Jeffrey T. Holt, M.D.

Research

We have used genetic and biochemical analysis of human BRCA1 and BRCA2 genes to study the role of these genes in breast, ovary, and prostate cancer. Our access to families with hereditary breast cancer and identification of human cancer cell lines which are hemizygous for the Ashkenazi BRCA1 and BRCA2 mutations have allowed us to demonstrate that BRCA1 functions as a growth inhibitor and tumor suppressor, and that both BRCA1 and BRCA2 function in DNA repair. We have extended these studies to demonstrate that BRCA2 is rapidly induced by estrogen and that a specific phosphorylation site in BRCA2 has a key role in BRCA2 function in DNA repair. We have also developed a novel diagnostic test which identifies BRCA1 and BRCA2 mutations in cancer samples using an antibody-based method and are presently developing simple ways to identify patients without cumbersome and expensive DNA sequencing methods.