Ph.D Candidate, Rutgers-RWJMS
My project is mainly focusing on targeting caner metabolism
One fundamental change in oncogenesis is the alteration of glucose metabolism. With few exceptions, cancer cells exhibit aerobic glycolysis, or the Warburg effect. As a result, reduction in the flux of pyruvate into mitochondria prevents the complete oxidation of glucose. Significant amount of glycolytic intermediates can be shunted to pathways for the production of NADPH and building blocks of macromolecules such as protein, lipid, and nucleic acids. This mode of metabolism is essential for the cellular biosynthesis essential for proliferation of cancer cells. Mitochondrial uncoupling is a process which leads to proton influx across the mitochondrial inner membrane without passing through mitochondrial FoF1-ATP synthase. This process de-couples mitochondrial oxidation from ATP synthesis, leading to a futile oxidation of acetyl-CoA (pyruvate equivalent in mitochondria) without generation of ATP. As pyruvate influx to mitochondria is tightly coupled to cellular energetic needs, we hypothesize that safe mitochondrial uncouplers would dramatically increase pyruvate influx to mitochondria for complete oxidation, thereby effectively antagonize the anabolic effect of the Warburg effect in pancreatic cancer cells.