Genomic Strategies for the Study of Cellular Proliferation and Disease Phenotypes

Our laboratory focuses on:

• The gene regulatory mechanisms controlling cellular proliferation and cell fate
• The use of genomic-scale measures of gene expression to provide characterizations of disease phenotypes

This work can ultimately lead to personalized treatment of cancer patients, and similar methods can be developed for other diseases, including cardiovascular disease.

The gene regulatory events controlling cell proliferation are critical to normal development and to maintenance of tissue homeostasis. These events are often disrupted in the development of tumors.

Our work specifically focuses on the role of the retinoblastoma tumor suppressor protein (Rb) in controlling the E2F transcription factor activities in the cell. E2Fs are critical for the expression of a large number of genes encoding proteins that carry out DNA replication, cell cycle progression, and mitosis.

We have also focused on the control of the Myc oncoproteins and the events that connect the Myc and Ras signaling pathways together with the Rb/E2F pathway in the control of cell proliferation and cell fate.

Finally, focusing on the use of DNA microarray analysis to provide genome-scale measures of gene expression, we have developed strategies to characterize the activity of these various oncogenic signaling pathways in tumors, including the use of this information to guide the use of various cancer therapeutics. In parallel, we have made use of similar technology to develop predictive tools of disease outcome and the response to conventional chemotherapeutic drugs.

The long-term goal is the use of these assays to provide a strategy for personalized treatment of cancer patients. Similar strategies can be developed for other disease states, including various aspects of cardiovascular disease.