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Hongbo Chi, PhD
Hongbo Chi, PhD

Hongbo Chi, PhD

Member, St. Jude Faculty

  • Robert G. Webster Endowed Chair in Immunology

Departments

Education

PhD – University of Rochester, Rochester, NY

Research Interests

Immunometabolism and systems immunology

Metabolic reprogramming of cell fate: Our laboratory has a long-standing interest in understanding metabolic programs underlying immune cell fate. We have discovered the critical roles of glucose, lipid, amino acid and mitochondrial metabolism in cell fate choices between effector (e.g., Th17 and Tfh), regulatory and memory T cells or between type-1 and type-2 dendritic cells, as well as context (e.g., tissue or tumor microenvironment)-specific metabolic adaptation. See selected publications: Guo Nature 2023; Lim Nature 2021; Su Cell Metab 2020; Karmaus Nature 2019; Zeng Immunity 2016; Yang Immunity 2013; and Shi J Exp Med 2011; Chapman Immunity 2022 (review); and Lim Nature Chem Biol 2022 (review).

mTOR and nutrient signaling: Our laboratory has explored the regulation and function of nutrient signaling pathways in orchestrating T cell development, quiescence, quiescence exit and differentiation. Aside from mTOR signaling, we have also investigated other nutrient-related signaling pathways including LKB1, folliculin, Hippo and autophagy. See selected publications: Blanco Nature Cell Biol 2022; Long Nature 2021; Shi Immunity 2019; Yang Science Immunol 2018; Yang Nature 2017; Wei Nature Immunol 2016; Zeng Nature 2013; Chapman Nature Rev Immunol 2020 (review); and Chi Nature Rev Immunol 2012 (review).

In vivo CRISPR screens: We have extensively applied high-throughput CRISPR functional screens to discover novel drivers and targets or reconstruct causal networks to gain new biological insights. In particular, our in vivo functional genomics approaches have identified new targets to enable and improve T cell functions toward tumors and infections, some of which are being translated into next-generation CAR T cell therapies for pediatric cancer. See selected publications: Zhou Nature 2023; Guo Nature 2022; Fu Nature 2021; Huang Cell 2021; Wei Nature 2019; and Shi Nature Rev Immunol 2023 (review).

Multi-omics systems approaches to immunometabolism and disease: We have developed or applied multi-omics systems approaches in immunology and immuno-oncology, including multiplex proteomics, metabolomics, ATAC-seq, scRNA-seq and integrative network analyses (e.g., NetBID). These integrative systems tools are crucial to establish metabolic signaling circuits and immune-mediated mechanisms underlying cancer, autoimmunity and neurodegeneration, in an unbiased and systematic fashion that cannot be surmised from simpler or reductionist approach. See selected publications: Su Nature Immunol 2023; Du Nature 2018; Shi Immunity 2018; and Tan Immunity 2017.

Selected Publications

Zhou P, Shi H, Huang H, Sun X, Yuan S, Chapman NM, Connelly JP, Lim SA, Saravia J, Kc A, Pruett-Miller SM, Chi H. Single-cell CRISPR screens in vivo map T cell fate regulomes in cancer. Nature 624:154-163, 2023 (highlighted by Research Watch in Cancer Discov).

Guo C, You Z, Shi H, Sun Y, Du X, Palacios G, Guy C, Yuan S, Chapman NM, Lim SA, Sun X, Saravia J, Rankin S, Dhungana Y, Chi H. SLC38A2 and glutamine signalling in cDC1s dictate anti-tumour immunity. Nature 620:200-208, 2023 (highlighted by News and Views “cDC1 craves glutamine for its glory” in Nat Immunol, Spotlight “Glutamine availability unleashes dendritic cells' anti-tumor power” in Cell Chem Biol, and Research Watch in Cancer Discov).

