Overview

We are studying factors that regulate how cells multiply, change and die, especially those involved in early stage colon cancer. A major focus is understanding how hormones control renewal of the intestinal epithelium. We also are studying factors that regulate gene expression in lymphoma cells.

The normal intestinal epithelium is replaced every three days or so. Turnover of the epithelium depends upon careful control of a number of cellular processes, including proliferation, differentiation, cellular motility and interaction of the cells with each other and the extracellular matrix.

In the colon, the principle regulators of these processes are transforming growth factor-beta (TGFβ) and peroxisome-proliferator activated receptor-gamma (PPARγ).

We have initiated a comprehensive genomic analysis of normal intestinal epithelial cells in culture as well as genetically engineered mice that are at high risk for colon cancer. Our data indicate that there is an astonishing degree of synergy between TGFβ and PPARγ signaling at the genomic level. Furthermore, both TGFβ and PPARγ control cell proliferation and cell motility by mechanisms that may involve convergence on downstream signal transduction pathways.

In addition, we have a long standing interest in glucocorticoid regulation of gene expression in lymphoma cells. We have studied this process for many years, and our present interest is in using machine learning statistical approaches to discern genetic regulatory networks that control and coordinate the process whereby glucocorticoids control progression through the G1 phase of the cell cycle.