In 1989, he joined the faculty at Dartmouth. Cell death by a pathway known as apoptosis occurs as a physiological process required for the normal homeostasis of a multicellular organism. Of particular interest to cancer is the observation that certain oncogenes and tumor suppressor genes can either enhance or prevent apoptosis. There are many inducers of apoptosis such as anticancer agents, immune signals, and removal of growth factors that activate multiple pathways converging on a final common execution phase. This research program is aimed at understanding these pathways as an approach to identifying novel targets for improving therapeutic outcome.
Experimental tools involve predominantly molecular biology and cell culture.
We have identified and cloned an endonuclease potentially involved in the DNA fragmentation associated with apoptosis. Transfection of the endonuclease into cells induces apoptosis, and current experiments are designed to understand the structure of the endonuclease and the regulation of its catalytic activity. Future experiments will genetically delete expression to define its role in development and apoptosis. DNA fragmentation results from a cascade of proteolytic cleavage events which, in turn is activated by protein phosphatase 1. The current hypothesis is that apoptosis is regulated by an imbalance between specific intracellular signal transduction pathways which impact on the activation of protein phosphatase 1.