Su W, Saravia J, Risch I, Rankin S, Guy C, Chapman NM, Shi H, Sun Y, KC A, Li W, Huang H, Lim SA, Hu H, Wang Y, Liu D, Jiao Y, Chen PC, Soliman H, Yan KK, Zhang J, Vogel P, Liu X, Serrano GE, Beach TG, Yu J, Peng J, Chi H. CXCR6 orchestrates brain CD8+ T cell residency and limits mouse Alzheimer’s disease pathology. Nat Immunol 24:1735-1747, 2023 (highlighted by News and Views “CD8+ T cells pump the brakes on Alzheimer’s disease” in Nat Immunol, Spotlight “Alzheimer’s defense: brain CD8+ T cells in action” in Trends Immunol, and Editors’ Choice “Restraining neuroinflammation in Alzheimer’s disease” in Sci Signal).

Fan H, Xia S, Xiang J, Li Y, Ross MO, Lim SA, Yang F, Tu J, Xie L, Dougherty U, Zhang FQ, Zheng Z, Zhang R, Wu R, Dong L, Su R, Chen X, Althaus T, Riedell PA, Jonker PB, Muir A, Lesinski GB, Rafiq S, Dhodapkar MV, Stock W, Odenike O, Patel AA, Opferman J, Tsuji T, Matsuzaki J, Shah H, Faubert B, Elf SE, Layden B, Bissonnette BM, He YY, Kline J, Mao H, Odunsi K, Gao X, Chi H*, He C*, Chen J*. Trans-vaccenic acid reprograms CD8+ T cells and anti-tumor immunity. Nature 623:1034-1043, 2023. (highlighted by Research Watch in Cancer Discov). * shared senior authorship.

Shi H, Doench JG, Chi H. CRISPR screens for functional interrogation of immunity. Nat Rev Immunol 23:363–380, 2023 (review).

You Z, Chi H. Lipid metabolism in dendritic cell biology. Immunol Rev 317:137-151, 2023 (review).

Guo C, Chi H. Immunometabolism of dendritic cells in health and disease. Adv Immunol 160:83-116, 2023 (review).

Guo A, Huang H, Zhu Z, Chen MJ, Shi H, Yuan S, Sharma P, Connelly JP, Liedmann S, Dhungana Y, Li Z, Haydar D, Yang M, Beere H, Yustein JT, DeRenzo C, Pruett-Miller SM, Crawford JC, Krenciute G, Roberts CWM, Chi H*, Green DR*. cBAF complex components and MYC cooperate early in CD8+ T cell fate. Nature 607:135-141, 2022. (highlighted by Research Watch in Cancer Discov). *Shared senior authorship.

Blanco DB, Chapman NM, Raynor JL, Xu C, Su W, KC A, Li W, Lim SA, Schattgen S, Shi H, Risch I, Sun Y, Dhungana Y, Kim Y, Wei J, Rankin S, Neale G, Thomas PG, Yang K*, Chi H*. Metabolic reprogramming of innate-like T cell fate and tissue homeostasis by PTEN. Nat Cell Biol 24:1642-1654, 2022 (highlighted by News and Views “PTEN checkMAITs type-17 innate-like T cells” in the same issue). *Shared senior authorship.

Chapman NM, Chi H. Metabolic adaptation of lymphocytes in immunity and disease. Immunity 55:14-30, 2022 (review).

Lim SA, Su W, Chapman NM, Chi H. Lipid metabolism in T cell signaling and function. Nat Chem Biol 18:470-481, 2022 (review).

Chi H. Immunometabolism at the intersection of metabolic signaling, cell fate, and systems immunology. Cell Mol Immunol 19:299-302, 2022 (editorial).

Long L, Wei J, Lim SA, Raynor JL, Shi H, Connelly JP, Wang H, Guy C, Xie B, Chapman NM, Fu G, Wang Y, Huang H, Su W, Saravia J, Risch I, Wang YD, Li Y, Niu M, Dhungana Y, KC A, Zhou P, Vogel P, Yu J, Pruett-Miller SM, Peng J, Chi H. CRISPR screens unveil signal hubs for nutrient licensing of T cell immunity. Nature 600:308-313, 2021.

Fu G, Guy CS, Chapman NM, Palacios G, Wei J, Zhou P, Long L, Wang YD, Qian C, Dhungana Y, Huang H, KC A, Shi H, Rankin S, Brown SA, Johnson A, Wakefield R, Robinson CG, Liu X, Sheyn A, Yu J, Jackowski S, Chi H. Metabolic control of TFH cells and humoral immunity by phosphatidylethanolamine. Nature 595:724-729, 2021.

