Pre-clinical Models of Prostate Cancer and Metastasis

Our experimental foundation relies on flexible, immunocompetent mouse models that enable precise genetic perturbation of cancer-associated alterations while preserving tumor microenvironment complexity. EvoCaP is a somatically engineered mouse model enabling flexible introduction of oncogenic alterations into prostate epithelial cells in immunocompetent mice. CRISPR-heritable barcodes track clonal dynamics throughout disease progression from primary to metastatic disease. We are actively expanding EvoCaP’s technological capabilities through multiplexing approaches for simultaneous multi-gene perturbation, tools to interrogate tumor microenvironment interactions, molecular recording systems to capture clonal transcriptional histories, and prime editing for precise genetic engineering. These advances enable us to model complex evolutionary trajectories and dissect the multifaceted determinants of metastatic expansion into specific organs.

Pre-clinical Models of Bladder Cancer and Metastasis 

Advanced bladder cancer models remain sparse, leaving critical gaps in our understanding of muscle-invasive bladder cancer (MIBC) evolution and metastatic progression. EvoCaB (Evolution in Cancer of the Bladder) addresses this need as a somatically engineered mouse model that enables direct perturbation of MIBC-associated genetic alterations in bladder urothelial cells. Using CRISPR-heritable barcodes, we monitor clonal dynamics throughout bladder cancer progression and track how different combinations of tumor suppressors drive disease evolution. Our current work characterizes genotypes enriched in metastatic lesions, providing insights into which alterations preferentially emerge during metastatic outgrowth. By systematically dissecting the genetic architecture of bladder cancer, EvoCaB provides the field with a much-needed experimental platform for discovering actionable vulnerabilities in this aggressive malignancy.