Martin C. Schmidt, PhD

My lab uses baker’s yeast as its model system to study glucose sensing and signal transduction. We have focused on the regulation of the AMP-activated protein kinase (AMPK) known as Snf1 in yeast. In both yeast and human cells, the overall structure of AMPK and the modes of regulation are highly conserved. The speed and synergy of genetic and biochemical studies in yeast make this an ideal system to dissect the regulation of AMPK and apply the new knowledge to human biology. We have found that yeast AMPK regulates glucose transport by controlling which glucose transporters are maintained on the plasma membrane. We are investigating the molecular mechanism by which yeast AMPK controls the localization, function and expression of glucose transporters. In addition we have discovered a novel mechanism by which the glucose analog, 2-deoxyglucose, inhibits glucose metabolism. Yeast and cancer cells share a metabolic strategy called aerobic glycolysis that makes them extra sensitive to 2-deoxyglucose. We are using new genomic technologies to define the mechanism by which cells acquire resistance to this compound. The AMPK enzyme exists in different forms called isozymes. In humans, the AMPK isozymes respond differently to pharmacological agents. We are investigating how the yeast AMPK isozymes differ functionally and mechanistically.