Mari Lowe Seminar Series
Title: “Mevalonate Pathway and Cancer Plasticity"
Refreshments will be available.
131 Hill Pavilion
University of Pennsylvania School of Veterinary Medicine
380 S University Avenue, Philadelphia, PA 19104
About Dr. Astsaturov's Research: "My lab opened in 2009 endowed with the challenge to define the critical regulators of tumor cell response to drugs targeting EGFR (Astsaturov, Science Signaling, 2010). From this initial task which ultimately led to 2 clinical trials in patients with head and neck and lung cancers, 3 NIH grants and 6 papers, we define a previously overlooked step of C4-demethylation in the enzymatic cascade of cholesterol biosynthesis. Inactivation of SC4MOL or NSDHL involved in the oxidative demethylation at C4 leads to dramatic alteration in the vesicular trafficking of the endocytosed EGFR and sensitizes cancer cells to EGFR inhibitors (Sukhanova, Cancer Discovery, 2013).
"Following this initial lead, Linara Gabitova took on the challenge to pinpoint the mechanism executing such a dramatic effect of accumulating C4-methylated sterols. She found that LXR alpha was the critical effector triggered by these sterol species, so that activation of LXR can be used to deregulate cholesterol turnover in cancer synergistically with EGFR antagonists in in the KRAS-driven tumors (Cell Reports, 2015).
"Our current interests are focused on pancreatic cancer where KRAS is the causative oncogenic mutation. We are looking for metabolic vulnerabilities in the cholesterol pathway as well as developing innovative drug delivery tools to improve lives of the patient with this devastating and thus far recalcitrant cancer."