Investigators

Summary

My broad research program will address the following question: How can the microbiome-specific immune response be modified or targeted to improve cancer patient response to immunotherapy? I will utilize the expertise and tools I have developed throughout my training to track and modify tumor- and microbiota-specific T cells in hopes of identifying current immunotherapeutic hurdles and developing targeting strategies for these unique cell populations. In addition, I will assess how previous therapies or other external changes to the gut microbiome impact response to immunotherapy in both mouse models and patient samples. Ultimately, I will define the interplay between the immune responses to the ever-changing gut microbiome during tumorigenesis. These studies have the potential to not only improve our understanding of resistance to immunotherapy in cancer, but also to identify novel means of enhancing anti-tumor responses through modulation of the microbiota or its products.

My previous work as a Damon Runyon postdoctoral fellow in the Hand lab focused on the study of bacteria-specific CD4+ T cells in colorectal cancer (CRC) after microbiome modulation with a single bacteria, Helicobacter hepaticus (Hhep). We found that bacteria-specific CD4+ T cells were sufficient to drive anti-tumor immunity and lead to an increase in organized tertiary lymphoid structures and tumor immune infiltration. Interestingly, tumor clearance was dependent on CD4+ T cells but not CD8+ T cells, the latter of which is the primary target population for most immunotherapies. These observations were published in Immunity (2021) and suggested for the first time that CD4+ T cells that are specific to the microbiome directly support the anti-tumor immune response and may represent a new therapeutic target in tumors that occur at barrier surfaces such as CRC. In addition, I have recently found that modulation of the colon microbiome through colonization with Hhep can have beneficial impacts on tumors located in distant barrier sites as well, such as the skin. I have combined a number of innovative tools and techniques with tumor lines that contain controlled and tunable neoantigens to track tumor- and bacteria-specific immune responses. I believe that these models will provide tremendous and unique tools that will aid my overarching research program of study.