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).
Harvard Medical School
Boston, MA
Instructor - Immunology and Microbiome
2024
Harvard Medical School
Boston, MA
Postdoctoral Fellowship - Immunology and Microbiome
2023
The Rockefeller University
New York, NY
Postdoctoral Associate - Immunology
2017
Cornell University
New York, NY
Ph.D. - Immunology
2016
Yonsei University
Seoul, Korea
B.S. - Biochemistry
2009
Age-Associated Contraction of Tumor-Specific T Cells Impairs Antitumor Immunity.
Age-Associated Contraction of Tumor-Specific T Cells Impairs Antitumor Immunity. Cancer Immunol Res. 2024 Nov 04; 12(11):1525-1541.
PMID: 39186561
Formate Supplementation Enhances Antitumor CD8+ T-cell Fitness and Efficacy of PD-1 Blockade.
Formate Supplementation Enhances Antitumor CD8+ T-cell Fitness and Efficacy of PD-1 Blockade. Cancer Discov. 2023 12 12; 13(12):2566-2583.
PMID: 37728660
Metabolic modulation of mitochondrial mass during CD4+ T cell activation.
Metabolic modulation of mitochondrial mass during CD4+ T cell activation. Cell Chem Biol. 2023 09 21; 30(9):1064-1075.e8.
PMID: 37716347
Microbiota-dependent regulation of costimulatory and coinhibitory pathways via innate immune sensors and implications for immunotherapy.
Microbiota-dependent regulation of costimulatory and coinhibitory pathways via innate immune sensors and implications for immunotherapy. Exp Mol Med. 2023 09; 55(9):1913-1921.
PMID: 37696895
Publisher Correction: Targeting PD-L2-RGMb overcomes microbiome-related immunotherapy resistance.
Publisher Correction: Targeting PD-L2-RGMb overcomes microbiome-related immunotherapy resistance. Nature. 2023 Jun; 618(7966):E27.
PMID: 37264079
Targeting PD-L2-RGMb overcomes microbiome-related immunotherapy resistance.
Targeting PD-L2-RGMb overcomes microbiome-related immunotherapy resistance. Nature. 2023 05; 617(7960):377-385.
PMID: 37138075
Uncoupled glycerol-3-phosphate shuttle in kidney cancer reveals that cytosolic GPD is essential to support lipid synthesis.
Uncoupled glycerol-3-phosphate shuttle in kidney cancer reveals that cytosolic GPD is essential to support lipid synthesis. Mol Cell. 2023 04 20; 83(8):1340-1349.e7.
PMID: 37084714
The Selenoprotein MsrB1 Instructs Dendritic Cells to Induce T-Helper 1 Immune Responses.
The Selenoprotein MsrB1 Instructs Dendritic Cells to Induce T-Helper 1 Immune Responses. Antioxidants (Basel). 2020 Oct 20; 9(10).
PMID: 33092166
Role of non-classical T cells in skin immunity.
Role of non-classical T cells in skin immunity. Mol Immunol. 2018 11; 103:286-292.
PMID: 30343117
Lipid-Reactive T Cells in Immunological Disorders of the Lung.
Lipid-Reactive T Cells in Immunological Disorders of the Lung. Front Immunol. 2018; 9:2205.
PMID: 30319649