Research

Ongoing projects include basic bench science, translational investigation, and working with native patient speciments. We interrogate the role of dendritic cells and T cells in barrier immunity and in tumor alike, including cross talk with other immune and non-immune populations.

• Why skin and skin cancer? As the primary barrier between the body and the outside world the skin functions as a unique immune organ, at the intersection of adaptive and innate immune responses. The importance of skin immunity is demonstrated through several lines of evidence.  First, successful vaccination strategies to cytolytic viruses rely on delivery of vaccine antigens to the skin- these including vaccinia skin scarification, and dermally-delivered influenza. Second, innate immune adjuvants that act on the cutaneous immune network (imiquimod, resiquimod) can lead to the regression of lentigo maligna and superficial spreading basal cell cancers. Third, steady state immune surveillance is critical to prevent skin cancers as evidenced by the markedly increased incidence of cutaneous neoplasias observed in renal transplant recipients maintained on immunosuppressive agents. 

• Skin cancer incidence outweighs all other cancers combined: We speculate this may be not only due to the high rate of barrier turnover present in the skin leading to increased rates of oncogenic mutations, but also due to local immune tolerance as a mechanism of preventing self-reactivity in tissue.

• Co-opting of tissue immune programing across cancers: Using a multidisciplinary approach including DC biology, tumor immunology, vaccine immunonology and functional genomics  our laboratory recently identified that tissue immune developmental signatures are co-opted across cancers of the tissue by shared conditioning cues. Through these programs we have identified novel immunotherapy target genes as well as new mechanisms of action for known targets.

• Cancer Vaccines: Despite the immune-responsive nature of skin cancers and the potential for skin resident immune cells to mediate vaccine responses, vaccines have not been generated to either prevent or treat skin cancers. Improved understanding of immune surveillance in the cutaneous microenvironment is needed. One focus of our program is to study Dendritic Cells (DC) in the cutaneous and local lymphoid environment- specialized cells which train T cells to respond to tumor and viral antigens. Our studies include identifying a role of DC in surveying skin and local lymphoid tissue as cancers arise, as well as finding ways to enhance DC function in ways that may be applied to cancer vaccines. Other projects study the molecular basis for T cell behavior in tissues and tumors alike, and the role of inhibitory molecules at shaping barrier surveillance.