Zihai Li, MD, PhD
Leadership Title: Founding Director, Pelotonia Institute for Immuno-Oncology Klotz Chair in Cancer Research
Academic Title: Professor in the College of Medicine
Research Program: Translational Therapeutics
About Me
More info forI am a member of the Translational Therapeutics Program at the OSUCCC – James and the founding director of the Pelotonia Institute for Immuno-Oncology (PIIO), which is dedicated to transforming the OSUCCC – James into a leader in basic and clinical immunology research, including prevention and survivorship. I also hold the Klotz Chair in Cancer Research.
With primary interests in the mechanisms of immune regulation in cancer, my research team has made seminal contributions to understanding the immunological properties of heat shock proteins in cancer immunotherapy and immune tolerance. We provided the first genetic evidence linking the heat shock response to antigen cross-presentation and adaptive immunity; pioneered the use of autologous, tumor-derived HSP70-peptide complex for the immunotherapy of leukemia; and discovered that gp96, a paralog in the endoplasmic reticulum, is the master molecular chaperone for Toll-like receptors (TLRs).
I am internationally recognized as a leader in the field of gp96 biology due to a number of contributions such as the discovery of its ATPase activity, peptide-binding properties and client-binding domain. My current research interests focus on developing better immunotherapeutics against cancer by reprogramming the tolerogenic tumor microenvironment, including regulatory T-cells, thrombocytes and unfolded protein response. My work is supported by the National Institutes of Health, including a program project grant from the National Cancer Institute and four RO1s for which I am principal investigator.
I am also widely published in scientific journals on the topics of immune tolerance, cancer immunology and chaperone biology, and serve as an elected member of such professional organizations as the American Society for Clinical Investigation (ASCI) and the Association of American Physicians (AAP).
Academic Office & Contact Information
More info forAcademic Office:
Biomedical Research Tower
460 W 12th Ave
Columbus, Ohio 43210-2210Email:
Zihai.Li@osumc.eduVideos
More info forPublications
More info forOctober 4, 2024Inhibition of O-GlcNAc transferase activates type I interferon-dependent antitumor immunity by bridging cGAS-STING pathway.
Chen J, Zhao B, Dong H, Li T, Cheng X, Gong W, Wang J, Zhang J, Xin G, Yu Y, Lei YL, Black JD, Li Z, Wen H
Elife
August 29, 2024Graph Fourier transform for spatial omics representation and analyses of complex organs.
Chang Y, Liu J, Jiang Y, Ma A, Yeo YY, Guo Q, McNutt M, Krull JE, Rodig SJ, Barouch DH, Nolan GP, Xu D, Jiang S, Li Z, Liu B, Ma Q
Nat Commun
May 29, 2024GRP94 is an IGF-1R chaperone and regulates beta cell death in diabetes.
Kim DS, Song L, Gou W, Kim J, Liu B, Wei H, Muise-Helmericks RC, Li Z, Wang H
Cell Death Dis
May 23, 2024Spatial and functional targeting of intratumoral Tregs reverses CD8+ T cell exhaustion and promotes cancer immunotherapy.
Zhou L, Velegraki M, Wang Y, Mandula JK, Chang Y, Liu W, Song NJ, Kwon H, Xiao T, Bolyard C, Hong F, Xin G, Ma Q, Rubinstein MP, Wen H, Li Z
J Clin Invest
May 10, 2024DLL3-guided therapies in small-cell lung cancer: from antibody-drug conjugate to precision immunotherapy and radioimmunotherapy.
Su PL, Chakravarthy K, Furuya N, Brownstein J, Yu J, Long M, Carbone D, Li Z, He K
Mol Cancer
April 8, 2024Hallmarks of sex bias in immuno-oncology: mechanisms and therapeutic implications.
Xiao T, Lee J, Gauntner TD, Velegraki M, Lathia JD, Li Z
Nat Rev Cancer
March 23, 2024Post-infusion PD-1+CD8+CAR-T cells identify patients responsive to CD19-CAR-T therapy in non-Hodgkin's lymphoma.
