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Immunology, Microbiome, Cancer Immunotherapy, Immunometabolism, T cell-mediated Immunity
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Our research group investigates how commensal microbes residing in the intestine influence systemic immunity, with a focus on cancer immunity. Recent studies, including our studies, suggest that the gut microbiome can regulate responses to cancer immunotherapy. We are interested in the signaling and metabolic elements that mediate the long-range communication between gut microbes and the immune system in tumors.
To understand this, we study the mechanisms by which gut microbes regulate critical immune components in the tumor microenvironment (TME), the ecosystem surrounding cancer cells. Our publications and preliminary data indicate that gut commensal microbes shape the immune landscape in the TME. However, how gut microbes regulate these cellular processes remains poorly defined. By integrating gnotobiotic mouse models with our expertise in fundamental immunology, we aim to uncover the mechanisms by which commensal microbes and their metabolites modulate anti-tumor immunity within the framework of cancer immunotherapy
The first direction of our studies is to dissect the signaling mechanisms by which specific gut microbes regulate immune cells in the TME. We aim to identify signaling receptors and mediators that link gut microbial signals to changes in tumor-infiltrating immune cells such as PD-L2/RGMb modulation that we have reported. Additionally, our lab is interested in the molecular and cellular mechanisms by which these signaling pathways modulate T cell responses. We will further examine whether the commensal-dependent immune mechanisms play an important role in other contexts, such as chronic viral infection.
The second direction of our research is to understand how the microbiome shapes the metabolomes of the tumor microenvironment (TME). Commensal microbes produce a multitude of immunomodulatory molecules, including bacterial surface compounds and extracellular metabolites. This diverse array of signaling molecules can alter the differentiation processes and functions of intestinal immune cells. Despite evidence of bacterial metabolites in the circulatory system and their involvement in regulating anti-tumor immunity, we have limited knowledge of bacterial metabolites and their derivatives in the TME. Addressing this knowledge gap will broaden our understanding of immune regulation by microbial components in the TME and potentially identify novel therapeutic agents produced by bacteria. Our research group examines gut microbial metabolites in tumors and determine their immunological roles in the TME. We first approach this project with a particular focus on lipids and glycerol, which previous publications and preliminary findings have identified as important in regulating immune cells and cancer cells. We characterize and identify gut microbe-derived metabolites using metabolomic approaches. Our goal is to engineer bacteria to produce desirable molecules that enhance anti-tumor immunity and to develop methods for delivering these molecules to the tumor microenvironment (TME).
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Park, Joon Seok