Huang H, Zhou P, Wei J, Long L, Shi H, Dhungana Y, Chapman NM, Fu G, Saravia J, Raynor JL, Liu S, Palacios G, Wang YD, Qian C, Yu J, Chi H. In vivo CRISPR screening reveals nutrient signaling processes underpinning CD8+ T cell fate decisions. Cell 184:1245-1261, 2021. (highlighted by Preview “How to make a better T cell: in vivo CRISPR screens have some answers” in the same issue).

Lim SA, Wei J, Nguyen TM, Shi H, Su W, Palacios G, Dhungana Y, Chapman NM, Long L, Saravia J, Vogel P, Chi H. Lipid signalling enforces functional specialization of Treg cells in tumours. Nature 591:306-311, 2021. (highlighted by News and Views “Cancer aided by greasy traitors” in the same issue).

Raynor JL, Chapman NM, Chi H. Metabolic Control of Memory T-Cell Generation and Stemness. Cold Spring Harb Perspect Biol 13:a037770, 2021. (review)

Raynor JL, Chi H. Investigating the dynamic changes in iNKT cell metabolic profiles during development. Methods Mol Biol 2388:181-192, 2021. (review)

Wei J, Zheng W, Chapman NM, Geiger TL*, Chi H*. T cell metabolism in homeostasis and cancer immunity. Curr Opin Biotechnol 68:240-250, 2021. * Shared senior authorship. (review)

Shi H, Chi H. Polyamine: A metabolic compass for T helper cell fate direction. Cell 184:4109-4111, 2021. (preview)

Oh DY, Fong L, Newell EW, Turk MJ, Chi H, Chang HY, Satpathy AT, Fairfax B, Silva-Santos B, Lantz O. Toward a better understanding of T cells in cancer. Cancer Cell 39:1549-1552, 2021. (Voices)

Su W, Chapman NM, Wei J, Zeng H, Dhungana Y, Shi H, Saravia J, Zhou P, Long L, Rankin S, KC A, Vogel P, Chi H. Protein prenylation drives discrete signaling programs for the differentiation and maintenance of effector Treg cells. Cell Metab 32:996-1011, 2020.

Raynor JL, Liu C, Dhungana Y, Guy C, Chapman NM, Shi H, Neale G, Sesaki H, Chi H. Hippo/Mst signaling coordinates cellular quiescence with terminal maturation in iNKT cell development and fate decisions. J Exp Med 217:e20191157, 2020 (highlighted by Insights “Survivre et vivre: When iNKT cells met a Hippo” in the same issue).

Saravia J, Zeng H, Dhungana Y, Bastardo Blanco D, Nguyen TM, Chapman NM, Wang Y, Kanneganti A, Liu S, Raynor JL, Vogel P, Neale G, Carmeliet P, Chi H. Homeostasis and transitional activation of regulatory T cells require c-Myc. Sci Adv 6:eaaw6443, 2020.

Du X, Zeng H, Liu S, Guy C, Dhungana Y, Neale G, Bergo MO, Chi H. Mevalonate metabolism-dependent protein geranylgeranylation regulates thymocyte egress. J Exp Med 217:e20190969, 2020.

Chapman NM, Boothby MR, Chi H. Metabolic coordination of T cell quiescence and activation. Nat Rev Immunol 20:55-70, 2000. (review)

Saravia J, Raynor JL, Chapman NM, Lim SA, Chi H. Signaling networks in immunometabolism. Cell Res 30:328-342, 2020. (review)

Huang H, Long L, Zhou P, Chapman NM, Chi H. mTOR signaling at the crossroads of environmental signals and T-cell fate decisions. Immunol Rev 295:15-38, 2020. (review)

Wei J, Long L, Zheng W, Dhungana Y, Lim SA, Guy C, Wang Y, Wang YD, Qian C, Xu B, Kc A, Saravia J, Huang H, Yu J, Doench JG, Geiger TL, Chi H. Targeting REGNASE-1 programs long-lived effector T cells for cancer therapy. Nature 576:471–476, 2019. (highlighted by News and Views “Antitumour T cells stand the test of time” in the same issue)