Denlinger N, Song NJ, Zhang X, Jeon H, Peterson C, Wang Y, Reynolds K, Bolz R, Miao J, Song C, Wu D, Chan WK, Bezerra ED, Epperla N, Voorhees TJ, Brammer JE, Kittai AS, Bond DA, Sawalha Y, Sigmund AM, Reneau JC, Rubinstein MP, Hanel W, Christian B, Baiocchi RA, Maddocks KJ, Alinari L, Vasu S, de Lima M, Chung D, Jaglowski SM, Li Z, Huang X, Yang Y
Blood Adv
March 19, 2024Structural transitions modulate the chaperone activities of Grp94.
Amankwah YS, Fleifil Y, Unruh E, Collins P, Wang Y, Vitou K, Bates A, Obaseki I, Sugoor M, Alao JP, McCarrick RM, Gewirth DT, Sahu ID, Li Z, Lorigan GA, Kravats AN
Proc Natl Acad Sci U S A
February 13, 2024Targeting metabolic sensing switch GPR84 on macrophages for cancer immunotherapy.
Li J, Ma A, Zhang R, Chen Y, Bolyard C, Zhao B, Wang C, Pich T, Li W, Sun N, Ma Q, Wen H, Clinton SK, Carson WE, Li Z, Xin G
Cancer Immunol Immunother
February 10, 2024Roles of Androgen Receptor Signaling in Urothelial Carcinoma.
Sundi D, Collier KA, Yang Y, Diaz DA, Pohar KS, Singer EA, Gupta S, Carson WE, Clinton SK, Li Z, Messing EM
Cancers (Basel)
February 6, 2024Heat shock protein gp96 drives natural killer cell maturation and anti-tumor immunity by counteracting Trim28 to stabilize Eomes.
Xu Y, Li X, Cheng F, Zhao B, Fang M, Li Z, Meng S
Nat Commun
January 29, 2024Author Correction: Y chromosome loss in cancer drives growth by evasion of adaptive immunity.
Abdel-Hafiz HA, Schafer JM, Chen X, Xiao T, Gauntner TD, Li Z, Theodorescu D
Nature
January 12, 2024A Comprehensive Review of Immunotherapy Clinical Trials for Metastatic Urothelial Carcinoma: Immune Checkpoint Inhibitors Alone or in Combination, Novel Antibodies, Cellular Therapies, and Vaccines.
Patel DM, Mateen R, Qaddour N, Carrillo A, Verschraegen C, Yang Y, Li Z, Sundi D, Mortazavi A, Collier KA
Cancers (Basel)
January 6, 2024MarsGT: Multi-omics analysis for rare population inference using single-cell graph transformer.
Wang X, Duan M, Li J, Ma A, Xin G, Xu D, Li Z, Liu B, Ma Q
Nat Commun
January 4, 2024mRNA vaccines against SARS-CoV-2 induce divergent antigen-specific T-cell responses in patients with lung cancer.
Song NJ, Chakravarthy KB, Jeon H, Bolyard C, Reynolds K, Weller KP, Reisinger S, Wang Y, Li A, Jiang S, Ma Q, Barouch DH, Rubinstein MP, Shields PG, Oltz EM, Chung D, Li Z
J Immunother Cancer
December 22, 2023Emerging Immunotherapy Approaches for Advanced Clear Cell Renal Cell Carcinoma.
Meng L, Collier KA, Wang P, Li Z, Monk P, Mortazavi A, Hu Z, Spakowicz D, Zheng L, Yang Y
Cells
August 7, 2023Asparagine restriction enhances CD8+ T cell metabolic fitness and antitumoral functionality through an NRF2-dependent stress response.
Gnanaprakasam JNR, Kushwaha B, Liu L, Chen X, Kang S, Wang T, Cassel TA, Adams CM, Higashi RM, Scott DA, Xin G, Li Z, Yang J, Lane AN, Fan TW, Zhang J, Wang R
Nat Metab
July 1, 2023Y chromosome loss in cancer drives growth by evasion of adaptive immunity.
