We investigate the mechanism of DNA repair and DNA damage response that supports hematopoiesis and lymphocyte development and suppress oncogenic transformation. Specifically, we are interested in understanding the DNA double-strand break repair pathway that mediates the assembly and subsequent modification of the lymphocyte antigen receptor genes. Misrepair of these programmed DNA double-strand breaks can lead to chromosomal translocations and eventually lymphoid malignancies. Current areas of investigation in our laboratory include the identification of novel regulations and new factors that contribute to high fidelity and high efficient repair. The majority of anti-cancer chemotherapy damages DNA and induces the DNA damage response to eliminate the malignant cells. In addition, we also wish to understand the tissue-specific responses to DNA damage and genotoxic cancer therapy to minimize normal tissue damage. We are also interested in DNA repair in special genomic regions, such as ribosome DNA regions. Although the repair pathway and the response to DNA double-strand breaks are conserved, the tissue-specific developmental program often dictates the outcome of disrepair and contributes to selective toxicity during hematopoiesis. Our studies provide a physiological view of DNA repair and DNA damage response during development and upon therapy.
Shan Zha, MD, PhD