Karmaus PWF, Chen X, Lim SA, Herrada AA, Nguyen TM, Xu B, Dhungana Y, Rankin S, Chen W, Rosencrance C, Yang K, Fan Y, Cheng Y, Easton J, Neale G, Vogel P, Chi H. Metabolic heterogeneity underlies reciprocal fates of TH17 cell stemness and plasticity. Nature 565:101-105, 2019. (highlighted by preview “mTOR Is Key to T Cell Transdifferentiation” in Cell Metab).

Shi H, Chapman NM, Wen J, Guy C, Long L, Dhungana Y, Rankin S, Pelletier S, Vogel P, Wang H, Peng J, Guan KL, Chi H. Amino Acids License Kinase mTORC1 Activity and Treg Cell Function via Small G Proteins Rag and Rheb. Immunity 51:1012-1027, 2019.

Wang Y, Du X, Wei J, Long L, Tan H, Guy C, Dhungana Y, Qian C, Neale G, Fu YX, Yu J, Peng J, Chi H. LKB1 orchestrates dendritic cell metabolic quiescence and anti-tumor immunity. Cell Res 29:391-405, 2019.

Saravia J, Chapman NM, Chi H. Helper T cell differentiation. Cell Mol Immunol 16:634-643, 2019. (review)

Shi H, Chi H. Metabolic Control of Treg Cell Stability, Plasticity, and Tissue-Specific Heterogeneity. Front Immunol 10:2716, 2019. (review)

Shi H, Liu C, Tan H, Li Y, Nguyen TL, Dhungana Y, Guy C, Vogel P, Neale G, Rankin S, Feng Y, Peng J, Tao W*, Chi H*. Hippo kinases Mst1/Mst2 sense and amplify IL-2R−STAT5 signaling in regulatory T cells to establish stable regulatory activity. Immunity 49:899-914, 2018. * Shared senior authorship.

Yang K, Blanco DB, Chen X, Dash P, Neale G, Rosencrance C, Easton J, Chen W, Dhungana Y, KC A, Awad W, Guo XZ, Thomas P, Chi H. Metabolic signaling directs the reciprocal lineage decisions of ab and gd T cells. Sci Immunol 3(25). pii: eaas9818, 2018. (cover story)

Du X, Wen J, Wang Y, Karmaus PWF, Khatamian A, Tan H, Li Y, Guy C, Nguyen TM, Dhungana Y, Neale G, Peng J, Yu J*, Chi H*. Hippo/Mst signalling couples metabolic state and immune function of CD8α+ dendritic cells. Nature 558:141-145, 2018. *Shared senior authorship.

Chapman NM, Zeng H, Nguyen TM, Wang Y, Vogel P, Dhungana Y, Liu X, Neale G, Locasale JW, Chi H. mTOR coordinates transcriptional programs and mitochondrial metabolism of activated Treg subsets to protect tissue homeostasis. Nat Commun 9:2095, 2018.

Zeng H, Yu M, Tan H, Li Y, Su W, Shi H, Dhungana Y, Guy C, Neale G, Cloer C, Peng J*, Wang D*, Chi H*. Discrete roles and bifurcation of PTEN signaling and mTORC1-mediated anabolic metabolism underlie IL-7-driven B lymphopoiesis. Sci Adv 4:eaar5701, 2018. *Shared senior authorship.

Show More

Yang K, Blanco DB, Neale G, Vogel P, Avila J, Clish CB, Wu C, Shrestha S, Rankin S, Long L, Kc A, Chi H. Homeostatic control of metabolic and functional fitness of Treg cells by LKB1 signalling. Nature 548:602-606, 2017. 

Karmaus PWF, Herrada AA, Guy C, Neale G, Dhungana Y, Long L, Vogel P, Avila J, Clish CB, Chi H. Critical roles of mTORC1 signaling and metabolic reprogramming for M-CSF-mediated myelopoiesis. J Exp Med 214:2629-2647, 2017.

