
his lab is developing new strategies for combinatorial liver cancer immunotherapy
through coordinated activation of innate and adaptive immune cells.

Dr. Feng got BSc degree in Biology from Hangzhou University, MSc degree in
Immunology, from 2 nd Medical University of Army, Shanghai, and PhD from Indiana
University Bloomington. He received postdoctoral training at the University of Toronto,
Canada. Dr. Feng has published 193 peer-reviewed research papers, reviews and book
chapters. Dr. Feng has served on the editorial boards of MCB, JBC, Hepatology, and
Journal of Hepatology. In 2016, Dr. Feng was elected as Fellow of American Association
for the Advancement of Science (AAAS). Dr. Feng was the President for the Association
of Chinese Americans in Cancer Research (ACACR, 2022-2024) and the President-elect
for the Society of Chinese Bioscientists in America (SCBA).