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Welcome to the Tobin Lab
Richard Tobin, PhD
Research Interests
The Tobin lab focuses on understanding the mechanisms that lead to effective antitumor immunity. The lab is specifically interested in the roles of unconventional T cells, the microbiome, and immunosuppressive cells in cancer patients.
Active Research Projects
Microbiome:MAIT Cell Axis in Melanoma Immunity
The microorganisms that normally inhabit the human gut, known as the microbiome, have recently been connected to successful treatment with immunotherapies. The objective of this project is to identify mechanisms of microbiome:immune cell crosstalk that can be modified to improve clinical outcomes for cancer patients. In this project we will determine whether mucosal-associated invariant T cells (MAITs), which recognize vitamin metabolite antigens produced by the microbiome, are one potential connection between the microbiome and responses to immunotherapies. We hypothesize that MAIT cells are required for anti- melanoma immunity and that activated MAIT cells link the microbiome and tumor immunity through microbial riboflavin synthesis. This hypothesis will be addressed in the following Specific Aims: (1) Determine the mechanism underlying the association between MAIT cells and the dynamics of riboflavin-synthesizing microbes in the gut microbiome during immune checkpoint inhibitor therapy; and (2) Define the contributions of MAIT cells to ICI therapy responses. Should this study reveal a role for MAIT cells in anti-tumor immunity that is dependent the microbiome, modalities aimed at expanding and/or activating MAIT cells during therapy may provide substantial clinical benefit for melanoma patients.
Unconventional T Cells in Melanoma Immunosurveillance
Cancer immunosurveillance, the process where the immune system recognizes and clears cells undergoing malignant transformation, is critical for cancer prevention. The mechanisms that govern the efficacy of cancer immunosurveillance remain to be fully elucidated and could lead to therapeutic interventions to prevent and treat cancers including melanoma. One unexplored potential mechanism is the recognition and elimination of melanoma cells by mucosal associated invariant T (MAIT) cells. This proposal’s objective is to determine the impact of MAIT cell immunosurveillance on melanoma development and the therapeutic potential of MAIT cell directed therapies to prevent and treat melanoma. We hypothesize that MAIT cells are critical elements in melanoma immunosurveillance by recognizing and eliminating melanocytes undergoing malignant transformation and that expanding MAIT cells will prevent melanoma development. Aim 1 will determine whether altered MAIT cell frequency or function is associated with cutaneous immunosurveillance and melanoma occurrence. Aim 2 will define the cellular and molecular contributions of MAIT cells to melanoma immunosurveillance.