BioLab
University of Chicago, Park Laboratory
박준석 교수
연구실 소개
연구실 홈페이지Our research group primarily investigates the role of microbiome in modulating cancer immunity. We study mechanisms by which the gut microbes regulate the critical immune components in the Tumor Microenvironment (TME). By integrating gnotobiotic mouse models with expertise in fundamental immunology and leveraging the power of metabolomics, we aims to uncover the mechanisms by which commensal microbes and their metabolites modulate anti-tumor immunity, within the framework of cancer immunotherapy. We aim to 1) elucidate how gut microbes shape the immune landscape in the TME 2) identify gut microbial metabolites and signaling mediators of gut microbe-dependent anti-tumor immunity 3) determine the role of gut microbial immune modulation in regulating the response to immunotherapy. My research will provide critical insights into mechanisms by which the gut microbiota regulates anti-tumor immunity, and new therapeutic strategies for patients who do not respond to PD-1 pathway blockade. Ultimately, our goal is to develop novel and innovative therapeutic tools and strategies to enhance the effectiveness of cancer immunotherapies.
Joon Seok Park, Ph.D. (박준석)
Assistant Professor of Medicine, Biological Science Division, University of Chicago
EDUCATION
2016 Ph.D. in Immunology, Cornell University, Newyork, USA
2009 B.S. in Biochemistry, Yonsei University, Seoul, Korea
EXPERIENCE
2024 - present Assistant Professor, Medicine, Biological Science Division,University of Chicago, IL, USA
2017 - 2023 Postdoctoral Research Fellow, Dept. of Immunology, Harvard Medical School, MA USA
2016-2017 Postdoctoral Associate, Laboratory of Immune cell Epigenetics and Signaling, The Rockefeller University, NY, USA
연구분야
Commensal Microbe and Tumor Microenvironment
The tumor microenvironment (TME) is the ecosystem surrounding cancer cells. It consists of various innate and adaptive immune cells, cancer-associated fibroblasts, vascular cells, and nerves. Notably, the outcome of cancer immunotherapy is strongly associated with many immune-specific markers in the TME, regarding M1/M2 macrophages, dendritic cell subsets, CD8+ T cell to regulatory T cell ratio, and expression of co-stimulatory/co-inhibitory molecules. Previous reports including our publication and our preliminary data suggest that gut commensal microbes shape the immune landscape in the TME. However, how gut microbes regulate these cellular processes is not well-defined. 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.
Microbiome and Metabolites
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. As a member of the Cancer Metabolomics Center, we characterize and identify gut microbe-derived metabolites using metabolomic approaches. In collaboration with the Yao Lab at the University of Chicago (Yao, Park, 2023, Mol Cell; manuscript submitted), we also study the role of glycerol metabolism in regulating T cell-mediated immunity in the context of the microbiome. Our ultimate 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).
Gut-Tumor Axis
Our previous study showed that commensal microbes residing in the intestine significantly influence immune responses to distal tumors in the skin. An important question remains: How do the bacteria located in the gut impact the extra-intestinal immune landscape in the TME? How do changes in the intestinal immune system induced by microbes affect immune responses to tumors? Our preliminary data revealed that bacterial colonization could shape TCR repertoires in the colon and tumors. We hypothesize that certain gut microbes may modulate anti-tumor immunity and intestinal immune homeostasis by regulating cell trafficking. To prove this hypothesis, we are developing novel tools and approaches to track intestinal immune cells.
Approaches to modulate immunity using commensal microbes
Our previous study showed that targeting the ‘causal’ immune mechanisms by which gut microbes regulate anti-tumor immunity can be an effective strategy to improve immunotherapy, illustrating how we can utilize the microbiome for therapeutic purposes. Furthermore, our mechanistic studies can integrate with other approaches to innovate the use of the microbiome in therapy.
연구성과
최근 5년, 2020~
Peer-reviewed publications in the primary literature, exclusive of abstracts:
Lee, H.J.*, Park, J.S.*, Yoo, H.J., Lee, H.M., Lee, B.C., Kim, J.H. 2020. The Selenoprotein MsrB1 Instructs Dendritic Cells to Induce T-Helper 1 Immune Responses. Antioxidants (Basel) 9(10):1021.
Yao, C., Park, J.S., Kurmi, K., Hu, S., Notarangelo, G., Crowley, J., Jacobson, H., Hui, S., Sharpe, A.H., Haigis, M.C. 2023. Uncoupled glycerol-3-phosphate shuttle in kidney cancer reveals cytosolic GPD is essential to support lipid synthesis. Mol Cell 83(8):1340-1349.E7.
Park, J.S.*, Gazzaniga, F.S.*, Wu, M., Luthens, A., Gillis, J., Zheng, W., LaFleur, M.W., Johnson, S.B., Morad, G., Park, E.M., Zhou, Y., Watowich, S.S., Wargo, J.A., Freeman, G.J., Kasper, D.L., Sharpe, A.H. 2023. Nature 617(7960):377-385.
