Fajun Yang, Ph.D.
Associate Professor, Department of Medicine (Endocrinology)
Associate Professor, Department of Developmental & Molecular Biology
The sterol regulatory element -binding proteins (SREBP) are critical regulators of both fatty acid and cholesterol homeostasis. The SREBP proteins are synthesized as inactive precursors that are tethered to the endoplasmic reticulum membrane. In response to decreased cellular levels of sterols or insulin, SREBP precursors are proteolytically processed to mature forms of transcription factors that migrate into the nucleus and activate transcription of target genes, which encode the rate-limiting enzymes in synthesizing fatty acids and cholesterol. Dr. Yang's laboratory is interested in understanding how SREBP-mediated transcription is regulated and the molecular mechanisms underlying nuclear SREBP degradation. Transcriptional cofactors, such as the Mediator complex and the SIRT1 complex, are involved in regulating the transcription of SREBP target genes. The degradation of mature SREBP transcription factors is regulated by post-translational modifications, such as phosphorylation, acetylation and deacetylation, which is controlled by CDK8, a subunit of the Mediator complex, and SIRT1. Biochemical and genetic approaches are taken to study the role of the Mediator and SIRT1 complexes in SREBP-mediated transcription. With the ultimate goal of identifying targets for preventing or treating metabolic syndrome (including type 2 diabetes, fatty liver disease, hyperlipidemia and hypertension), the aim of his research is to advance knowledge of how lipid homeostasis is regulated at the molecular levels. full bio>>