Dr. Clarke's laboratory is primarily interested in the use of state-of-the-art molecular, cellular, and bioinformatic technologies to better understand those events that affect the sensitivity, or lack thereof, of breast cancers to cytotoxic (chemotherapy) and hormonal therapies (estrogens, antiestrogens, aromatase inhibitors).

We have begun to identify components of a signaling network that contributes to responsiveness to estrogens (e.g., estradiol, estrone and their sulfates), antiestrogens (e.g., tamoxifen, raloxifene, faslodex), and aromatase inhibitors (e.g., letrozole, arimidex). These studies have implicated several genes that are also expressed in breast cancer specimens from patients. Mechanistic studies of these genes, which include interferon regulatory factor-1, nuclear factor kappa B, X-box binding protein-1, and nucleophosmin, are ongoing.

We are also using gene expression profiling and tissue microarrays to study prognosis and prediction in breast cancer. The goal of these studies is to better determine an individual patient's prognosis and the likelihood that she will respond to specific breast cancer therapies. To support these studies we have assembled a team of engineers, biostatisticians, computer scientists, and mathematicians to develop new and powerful methods to explore the very high dimensional data structures generated in gene expression profiling studies. Our team also includes medical oncologists, pathologists, and cellular and molecular biologists in a fully integrative approach that involves multiple institutions including the Lombardi Comprehensive Cancer Center and several other Georgetown University Departments, the Virginia Polytechnic Institute and State Unversity (Virginia Tech), the University of Edinburgh (Scotland) and the Catholic University of America (Washington DC).