Research in the laboratory is focused on genetic, molecular biological, and epidemiological studies of breast, ovarian, and pancreatic cancer with a specific focus on familial/inherited forms of these diseases. Specific projects are as follows:

Characterization of the 17q23 region of amplification in breast tumors. We have determined that the amplified region on chromosome 17q23 in cell lines and breast tumors contains several genes that contribute to the development of breast cancer. Current studies are focused on understanding how the encoded proteins contribute to tumor formation using in vitro studies and in vivo animal models. In addition, methods for blocking the activity of the proteins in tumors are being exlored in an effort to develop new therapies for breast cancer. As this amplicon has recently been implicated in pancreatic cancer similar studies will be undertaken for this tumor type.

Structure-function studies of BRCA1 and BRCA2. The effect of inherited missense mutations on the function of the BRCA1 and BRCA2 breast and ovarian cancer predisposition genes is being evaluated using a series of in vitro functional assays based on the known activity of BRCA1 and BRCA2 in DNA repair and cell cycle control. In addition, efforts are being made to determine which mutations are cancer causing and which are neutral/benign by combining results from these functional assays with epidemiological and genetic data obtained from families harboring these mutations.

The role of BRCA2 in regulation of cell division. We have recently demonstrated that BRCA2 has an important role in regulation of mitosis and cell division. This novel function may help to explain why BRCA2 mutant breast tumors have high levels of genome instability. The mechanism by which BRCA2 regulates this process is being explored.

Genetic Epidemiology. We have collected a large series of high risk breast cancer families for the purpose of identifying polymorphisms (SNPs) that modify the risk of breast cancer in individuals from these families. A similar study of sporadic breast cancer patients from the Mayo Clinic is underway.