Zeng H, Chi H. mTOR signaling in the differentiation and function of regulatory and effector T cells. Curr Opin Immunol 46:103-111, 2017. (review)

Wei J, Raynor J, Nguyen TL, Chi H. Nutrient and Metabolic Sensing in T Cell Responses. Front Immunol 8:247, 2017. (review)

Tan H, Yang K, Li Y, Shaw TI, Wang Y, Blanco DB, Wang X, Cho JH, Wang H, Rankin S, Guy C, Peng J*, Chi H*. Integrative Proteomics and Phosphoproteomics Profiling Reveals Dynamic Signaling Networks and Bioenergetics Pathways Underlying T Cell Activation. Immunity 46: 488-503, 2017. *Shared senior authorship.

Zeng H, Cohen S, Guy C, Shrestha S, Neale G, Brown SA, Cloer C, Kishton RJ, Gao X, Youngblood B, Do M, Li MO, Locasale JW, Rathmell JC*, Chi H*. mTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation. Immunity 45:540-554, 2016. *Shared senior authorship.

Wei J, Long L, Yang K, Guy C, Shrestha S, Chen Z, Wu C, Vogel P, Neale G, Green DR, Chi H. Autophagy enforces functional integrity of regulatory T cells by coupling environmental cues and metabolic homeostasis. Nat Immunol 17:277-285, 2016. (cover story)

Shi LZ, Saravia J, Zeng H, Kalupahana NS, Guy CS, Neale G, Chi H. Gfi1-Foxo1 axis controls the fidelity of effector gene expression and developmental maturation of thymocytes. Proc Natl Acad Sci USA 114:E67-E74, 2016.

Shrestha S, Yang K, Guy C, Vogel P, Neale G, Chi H. Treg cells require the phosphatase PTEN to restrain TH1 and TFH cell responses. Nat Immunol 16:178-187, 2015. (cover story)

Huang G, Wang Y, Vogel P, Chi H. Control of IL-17 receptor signaling and tissue inflammation by the p38a-MKP-1 signaling axis in a mouse model of multiple sclerosis. Sci Signal 8:ra24, 2015. (cover story) 

Zeng H, Chi H. Metabolic control of regulatory T cell development and function.Trends Immunol 36:3-12, 2015. (review).

Shrestha S, Yang K, Wei J, Karmaus PW, Neale G, Chi H. Tsc1 promotes the differentiation of memory CD8+ T cells via orchestrating the transcriptional and metabolic programs. Proc Natl Acad Sci USA 111:14858-14863, 2014.

Wei J, Yang K, Chi H. Cutting edge: Discrete functions of mTOR signaling in invariant NKT cell development and NKT17 fate decision. J Immunol 193:4297-4301, 2014.

Wu J, Yang J, Yang K, Wang H, Gorentla B, Shin J, Qiu Y, Que L, Foster WM, Xia Z, Chi H*, Zhong XP*. iNKT cells require TSC1 for terminal maturation and effector lineage fate decisions. J Clin Invest 124:1685-1698, 2014. *Shared senior authorship.

Zeng H, Yang K, Cloer C, Neale G, Vogel P, Chi H. mTORC1 couples immune signals and metabolic programming to establish Treg cell function. Nature 499: 485–490, 2013.

Yang K, Shrestha S, Zeng H, Karmaus PW, Neale G, Vogel P, Guertin DA, Lamb RF, Chi H. T cell exit from quiescence and differentiation into Th2 cells depend on Raptor-mTORC1-mediated metabolic reprogramming. Immunity 39:1043–1056, 2013.

Shi LZ, Kalupahana NS, Turnis ME, Neale G, Hock H, Vignali DA, Chi H. Inhibitory role of the transcription repressor Gfi1 in the generation of thymus-derive regulatory T cells. Proc Natl Acad Sci USA 110:E3198-3205, 2013.

Wang Y, Huang G, Zeng H, Yang K, Lamb RF, Chi H. Tuberous sclerosis 1 (Tsc1)-dependent metabolic checkpoint controls development of dendritic cells. Proc Natl Acad Sci USA 110:E4894-E4903, 2013.