Abdel-Hafiz HA, Schafer JM, Chen X, Xiao T, Gauntner TD, Li Z, Theodorescu D
Nature
June 16, 2023CD200R signaling contributes to unfavorable tumor microenvironment through regulating production of chemokines by tumor-associated myeloid cells.
Lin CH, Talebian F, Yang L, Zhu J, Liu JQ, Zhao B, Basu S, Pan X, Chen X, Yan P, Carson WE, Xin G, Wen H, Wang R, Li Z, Ma Q, Bai XF
iScience
May 26, 2023A Pilot Cross-Sectional Study of Immunological and Microbiome Profiling Reveals Distinct Inflammatory Profiles for Smokers, Electronic Cigarette Users, and Never-Smokers.
Shields PG, Ying KL, Brasky TM, Freudenheim JL, Li Z, McElroy JP, Reisinger SA, Song MA, Weng DY, Wewers MD, Whiteman NB, Yang Y, Mathé EA
Microorganisms
May 18, 2023Cellular gp96 upregulates AFP expression by blockade of NR5A2 SUMOylation and ubiquitination in HCC.
Qian L, Liang Z, Wang Z, Wang J, Li X, Zhao J, Li Z, Chen L, Liu Y, Ju Y, Li C, Meng S
J Mol Cell Biol
September 1, 2022Selective targeting of GARP-LTGFβ axis in the tumor microenvironment augments PD-1 blockade via enhancing CD8+ T cell antitumor immunity.
Li A, Chang Y, Song NJ, Wu X, Chung D, Riesenberg BP, Velegraki M, Giuliani GD, Das K, Okimoto T, Kwon H, Chakravarthy KB, Bolyard C, Wang Y, He K, Gatti-Mays M, Das J, Yang Y, Gewirth DT, Ma Q, Carbone D, Li Z
J Immunother Cancer
August 19, 2022Sex-biased adaptive immune regulation in cancer development and therapy.
Schafer JM, Xiao T, Kwon H, Collier K, Chang Y, Abdel-Hafiz H, Bolyard C, Chung D, Yang Y, Sundi D, Ma Q, Theodorescu D, Li X, Li Z
iScience
July 27, 2022A bayesian multivariate mixture model for high throughput spatial transcriptomics.
Allen C, Chang Y, Neelon B, Chang W, Kim HJ, Li Z, Ma Q, Chung D
Biometrics
June 11, 2022Translational landscape of glioblastoma immunotherapy for physicians: guiding clinical practice with basic scientific evidence.
Kreatsoulas D, Bolyard C, Wu BX, Cam H, Giglio P, Li Z
J Hematol Oncol
May 18, 2022The role of biomarkers in personalized immunotherapy.
Sankar K, Ye JC, Li Z, Zheng L, Song W, Hu-Lieskovan S
Biomark Res
May 2, 2022Converting Tumoral PD-L1 into a 4-1BB Agonist for Safer and More Effective Cancer Immunotherapy.
Li Z, Azar JH, Rubinstein MP
Cancer Discov
April 14, 2022Androgen conspires with the CD8+ T cell exhaustion program and contributes to sex bias in cancer.
Kwon H, Schafer JM, Song NJ, Kaneko S, Li A, Xiao T, Ma A, Allen C, Das K, Zhou L, Riesenberg B, Chang Y, Weltge P, Velegraki M, Oh DY, Fong L, Ma Q, Sundi D, Chung D, Li X, Li Z
Sci Immunol
April 13, 2022IL-27 Induces CCL5 Production by T Lymphocytes, Which Contributes to Antitumor Activity.
Hu A, Zhu J, Zeng C, Lin CH, Yu J, Liu JQ, Lynch K, Talebian F, Pan X, Yan J, Dong Y, Li Z, Bai XF
Journal of Immunology
April 4, 2022Sex differences in bladder cancer: emerging data and call to action.
Theodorescu D, Li Z, Li X
Nat Rev Urol
March 18, 2022Transforming growth factor-β1 in regulatory T cell biology.
Moreau JM, Velegraki M, Bolyard C, Rosenblum MD, Li Z
Sci Immunol
March 11, 2022Efficacy and safety of CD24Fc in hospitalised patients with COVID-19: a randomised, double-blind, placebo-controlled, phase 3 study.
