George M. Carman, Ph. D.

Regulation of Phospholipid Metabolism/Signaling in Yeast

Dr. Carman’s research utilizes molecular genetic and biochemical approaches to study the regulation of phospholipid metabolism in the yeast Saccharomyces cerevisiae.  Phospholipids are essential molecules that contribute to the structural definition of cell membranes, and participate in the regulation of cellular processes as signaling molecules and as reservoirs of lipid messengers.  The Carman laboratory has made significant contributions to the understanding of phospholipid synthesis in yeast through the purification and characterization of several enzymes and the isolation and characterization of key genes.  The laboratory has played a major role in the discovery that the expression of phospholipid biosynthetic enzymes is regulated by phospholipid precursors and the mineral zinc; and that key enzymes are regulated by membrane- and cytosolic-associated components and by covalent modification by protein kinases. These forms of enzyme regulation have profound effects on membrane phospholipid composition and have important medical implications for understanding the molecular basis for various diseases.  Two research projects are currently funded by grants from the National Institutes of Health.  One project addresses the hypothesis that phosphorylation of phospholipid biosynthetic enzymes represents a mechanism by which pathways of signal transduction mediate phospholipid metabolism.  Key enzymes being studied include choline kinase and CTP synthetase.  Unregulated levels of these two enzymes are common properties of various cancers in humans.  The other project addresses the hypothesis that yeast cells adapt to zinc deficiency by regulating membrane phospholipid synthesis through the expression of several phospholipid biosynthetic enzymes.  Key enzymes being studied include phosphatidylserine synthase, phosphatidylinositol synthase, and phosphatidate phosphatase.