My research is focused on molecular mechanisms of cancer therapy and mechanism of chemoresistance. Research is focused on uncovering mechanisms that account for the curability of testicular germ cell tumors in order to apply this knowledge to the design of novel therapies for common solid tumors refractory to current therapy. Other interests include the concept of induced differentiation therapy and the identification of mechanistic links between stem cell pluripotency and cancer.
My lab has made several key contributions to understanding transcriptional mechanisms linked to the retinoic acid induced differentiation of testicular cancer and to the curability and resistance of testicular cancer through global gene expression and genome-wide analysis. This includes our finding that testicular cancer cells display a hyperactive p53 response to chemotherapy that is tightly linked to their curability. The goal of the lab is to leverage this information toward success in treating other solid tumors including glioblastoma and breast cancer.
Recently my lab has made the discovery that testicular germ cell tumors, even those resistant to cisplatin, highly overexpress DNA methyltransferase 3B (DNMT3B) and have increased sensitivity to very low doses of DNA demethylating agents compared to somatic cancer cells. This work has provided the rationale for ongoing phase I and planned phase II clinical trials being conducted with collaborators at Indiana University Medical School. Our current working model is that testicular cancer cells possess unique epigenetic states that are tightly linked to the biology of this disease. Understanding these mechanisms will inform epigenetic-based therapies for refractory testicular cancers and other solid tumors.