R15 CA305114-01 NIH/NCI (Tomida, PI) – 07/2025-06/2028 – Defining novel roles of the DNA repair factor REV7 in p53 signaling and regulation: Over 600,000 Americans die from cancer each year, and an estimated 2,000,000 new cases are diagnosed. Given that p53 is a key tumor suppressor and “guardian of the genome,” defining details of p53 regulation may illuminate mechanisms of its pathogenic gain-of-function. These studies will clarify functions of the REV7-p53 interaction, potentially revealing new therapeutic opportunities directed at p53 regulation.
R15 CA263784-01 NIH/NCI (Tomida, PI) – 07/2021-06/2024 – Synergistic DNA repair genes and sensitivity to radiation therapy in prostate cancer: Metastatic prostate cancer and metastatic castration-resistant prostate cancer acquire resistance to established treatments and progress with profound effects on patient quality of life. Our preliminary findings support the hypothesis that concurrent canonical and alternative NHEJ defects cause hypersensitivity to X-ray in PCa, but simultaneously hyperactivate homologous recombination, resulting in PARPi and VP-16 resistance. Findings from these studies are expected to optimize the prediction of tumor response to radiotherapy in FAM35A-deleted prostate cancer and reveal new gene targets for novel combination therapy.
R03 CA212556-01 NIH/NCI (Tomida, PI) – 08/2017-07/2019 – Loss of novel end joining factor with dysfunction of BRCA1 contributes to treatment resistance: Despite advances in treatment of prostate cancer, metastatic castration-resistant prostate cancer (mCRPC) remains fatal. In the U.S. alone, over 30,000 patients die yearly from mCRPC. Our preliminary findings support FAM35A as a new target for cancer treatment and substantiate its involvement in the end-joining pathway of DNA repair. Results from these (and future) studies are expected to advance mCRPC etiology, elucidate acquisition of metastasis and resistance in PCa and, most importantly, to facilitate discovery of therapeutic and prognostic targets for both chemotherapy and radiation therapy.