Kurmi, K., Liang, D., Van de Ven, R., Georgiev, P., Gassaway, B.M., Han, S.J., Notarangelo, G., Harris, Yao, C., Park, J.S., Hu, S.H., Peng, J., Drijvers, J.M., Boswell, S., Sokolov, A., Dougan, S.K., Sorger, P.K., Gygi, S.P., Sharpe, A.H., Haigis, M.C. 2023. Metabolic Modulation of Mitochondrial Mass during CD4+ T Cell Activation. Cell Chem Biol 30(9):1064-1075.E8.
Rowe, J.H., Elia, I., Shahid, O., Gaudiano, E.F., Sifnugel, N.E., Johnson, S., Reynolds, A.G., Fung, M.E., Joshi, S., LaFleur, M.W., Park, J.S., Pauken, K.E., Rabinowitz, J.D., Freeman, G.J., Haigis, M.C., Sharpe, A.H. 2023. Formate supplementation enhances anti-tumor CD8+ T cell fitness and efficacy of PD-1 blockade. Cancer Discov 2159-8290.
Georgiev, P.*, Han, S.J.*, Huang, A., Nguyen, T.H., Drijvers, J.M., Creasey, H., Pereira, J., Yao, C., Park, J.S., Conway, T., Fung, M.E., Liang, D., Peluso, M., Joshi, S., Rowe, J.H., Miller, B.C., Freeman, G.J., Sharpe, A.H., Haigis, M.C., Ringel, A.E. Age-associated contraction of tumor-specific T cells impairs anti-tumor immunity. Cancer Immunol Res CIR-24-0463.
Reviews, Commentaries, and Editorials:
Park, J.S., Gazzaniga, F.S., Kasper, D.L., Sharpe, A.H. 2023. Microbiota-dependent regulation of costimulatory and coinhibitory pathways via innate immune sensors and implications for immunotherapy. Exp Mol Med 55,1913-1921.
Peer-reviewed works in 'non-traditional' outlets:
Gazzaniga, F.S., Kasper, D.L., Park, J.S., Sharpe, A.H. US Patent 20220023359A1. Identification of Gut Bacteria that Promote an Anti-Tumor Response to Immunotherapy.
Gazzaniga, F.S., Park, J.S., Sharpe, A.H., Kasper, D.L. US Patent 20220213212A1. Methods and Compositions for Treating Cancer.
Freeman, G.J., Gazzaniga, F.S., Park, J.S., Sharpe, A.H., Kasper, D.L. US Patent 20230340124A1. Methods of Treating an Individual that has failed an Anti-PD-1/Anti-PD-L1 Therapy.
Sharpe, A.H., Kasper, D.L., Park, J.S., Gazzaniga, F.S., Freeman, G.J. PCT Patent WO2023150181A1. Methods and Compositions for Treating Cancer.
연구실 구성원
Are you interested in curing cancer by harnessing microbes and the power of our immune system?
Please, join us!
Homepage : https://parklab.uchicago.edu/
Contact : joonseokpark@uchicago.edu
The Park Lab is located on the 8th floor of the Knapp Center for Biomedical Discovery (KCBD) on the University of Chicago Hyde Park Campus. KCBD is the new glassy building depicted in the photo.
하고싶은 이야기
뉴욕과 보스턴이라는 동부의 학문 중심에 있으며 학교마다 학풍과 중점 연구가 다르다는 것을 알았습니다. 제가 시카고로 오게 된 이유는 물론 도시가 아름답고 살기 좋아서이기도 하지만 제가 연구하는 분야에서 선도적이기 때문입니다. 특히 시카고 대학교의 BSD (생명과학부) 와 Cancer Center 는 Microbiome, Cancer Metabolomics, Cancer Immunotherapy 를 중점 분야로 채택하고 있습니다. 전통적으로 면역학이 강했고, Microbiome 연구를 오랜기간 중점 투자를 하여 무균 동물실 등의 시설이 잘 갖춰져 있습니다. 그동안 하고 싶었지만 많은 제약에 부딪혀 실현하기 연구를 마음껏 할 수 있다는 점이 매력적으로 다가와서 시카고에서 커리어를 시작하게 되었습니다. 만약 Cancer Immunology, Microbiome, Metabolomics 의 융합 학문에 관심이 있으시면 협업이나 이곳에 오시는 것을 강력히 추천드립니다.
미국이라는 큰 무대에서 배우며 많은 순간 자신의 노력과 능력보다 누구를 만나느냐가 미래를 바꾼다는 것을 알았습니다. 이것은 비단 멘티로서뿐만 아니라 멘토의 입장에서도 마찬가지인 것 같습니다. 훌륭한 멘토들을 만나왔던 것처럼 훌륭한 멘티들을 만나게 되길 고대합니다. 함께 성장하며 트레이닝 기간을 넘어 인생의 사이언스 동반자가 되실 분을 만나고 싶습니다. 그리고 계속 배워야 하는 입장이지만 많은 좋은 멘토들 선배님들이 주신 배움을 저 또한 멘티들에게 전해주며 건강한 사이언스 커뮤니티를 만들게 되길 희망합니다.
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