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keywords
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Immunology, Microbiome, Cancer Immunotherapy, Immunometabolism, T cell-mediated Immunity
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overview
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Dr. Park’s research group investigates how commensal microbes residing in the intestine influence systemic immunity, with a particular focus on cancer immunity. Recent studies, including those from Dr. Park’s lab, suggest that the gut microbiome plays a critical role in modulating responses to cancer immunotherapy. The lab is particularly interested in the signaling and metabolic mechanisms that mediate long-range communication between gut microbes and the immune system within the tumor microenvironment (TME).
To explore these mechanisms, Dr. Park’s team examines how gut microbes regulate key immune components within the TME, the complex ecosystem that surrounds cancer cells. Their publications and preliminary findings indicate that gut commensals significantly shape the immune landscape in tumors, although the precise molecular and cellular processes remain poorly understood. By integrating gnotobiotic mouse models with a strong foundation in fundamental immunology, Dr. Park’s lab aims to uncover how commensal microbes and their metabolites modulate anti-tumor immunity in the context of cancer immunotherapy.
One major direction of Dr. Park’s research focuses on dissecting the signaling pathways through which specific gut microbes influence immune cells in the TME. The lab aims to identify signaling receptors and mediators that translate microbial cues into changes in tumor-infiltrating immune cells, such as the PD-L2/RGMb modulation reported in their previous work. Additionally, the lab investigates how these pathways affect T cell responses and explores whether commensal-dependent immune mechanisms also play a role in other disease settings, such as chronic viral infections.
A second research direction explores how the gut microbiome shapes the metabolomic landscape of the TME. Commensal microbes produce a diverse array of immunomodulatory molecules, including surface structures and extracellular metabolites, that can influence the differentiation and function of immune cells. While bacterial metabolites are known to circulate systemically and regulate anti-tumor responses, their presence and function within the TME remain largely unexplored. Dr. Park’s group is working to fill this gap by examining microbial metabolites—particularly lipids and glycerol derivatives—and their immunological effects in tumors. Using metabolomic approaches, the lab identifies and characterizes these metabolites with the long-term goal of engineering bacteria to produce therapeutic molecules that enhance anti-tumor immunity. The team is also developing delivery strategies to target these bacterial products to the TME.
Together, Dr. Park’s research aims to deepen our understanding of the interplay between the gut microbiome and cancer immunity and to inform the development of innovative microbial-based therapies.
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Park, Joon Seok