Our research seeks to understand how normal mechanisms that control transcriptional regulation and cellular differentiation are coopted in cancer. We address these broad questions in our research focused on genitourinary cancers using mechanism-based studies, analyses of genetically-engineered mouse models (GEMMs), and state-of-the-art systems biology approaches.

In our studies on prostate cancer, we have developed an extensive series of GEMMs that represent the full spectrum of prostate cancer phenotypes, ranging from pre-invasive to invasive cancer, including castration-resistance, neuroendocrine differentiation, and metastasis. Capitalizing on these GEMMs, we have generated genome-wide transcriptional regulatory networks to pursue cross-species computational analyses of mouse and human prostate cancer, which have led to the identification of master regulators of cancer progression, biomarkers of disease outcome, regulators of drug response and resistance, and drivers of metastasis.

In our studies of bladder cancer, we have developed novel approaches to target gene recombination specifically to bladder urothelium, which have led to the generation of a new series of mouse models of muscle invasive bladder cancer as well as metastatic disease. These have enabled co-clinical trials that are influencing the treatment of patients with high-risk bladder cancer.