My research focuses on understanding the balance between protective antitumor immunity and immunotherapy toxicities. In preclinical mouse models my lab develops novel immunotherapies designed to reduce systemic toxicities. This has involved a variety of approaches, including concentrating therapeutic cytokines in the tumor microenvironment using single domain antibodies, as well as working with engineered proteins to improve therapeutic properties while reducing systemic toxicities.
In addition to immunotherapy mouse models, my lab uses complications of immunotherapy in patients to understand immune regulation in the gastrointestinal mucosa – gastrointestinal inflammatory toxicities are common after receiving treatment targeting the “checkpoint” receptors PD-1, PD-L1 or CTLA-4, indicating important roles for these receptors in regulating gut immune homeostasis. Using samples collected from the colons of patients who developed inflammation on immunotherapy, we are working to understand the cellular and molecular mechanisms that drive it. By understanding these mechanisms, we hope to understand how PD-1/PD-L1 and CTLA-4 maintain immune homeostasis in the gut, why this homeostasis breaks in some patients and not others, and identify novel treatment targets and markers of toxicity risk. This work may also provide insights into the early stages of autoimmunity, using immunotherapy as a well controlled human “model” of spontaneous human diseases such as ulcerative colitis and Crohn’s Disease.
55 Fruit St.
Massachusetts General Hospital
Boston, MA 02114