Welcome to the Mulholland Lab
The Mulholland research laboratory at The Icahn School of Medicine at Mount Sinai focusses on preclinical modeling of castrate resistant prostate cancer (CRPC) and muscle invasive bladder cancer (MIBC). For CRPC, we use genetically engineered mouse (GEM) models to understand how the lineage content of the cell autonomous tumor evolves in response chemotherapy and androgen receptor inhibition. This has led to the identification of androgen receptor splice variants (PLOS, 2015) and PP2A as a viable treatment target in PTEN deficient prostate cancer cells (Scientific Reports, 2015). Novel treatment strategies are being evaluated in GEM and PDX models in efforts to overcome phenotypes of acquired resistance, metastasis and neuroendocrine differentiation and has led to the suggestion of treatment cycling to avoid resistance – a strategy currently in clinical trials at MSSM (Nature Reviews Clinical Oncology, 2016). Other major focus areas include understanding why clinical prostate cancers are poorly responsive to immune checkpoint inhibition. For this we have established transplant models of metastatic CRPC which are being used to investigate the effects of targeted T cell therapies (e.g. Jedi T cells with GFP specific TCR) and other strategies to target immunologically cold tumors. For MIBC, we are investigating the importance of lineage plasticity during progression and treatment exposure (Nature Communications, 2020, Accepted). Using carcinogen induced models of MIBC, we are determining the effects of lineage composition and plasticity on the immune cell landscape, infiltration and response to immune checkpoint therapies. These studies are important for understanding how to increase the response rates of clinical MIBCs to immune checkpoint blockade. Collectively, our research laboratory uses preclinical mouse modeling in a highly translational manner designed to identify and test new therapeutic strategies relevant to early phase clinical testing.
Our laboratory is affiliated with the Department of Oncological Sciences, the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai. You can find us in the Leon & Norma Hess Center for Science and Medicine