We pioneered the concept of redox nucleotide maintenance in protecting cancer cells against tumor-inhibitory oxidative DNA damage.  We use chemistry, molecular/cell biology, pharmacology and transgenic animal models to understand how Nudix pyrophosphatases, such as MTH1, protect cancer cells from oxidative DNA damage by removing 8-oxo-dGTP from the nucleotide pool. We are working on identifying molecular sources of functional 8-oxo-dGTPase redundancy in RAS-driven cancers (pancreatic, lung and colon cancer) in order to inform development of new efficacious, on-target drugs. 

Metastatic castration-resistant prostate cancer (mCRPC) is currently incurable and fatal. We seek to identify new treatment regimens by exploiting dysregulated stress responses associated with progression to castration resistance. Currently, we are working on an NCI-funded project targeting vasodilatory pathways and repurposing FDA approved drugs to identify novel biomarkers and treatments for mCRPC. This project is in the early stages of clinical trial and novel biomarker development.

Prostate cancer is the second most common cancer-related killer of American men. High-risk early stage prostate cancer patients are assigned androgen deprivation therapy. However overweight patients or those with metabolic syndrome are at risk of adverse cardiovascular events from this standard-of-care therapy. We are evaluating alternatives involving FDA-approved safe metabolism-targeting agents to prevent disease progression and improve patient quality of life. This is a bedside-to-bench project using clinical trial response-associated molecular factors to better understand how mitigating metabolic syndrome can delay prostate cancer progression and lead to safer treatments for high-risk early stage patients.