New approaches for uncovering the role of energy metabolism in health and disease: Dr. Denis Titov, Molecular and Cell Biology Department, UC Berkeley

Seminar: Biosystems and Computational Biology: CS | April 4 | 4-5 p.m. | 114 Morgan Hall

 Center for Computational Biology, Nutritional Sciences and Toxicology

Over the last century, many studies have demonstrated that calorie restriction (i.e. decreased food intake) and exercise cause lifespan extension in model organisms and decrease human mortality from age-associated diseases. Many physiological changes in response to calorie restriction and exercise have been identified, however, it is still unknown which specific changes in metabolism drive these beneficial effects on aging. To address this question, I am using two parallel approaches. First, I am developing a suite of novel genetically encoded tools for manipulation of key metabolic parameters (e.g. NADH/NAD+ ratio) in live cells that will allow us to establish the causal relationships between specific changes in metabolism that are observed with calorie restriction or exercise and their effects on lifespan and other age-associated phenotypes. Second, I am building novel kinetic models of energy metabolism that will allow us to characterize the regulation of energy metabolism pathways by making quantitative predictions of reaction rates and metabolite concentrations in live cells. Together, these studies aim to uncover novel mechanisms of regulation of energy metabolism and their role in the aging process.

Denis Titov is an Assistant Adjunct Professor in the MCB Department at UC Berkeley. His lab works on studying the role of metabolism in aging using a combination of experimental and modeling approaches. Prior to coming to Berkeley in 2018, Denis did his postdoctoral research with Prof. Vamsi Mootha at Massachusetts General Hospital/ Harvard Medical School where he developed the first genetically encoded tools for compartment-specific manipulation of redox cofactor ratios and used these tools to demonstrate that maintenance of NADH/NAD+ ratio, not ATP synthesis, is the essential function of mitochondrial electron transport chain that is required for mammalian cell proliferation. Denis did his Ph.D. at Johns Hopkins University, working with Prof. Jun Liu, where he identified the molecular target of antiproliferative natural product triptolide that remained a mystery for more than 30 years since its discovery. Denis did his early training in Russia, majoring in Chemistry from Novosibirsk State University., 510-666-3342