Vytas A. Bankaitis

My laboratory is interested in the regulatory interfaces between novel lipid-mediated signal transduction pathways and important cellular functions. The focus of our work is the phosphatidylinositol/ phosphatidylcholine transfer proteins (PITPs), a ubiquitous but enigmatic class of proteins. Ongoing projects in the laboratory derive from a multidisciplinary approach that encompasses biochemical characterization of novel members of the metazoan PITP family, and the application of genetic, molecular and biophysical approaches to detailed structural and functional analyses of PITPs. The laboratory breaks down into two groups: a group that studies the mechanism of function of fungal and plant PITPs, and a group that generates knockout mice and analyzes the function of specific PITP isoforms in the mammal. Our collective evidence indicates that PITPs coordinate key interfaces of lipid-driven metabolic reactions and intracellular signaling pathways in both yeast and mammals. Inappropriate regulation of these interfaces compromises membrane trafficking events, growth factor receptor function, cell growth control, and regulation of key developmental pathways. Because defects in any one of these pathways define recognized mechanisms cancer-potentiating mechanisms, PITPs represent essentially unstudied regulators whose dysfunction is likely to influence the activities of cellular processes required for cellular homeostasis. Of additional interest is our recent finding that one of our PITP-deficient mouse lines potentially provides a unique model for chylomicron retention disease, hypoglycemia and brain inflammatory disease. Relevant approaches that the laboratory employs include: molecular biology, protein and lipid biochemistry, confocal and electron microscopy, mouse gene knockout technology, and classical and molecular genetics. The lab is also developing new approaches for rapidly and confidently identifying the first small molecule inhibitors directed against target PITPs of interest and other key enzymes of lipid metabolism.