Huang G, Wang Y, Chi H. Control of T cell fates and immune tolerance by p38α signaling in mucosal CD103+ dendritic cells. J Immunol 191:650-659, 2013.

Zeng H, Chi H. mTOR and lymphocyte metabolism. Cur Opin Immunol 25:347-355, 2013 (review).

Yang K, Chi H. mTOR and metabolic pathways in T cell quiescence and functional activation. Semin Immunol 24:421-428, 2013. (review)

Karmaus PW, Chi H. Genetic dissection of dendritic cell homeostasis and function: lessons from cell type-specific gene ablation. Cell Mol Life Sci Dec. 24, 2013. (review)

Huang G, Wang Y, Vogel P, Kanneganti TD, Otsu K, Chi H. Signaling via the kinase p38α programs dendritic cells to drive TH17 differentiation and autoimmune inflammation. Nat Immunol 13:152-161, 2012.

Wang Y, Huang G, Vogel P, Neale G, Reizis B, Chi H. Transforming growth factor beta-activated kinase 1 (TAK1)-dependent checkpoint in the survival of dendritic cells promotes immune homeostasis and function. Proc Natl Acad Sci USA 109: E343-E352, 2012.

Chi H. Regulation and function of mTOR signalling in T cell fate decisions. Nat Rev Immunol 12:325-338, 2012. (review)

Yang K, Neale G, Green DR, He W, Chi H. The tumor suppressor Tsc1 enforces quiescence of naïve T cells to promote immune homeostasis and function. Nat Immunol 12:888-897, 2011.

Huang G, Wang Y, Shi LZ, Kanneganti TD, Chi H. Signaling by the phosphatase MKP-1 in dendritic cells imprints distinct effector and regulatory T cell fates. Immunity 35:45-58, 2011.

Shi LZ, Wang R, Huang G, Vogel P, Neale G, Green DR*, Chi H*. HIF1α-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med 208:1367-1376, 2011. *Shared senior authorship.

Chi H. Sphingosine-1-phosphate and immune regulation: trafficking and beyond. Trends Pharmacol Sci 32:16-24, 2011. (review)

Liu G, Yang K, Burns S, Shrestha S, Chi H. The S1P1-mTOR axis directs the reciprocal differentiation of TH1 and Treg cells. Nat Immunol 11:1047-1056, 2010.

Liu G, Burns S, Huang G, Boyd K, Proia, RL, Flavell RA, Chi H. The receptor S1P1 overrides regulatory T cell-mediated immune suppression through Akt-mTOR. Nat Immunol 10:769-777, 2009.

Menon S*, Chi H*, Zhang H, Deng X, Flavell RA, Wei N. COP9 Signalosome subunit 8 (Csn8) is essential for peripheral T cell homeostasis and antigen receptor-induced cell cycle entry from quiescence. Nat Immunol 8:1236-1245, 2007. *Equal contribution.

Chi H, Barry SP, Roth RJ, Wu JJ, Jones EA, Bennett AM, Flavell RA. Dynamic regulation of pro- and anti-inflammatory cytokines by MAPK phosphatase 1 (MKP-1) in innate immune responses. Proc Natl Acad Sci USA 103:2274-2279, 2006.

Wan YY*, Chi H*, Xie M, Schneider MD, Flavell RA. The kinase TAK1 integrates antigen and cytokine receptor signaling for T cell development, survival and function. Nat Immunol 7:851-858, 2006. *Equal contribution.

Chi H, Flavell RA. Cutting edge: regulation of T cell trafficking and primary immune responses by sphingosine 1-phosphate receptor 1. J Immunol 174:2485-2488, 2005.

Chi H*, Sarkisian MR*, Rakic P, Flavell RA. Loss of mitogen-activated protein kinase kinase kinase 4 (MEKK4) results in enhanced apoptosis and defective neural tube development. Proc Natl Acad Sci USA 102:3846-3851, 2005. *Equal contribution.

Chi H, Lu B, Takekawa M, Davis RJ, Flavell RA. GADD45β/GADD45γ and MEKK4 comprise a genetic pathway mediating STAT4-independent IFNγ production in T cells. EMBO J 23:1576-1586, 2004.

Last update: December 2023

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