Welker J, Pulido JD, Catanzaro AT, Malvestutto CD, Li Z, Cohen JB, Whitman ED, Byrne D, Giddings OK, Lake JE, Chua JV, Li E, Chen J, Zhou X, He K, Gates D, Kaur A, Chen J, Chou HY, Devenport M, Touomou R, Kottilil S, Liu Y, Zheng P, SAC-COVID Study Team
Lancet Infect Dis
January 10, 2022Treatment with soluble CD24 attenuates COVID-19-associated systemic immunopathology.
Song NJ, Allen C, Vilgelm AE, Riesenberg BP, Weller KP, Reynolds K, Chakravarthy KB, Kumar A, Khatiwada A, Sun Z, Ma A, Chang Y, Yusuf M, Li A, Zeng C, Evans JP, Bucci D, Gunasena M, Xu M, Liyanage NPM, Bolyard C, Velegraki M, Liu SL, Ma Q, Devenport M, Liu Y, Zheng P, Malvestutto CD, Chung D, Li Z
J Hematol Oncol
January 5, 2022CNPY2 Contributes to Liver Oncogenesis by Promoting UPR-dependent destabilization of p53.
Hong F, Lin CY, Yan J, Dong Y, Ouyang Y, Kim D, Zhang X, Liu B, Sun S, Gu W, Li Z
Hepatology
January 1, 2022Concomitant Medication Effects on Immune Checkpoint Inhibitor Efficacy and Toxicity.
Sieber B, Strauss J, Li Z, Gatti-Mays ME
Front Oncol
January 1, 2022Define and visualize pathological architectures of human tissues from spatially resolved transcriptomics using deep learning.
Chang Y, He F, Wang J, Chen S, Li J, Liu J, Yu Y, Su L, Ma A, Allen C, Lin Y, Sun S, Liu B, Javier Otero J, Chung D, Fu H, Li Z, Xu D, Ma Q
Comput Struct Biotechnol J
January 1, 2022Mechanism of Sex Differences in Bladder Cancer: Evident and Elusive Sex-biasing Factors.
Lam CM, Li Z, Theodorescu D, Li X
Adv Psychosom Med
December 30, 2021COVID-19 mRNA booster vaccines elicit strong protection against SARS-CoV-2 Omicron variant in patients with cancer.
Zeng C, Evans JP, Chakravarthy K, Qu P, Reisinger S, Song NJ, Rubinstein MP, Shields PG, Li Z, Liu SL
Cancer Cell
November 21, 2021Impaired neutralizing antibody response to COVID-19 mRNA vaccines in cancer patients.
Zeng C, Evans JP, Reisinger S, Woyach J, Liscynesky C, Boghdadly ZE, Rubinstein MP, Chakravarthy K, Saif L, Oltz EM, Gumina RJ, Shields PG, Li Z, Liu SL
Cell Biosci
October 29, 2021Pancreatic cancer cells render tumor-associated macrophages metabolically reprogrammed by a GARP and DNA methylation-mediated mechanism.
Zhang M, Pan X, Fujiwara K, Jurcak N, Muth S, Zhou J, Xiao Q, Li A, Che X, Li Z, Zheng L
Signal Transduct Target Ther
October 7, 2021Immune checkpoint inhibitor-related thrombocytopenia: incidence, risk factors and effect on survival.
Haddad TC, Zhao S, Li M, Patel SH, Johns A, Grogan M, Lopez G, Miah A, Wei L, Tinoco G, Riesenberg B, Li Z, Meara A, Bertino EM, Kendra K, Otterson G, Presley CJ, Owen DH
Cancer Immunol Immunother
September 27, 2021Combination strategies to maximize the benefits of cancer immunotherapy.
Zhu S, Zhang T, Zheng L, Liu H, Song W, Liu D, Li Z, Pan CX
J Hematol Oncol
July 31, 2021Novel strategies for immuno-oncology breakthroughs with cell therapy.
Liu H, Pan C, Song W, Liu D, Li Z, Zheng L
Biomark Res
July 20, 2021Type-2 dendritic cells mediate control of cytotoxic T cell-resistant tumors.
