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Joon Seok Park

TitleAssistant Professor
InstitutionUniversity of Chicago
DepartmentMedicine-Hematology and Oncology
AddressChicago IL 60637
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    Collapse Overview 
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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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    Collapse Biography 
    Collapse education and training
    Harvard Medical School, Boston, MAInstructor2024Immunology and Microbiome
    Harvard Medical School, Boston, MAPostdoctoral Fellowship2023Immunology and Microbiome
    The Rockefeller University, New York, NYPostdoctoral Associate2017Immunology
    Cornell University, New York, NYPh.D.2016Immunology
    Yonsei University, Seoul, KoreaB.S.2009Biochemistry

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    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    Newest   |   Oldest   |   Most Cited   |   Most Discussed   |   Timeline   |   Field Summary   |   Plain Text
    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Georgiev P, Han S, Huang AY, Nguyen TH, Drijvers JM, Creasey H, Pereira JA, Yao CH, Park JS, Conway TS, Fung ME, Liang D, Peluso M, Joshi S, Rowe JH, Miller BC, Freeman GJ, Sharpe AH, Haigis MC, Ringel AE. Age-associated contraction of tumor-specific T cells impairs antitumor immunity. Cancer Immunol Res. 2024 Aug 24. PMID: 39186561.
      Citations:    Fields:    
    2. Rowe JH, Elia I, Shahid O, Gaudiano EF, Sifnugel NE, Johnson S, Reynolds AG, Fung ME, Joshi S, LaFleur MW, Park JS, Pauken KE, Rabinowitz JD, Freeman GJ, Haigis MC, Sharpe AH. 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; PMCID: PMC10843486.
      Citations: 9     Fields:    Translation:HumansCells
    3. Kurmi K, Liang D, van de Ven R, Georgiev P, Gassaway BM, Han S, Notarangelo G, Harris IS, Yao CH, Park JS, Hu SH, Peng J, Drijvers JM, Boswell S, Sokolov A, Dougan SK, Sorger PK, Gygi SP, Sharpe AH, Haigis MC. Metabolic modulation of mitochondrial mass during CD4+ T cell activation. Cell Chem Biol. 2023 09 21; 30(9):1064-1075.e8. PMID: 37716347; PMCID: PMC10604707.
      Citations: 1     Fields:    Translation:AnimalsCells
    4. Park JS, Gazzaniga FS, Kasper DL, Sharpe AH. 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; PMCID: PMC10545783.
      Citations: 3     Fields:    
    5. Park JS, Gazzaniga FS, Wu M, Luthens AK, Gillis J, Zheng W, LaFleur MW, Johnson SB, Morad G, Park EM, Zhou Y, Watowich SS, Wargo JA, Freeman GJ, Kasper DL, Sharpe AH. Publisher Correction: Targeting PD-L2-RGMb overcomes microbiome-related immunotherapy resistance. Nature. 2023 Jun; 618(7966):E27. PMID: 37264079.
      Citations: 2     Fields:    
    6. Park JS, Gazzaniga FS, Wu M, Luthens AK, Gillis J, Zheng W, LaFleur MW, Johnson SB, Morad G, Park EM, Zhou Y, Watowich SS, Wargo JA, Freeman GJ, Kasper DL, Sharpe AH. Targeting PD-L2-RGMb overcomes microbiome-related immunotherapy resistance. Nature. 2023 05; 617(7960):377-385. PMID: 37138075; PMCID: PMC10219577.
      Citations: 39     Fields:    Translation:HumansAnimalsCells
    7. Yao CH, Park JS, Kurmi K, Hu SH, Notarangelo G, Crowley J, Jacobson H, Hui S, Sharpe AH, Haigis MC. 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; PMCID: PMC10131091.
      Citations: 5     Fields:    Translation:HumansCells
    8. Lee HJ, Park JS, Yoo HJ, Lee HM, Lee BC, Kim JH. The Selenoprotein MsrB1 Instructs Dendritic Cells to Induce T-Helper 1 Immune Responses. Antioxidants (Basel). 2020 Oct 20; 9(10). PMID: 33092166; PMCID: PMC7589095.
      Citations: 9     
    9. Park JS, Kim JH. Role of non-classical T cells in skin immunity. Mol Immunol. 2018 11; 103:286-292. PMID: 30343117.
      Citations: 2     Fields:    Translation:HumansAnimalsCells
    10. Ryu S, Park JS, Kim HY, Kim JH. Lipid-Reactive T Cells in Immunological Disorders of the Lung. Front Immunol. 2018; 9:2205. PMID: 30319649; PMCID: PMC6168663.
      Citations: 2     Fields:    Translation:HumansAnimalsCells
    11. Dobenecker MW, Park JS, Marcello J, McCabe MT, Gregory R, Knight SD, Rioja I, Bassil AK, Prinjha RK, Tarakhovsky A. Signaling function of PRC2 is essential for TCR-driven T cell responses. J Exp Med. 2018 04 02; 215(4):1101-1113. PMID: 29523590; PMCID: PMC5881460.
      Citations: 23     Fields:    Translation:AnimalsCells
    12. Park HJ, Park JS, Jeong YH, Son J, Ban YH, Lee BH, Chen L, Chang J, Chung DH, Choi I, Ha SJ. Correction: PD-1 Upregulated on Regulatory T Cells during Chronic Virus Infection Enhances the Suppression of CD8+ T Cell Immune Response via the Interaction with PD-L1 Expressed on CD8+ T Cells. J Immunol. 2015 Dec 15; 195(12):5841-2. PMID: 26637664.
      Citations: 9     Fields:    
    13. Park HJ, Park JS, Jeong YH, Son J, Ban YH, Lee BH, Chen L, Chang J, Chung DH, Choi I, Ha SJ. PD-1 upregulated on regulatory T cells during chronic virus infection enhances the suppression of CD8+ T cell immune response via the interaction with PD-L1 expressed on CD8+ T cells. J Immunol. 2015 Jun 15; 194(12):5801-11. PMID: 25934860.
      Citations: 108     Fields:    Translation:AnimalsCells
    14. Zamarin D, Holmgaard RB, Subudhi SK, Park JS, Mansour M, Palese P, Merghoub T, Wolchok JD, Allison JP. Localized oncolytic virotherapy overcomes systemic tumor resistance to immune checkpoint blockade immunotherapy. Sci Transl Med. 2014 Mar 05; 6(226):226ra32. PMID: 24598590; PMCID: PMC4106918.
      Citations: 380     Fields:    Translation:AnimalsCells
    15. Corse E, Gottschalk RA, Park JS, Sepulveda MA, Loke P, Sullivan TJ, Johnson LK, Allison JP. Cutting edge: chronic inflammatory liver disease in mice expressing a CD28-specific ligand. J Immunol. 2013 Jan 15; 190(2):526-30. PMID: 23248264; PMCID: PMC4964790.
      Citations: 2     Fields:    Translation:AnimalsCells
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