Research Focus: Our research group studies prostate and bladder cancer focusing on key clinical challenges encompassing cancer stem cells, metastasis, therapeutic resistance and methods to overcome resistance such as immunotherapy. To model clinical disease, we use a multipronged approach including the application of novel genetically engineered mouse (GEM) models of cancer, patient derived xenograft (PDX) models and ex-vivo culture systems.
Current Areas of Interest
1) Overcoming treatment resistant in bladder cancer through immune checkpoint blockade. The recent FDA approval of nivolumab (Opdivo) for locally advanced or metastatic urothelial cell carcinoma (UCC) in patients failing chemotherapy has provided rationale for the preclinical modeling of where and when PD-1 checkpoint blockade is effective. To do this we have developed a new immune competent mouse model of muscle invasive bladder cancer (MIBC) allowing the evaluation of anti-PD-1 therapy alone and in combination with cisplatin based chemotherapy. Studies are focusing on defining which cell populations are responsive and which are potentially resistant using cell lineage and mutational epitope mapping. Modeling studies will closely parallel current clinical trials in bladder cancer being conducted at Mount Sinai.
2) Understanding the role of cancer dormancy in treatment resistant prostate cancer. Front line therapies for prostate cancer are typically highly effective however a significant portion of men will progress to castration resistant prostate cancer (CRPC) and metastasis. Using genetically engineered mouse (GEM) models we strive to understand to contribution of cellular quiescence and dormancy towards therapeutic resistance and clinical recurrence. To do this we have generated GEMs with prostate specific deletion of the PTEN tumor suppressor engineered an H2B-GFP label retaining system allowing for the quantitative and qualitative analysis of dormant prostate cancer cells. This system will help determine why cancer patients recur after many years of being clinically asymptomatic.