Iwanowycz S, Ngoi S, Li Y, Hill M, Koivisto C, Parrish M, Guo B, Li Z, Liu B
JCI Insight
July 1, 2021Myeloid Endoplasmic Reticulum Resident Chaperone GP96 Facilitates Inflammation and Steatosis in Alcohol-Associated Liver Disease.
Ratna A, Lim A, Li Z, Argemi J, Bataller R, Chiosis G, Mandrekar P
Hepatol Commun
April 3, 2021Pharmacological Regulation of Tumor Hypoxia in Model Murine Tumors and Spontaneous Canine Tumors.
Benej M, Wu J, Kreamer M, Kery M, Corrales-Guerrero S, Papandreou I, Williams TM, Li Z, Graves EE, Selmic LE, Denko NC
Cancers (Basel)
March 22, 2021Hedgehog-induced PD-L1 on tumor-associated macrophages is critical for suppression of tumor-infiltrating CD8+ T cell function.
Petty AJ, Dai R, Lapalombella R, Baiocchi RA, Benson DM, Li Z, Huang X, Yang Y
JCI Insight
March 9, 2021Autocrine transforming growth factor β1 in regulatory T cell biology-gone but not missed.
Velegraki M, Salem M, Ansa-Addo EA, Wu BX, Li Z
Immunity
February 17, 2021IRIS-FGM: an integrative single-cell RNA-Seq interpretation system for functional gene module analysis.
Chang Y, Allen C, Wan C, Chung D, Zhang C, Li Z, Ma Q
Bioinformatics
January 1, 2021Targeting Metabolic Pathways of Myeloid Cells Improves Cancer Immunotherapy.
Li J, Bolyard C, Xin G, Li Z
Front Cell Dev Biol
July 28, 2020Extracellular gp96 is a crucial mediator for driving immune hyperactivation and liver damage.
Guan Z, Ding Y, Liu Y, Zhang Y, Zhao J, Li C, Li Z, Meng S
Sci Rep
June 23, 2020Summary of the 2019 BMT CTN Myeloma Intergroup Workshop on Minimal Residual Disease and Immune Profiling.
Holstein SA, Howard A, Avigan D, Bhutani M, Cohen AD, Costa LJ, Dhodapkar MV, Gay F, Gormley N, Green DJ, Hillengass J, Korde N, Li Z, Mailankody S, Neri P, Parekh S, Pasquini MC, Puig N, Roodman GD, Samur MK, Shah N, Shah UA, Shi Q, Spencer A, Suman VJ, Usmani SZ, McCarthy PL
Biol Blood Marrow Transplant
June 19, 2020IL-6 fuels durable memory for Th17 cell-mediated responses to tumors.
Knochelmann HM, Dwyer CJ, Smith AS, Bowers JS, Wyatt MM, Nelson MH, Rangel Rivera GO, Horton JD, Krieg C, Armeson K, Lesinski GB, Rubinstein MP, Li Z, Paulos CM
Cancer Res
June 7, 2020Platelet and hemoglobin count at diagnosis are associated with survival in African American and Caucasian patients with colorectal cancer.
Wallace K, Li H, Brazeal JG, Lewin DN, Sun S, Ba A, Paulos CM, Rachidi S, Li Z, Alekseyenko AV
Cancer Epidemiol
May 1, 2020RNA binding protein PCBP1 is an intracellular immune checkpoint for shaping T cell responses in cancer immunity.
Ansa-Addo EA, Huang HC, Riesenberg B, Iamsawat S, Borucki D, Nelson MH, Nam JH, Chung D, Paulos CM, Liu B, Yu XZ, Philpott C, Howe PH, Li Z
Sci Adv
May 1, 2020RNA binding protein PCBP1 is an intracellular immune checkpoint for shaping T cell responses in cancer immunity.
Ansa-Addo EA, Huang HC, Riesenberg B, Iamsawat S, Borucki D, Nelson MH, Nam JH, Chung D, Paulos CM, Liu B, Yu XZ, Philpott C, Howe PH, Li Z
Sci Adv