Martin C. Schmidt, PhD


Dr. Martin Schmidt


Fax: 412-624-1401

521 Bridgeside Point II

450 Technology Drive

Pittsburgh, PA 15219-3143


PhD in Biochemistry, University of California, Berkeley

Research Summary

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.


Research Lab Affiliation


McCartney RR; Garnar-Wortzel L; Chandrashekarappa DG and Schmidt MC. (2016) Activation and inhibition of Snf1 kinase activity by phosphorylation within the activation loop. Biochim Biophys Acta. 11: 1518-1528. |  View Abstract

Chandrashkarappa DG; McCartney RR; O'Donnell AF and Schmidt MC. (2016) The beta subunit of yeast AMP-activated protein kinase directs substrate specificity in response to alkaline stress. Cell Signal. 28: 1881-1893. |  View Abstract

O'Donnell AF, McCartney RR, Chandrashekarappa DG, Zhang BB, Thorner J, Schmidt MC. (2015) 2-Deoxyglucose Impairs Saccharomyces cerevisiae Growth by Stimulating Snf1-Regulated and alpha-Arrestin-Mediated Trafficking of Hexose Transporters 1 and 3. Mol Cell Biol. 35:939-55. |  View Abstract

McCartney RR, Chandrashekarappa DG, Zhang BB, Schmidt MC. (2014) Genetic analysis of resistance and sensitivity to 2-deoxyglucose in Saccharomyces cerevisiae. Genetics. 198:635-46. |  View Abstract

Chandrashekarappa, D. G; McCartney, R. R; and Schmidt, M. C. (2013) Ligand binding to the AMP-activated protein kinase active site mediates protection of the activation loop from dephosphorylation. J Biol Chem. 288: 89-98. |  View Abstract

Mayer, F. V; Heath, R; Underwood, E; Sanders, M. J; Carmena, D; McCartney, R. R; Leiper, F. C; Xiao, B; Jing, C; Walker, P. A; Haire, L. F; Ogrodowicz, R; Martin, S. R; Schmidt, M. C; Gamblin, S. J; and Carling, D. (2011) ADP regulates SNF1, the Saccharomyces cerevisiae homologue of AMP-activated protein kinase. Cell Metab. 14: 707-714. |  View Abstract

Rubenstein, E. M; McCartney, R. R; Zhang, C; Shokat, K. M; Shirra, M. K; Arndt, K. M; and Schmidt, M. C. (2008 ) Access Denied: Snf1 Activation Loop Phosphorylation is Controlled by Availability of the Phosphorylated Threonine 210 to the PP1 Phosphatase. J Biol Chem. 283: 222-230. |  View Abstract