My laboratory has studied genome instability in the form of mutations, loss of heterozygosity, and chromosomal rearrangements, and their role in tumorigenesis. These genetic changes result from endogenous processes, such as DNA replication failure, oxidative metabolism and age-related telomere erosion, as well as exposure to exogenous agents, such as chemotherapeutic chemicals, and radiation. A broad array of DNA repair mechanisms addresses this damage in human cells and maintains genome stability. We have focused most directly on homology directed repair (HDR), which is essential for life in humans, indicative of its critical role in the repair of endogenous DNA damage. HDR factors, such as BRCA1 and BRCA2 are also important tumor suppressors reflecting their prominent role in genome stabilization. Many cancers are found to be defective for BRCA1 or BRCA2. Intriguingly, reducing the level of another DNA repair protein, RAD52, in BRCA-defective tumor cells is lethal but has little effect on normal cells. This “synthetic lethality” indicates that RAD52 would be an excellent target for chemotherapeutic assault as it would kill tumors without affecting normal tissue. Such a strategy could revolutionize cancer treatment by replacing drugs that cause dangerous side effects with drugs that are more targeted to the tumor and much better tolerated. However, the same attributes that make RAD52 an excellent chemotherapeutic target also make it difficult to develop drugs against, as killing BRCA-defective cells and having little effect on normal cells provide little opportunity for study. This is addressed by our recent discovery that RAD52 repairs broken chromosomes in budding yeast where this repair is not required for viability. This provides the opportunity to distinguish between compounds that affect RAD52 function and general cellular poisons. This system is being used for the high-throughput screening of compound libraries for inhibitors of RAD52 function, and to study their effects at the molecular level in order to develop them into safe and effective chemotherapeutic drugs.

Fellowship

Postdoctoral Fellowship - Department of Genetics and Development, Columbia College of Physicians and Surgeons, Columbia University, NY, NY - 1993

PhD - Albert Einstein College of Medicine, Bronx, NY – 1987
PhD Candidate - University of South Carolina, Columbia, SC, - 1983
BA - University of Delaware, Newark, DE- 1982