As a physician scientist, the work of my laboratory focuses on basic and translational science aimed ultimately at improving the care of cancer patients. My research centers on two areas, first, discovering new oncogenes that may be targets for cancer therapy, and second, the functions of the BRCA1 and BRCA2 genes, genomic instability, and the relationship between DNA repair lesions and therapy, particularly for triple-negative breast cancer.
We have devised a series of new genome-wide screens to identify novel oncogenic activities that may represent targets for cancer therapy. This screen has identified a number of genes that can play the role of activated RAS in cancer. Some of these genes appear to be amplified and overexpressed in human cancers; we are currently investigating their significance in human malignancy. We are optimistic that some of these new candidate oncogenes may suggest new therapeutic strategies.
Women who have one mutated copy of either the BRCA1 or the BRCA2 gene have very high rates of breast and ovarian cancer. Understanding the functions of these two genes is vital to devise targeted therapies to treat the cancers that arise in these individuals. We have previously shown BRCA1 or BRCA2 loss rapidly results in genomic instability characterized by gross chromosomal rearrangements. In addition, a subset of sporadic breast cancers, the basal-like tumors, bears great similarity to BRCA1-deficient breast cancers, leading to the hypothesis that these tumors share with BRCA1-deficient tumors a defect in genomic integrity maintenance. We are deeply involved in the DF/HCC effort to investigate cisplatin as a treatment of triple-negative breast cancer, a natural outgrowth of our interests in DNA repair defects caused by BRCA1 pathway failure. We helped analyze the DF/HCC clinical trial showing the clinical utility of platinum chemotherapy for sporadic triple-negative breast cancer, and then had a pivotal role in creating a new predictive biomarker of cisplatin response, a biomarker that is now the subject of an ongoing prospective clinical trial. We are also involved in the Dana-Farber/Harvard Cancer Center SPORE in breast cancer in several capacities as well.