Dissecting mechanisms of early tumorigenesis and niche-specific metastasis

While the genetic landscape of primary and metastatic cancers is now well understood, it remains unclear how early genetic events determine invasive capacity and metastasis of various cancers, including melanoma. It is also unknown why some tumors have a preference to metastasize to one organ over another. To delineate these fundamental questions, we apply single-cell genomics and imaging to defined genetic models of human and murine cancer precursors in tissue-engineered and pre-clinical in vivo models. Among metastatic niches, we are particularly interested in the brain as it is a major cause for morbidity and mortality across cancers.

Delineating resistance to immune checkpoint inhibitors in patient models

Immune checkpoint inhibitors (ICI) are exciting therapies that produce potentially durable responses in a portion of cancer patients, however, the vast majority of patients do not respond. We have previously identified a set of genes that are associated with drug resistance. We now use multi-scale genome-editing and single-cell genomics in patient-derived tumor/immune models to functionally to characterize putative drivers of resistance.

Development of tools to better understand mechanisms of T cell exclusion

T cell exclusion from the tumor microenvironment is one of the most important, yet poorly defined mechanisms of resistance to immune checkpoint inhibitors. We aim to develop new experimental and analytical tools to define drivers of T cell exclusion.