Dr. Zhang’s research focuses on 1) defining and characterizing deregulated pathways with therapeutic relevance in subsets of human cancers, and 2) developing and implementing biomarker-driven therapeutics into patient-based therapeutic trials.He aims to identify the DNA damage repair pathways that metastatic prostate cancers rely on and then assess the therapeutic potential of targeting these pathways. Preliminary data indicates that blocking key proteins in DDR pathways with PARP inhibitor, DNA-PK inhibitor or BRCA1 shRNA sensitized metastatic prostate cancer cells to DNA damaging chemotherapy drugs. The synergistic combinations are being tested in metastatic prostate cancer mouse models.Secondly, Dr. Zhang is evaluating r-H2AX as a prognostic or predictive marker.Unrepaired DNA single strand breaks will be converted to double strand breaks (DSB) during DNA replication, and r-H2AX is a well-known marker for DNA DSB. High levels of r-H2AX expression in prostate cancers would correlate with diminished DNA repair pathways and therefore high mutation rates. Dr. Zhang and colleagues will develop a scoring system for r-H2AX expression by immunohistochemistry and correlate that with patients’ clinical outcomes. Based on initial results, the value of r-H2AX can be further evaluated in larger patient cohorts with multi-variant analysis. Assays also can be developed to detect r-H2AX in circulating tumor cells.