Zhiheng He

Tackling Gut Inflammation Through Immune Cell Research. Our lab is focused on uncovering how immune cells drive gut inflammation in two distinct yet related conditions:1. Inflammatory Bowel Diseases (IBD), chronic and relapsing conditions like Crohn’s disease and ulcerative colitis2. Immune Checkpoint Inhibitor (ICI)-Induced Colitis, a rising side effect of cancer immunotherapyAlthough these diseases have different origins, both result from overactive immune responses in the intestine. Our goal is to identify what makes certain immune cells harmful and how to stop them without impairing protective immunity or anti-tumor defense. We combine basic research (using mouse models, single-cell profiling, and CRISPR) with translational studies (including patient-derived samples and therapeutic testing) to develop more precise, effective treatments.

• Selective disruption of RORγt-CBFβ interaction by IMU-935 prevents RORγt-dependent Th17 autoimmunity but not thymocyte development. J Clin Invest. 2026 Jan 02; 136(1).. View in PubMed
• Decoding the mosaic of inflammatory bowel disease: Illuminating insights with single-cell RNA technology. Comput Struct Biotechnol J. 2024 Dec; 23:2911-2923.. View in PubMed
• Clinical drug screening reveals clofazimine potentiates the efficacy while reducing the toxicity of anti-PD-1 and CTLA-4 immunotherapy. Cancer Cell. 2024 May 13; 42(5):780-796.e6.. View in PubMed
• Distinct inflammatory Th17 subsets emerge in autoimmunity and infection. J Exp Med. 2023 10 02; 220(10).. View in PubMed
• Decoupling the role of RORγt in the differentiation and effector function of TH17 cells. Sci Adv. 2022 Oct 21; 8(42):eadc9221.. View in PubMed
• Correction: Oncogenic Herpesvirus KSHV Hijacks BMP-Smad1-Id Signaling to Promote Tumorigenesis. PLoS Pathog. 2022 Mar; 18(3):e1010390.. View in PubMed
• USP19 Suppresses Th17-Driven Pathogenesis in Autoimmunity. J Immunol. 2021 07 01; 207(1):23-33.. View in PubMed
• Correction: PRMT1 Plays a Critical Role in Th17 Differentiation by Regulating Reciprocal Recruitment of STAT3 and STAT5. J Immunol. 2019 Oct 01; 203(7):2021-2022.. View in PubMed
• SRC3 Is a Cofactor for RORγt in Th17 Differentiation but Not Thymocyte Development. J Immunol. 2019 02 01; 202(3):760-769.. View in PubMed
• Sumoylation of RORγt regulates TH17 differentiation and thymocyte development. Nat Commun. 2018 11 19; 9(1):4870.. View in PubMed
• PRMT1 Plays a Critical Role in Th17 Differentiation by Regulating Reciprocal Recruitment of STAT3 and STAT5. J Immunol. 2018 07 15; 201(2):440-450.. View in PubMed
• TCF-1 Inhibits IL-17 Gene Expression To Restrain Th17 Immunity in a Stage-Specific Manner. J Immunol. 2018 05 15; 200(10):3397-3406.. View in PubMed
• SRC1 promotes Th17 differentiation by overriding Foxp3 suppression to stimulate RORγt activity in a PKC-θ-dependent manner. Proc Natl Acad Sci U S A. 2018 01 16; 115(3):E458-E467.. View in PubMed
• A two-amino-acid substitution in the transcription factor RORγt disrupts its function in TH17 differentiation but not in thymocyte development. Nat Immunol. 2017 Oct; 18(10):1128-1138.. View in PubMed
• Regulation of Th17 Differentiation by IKKα-Dependent and -Independent Phosphorylation of RORγt. J Immunol. 2017 08 01; 199(3):955-964.. View in PubMed
• Fine-Tuning of the Kaposi’s Sarcoma-Associated Herpesvirus Life Cycle in Neighboring Cells through the RTA-JAG1-Notch Pathway. PLoS Pathog. 2016 Oct; 12(10):e1005900.. View in PubMed
• Ubiquitination of RORγt at Lysine 446 Limits Th17 Differentiation by Controlling Coactivator Recruitment. J Immunol. 2016 08 15; 197(4):1148-58.. View in PubMed
• Oncogenic herpesvirus KSHV Hijacks BMP-Smad1-Id signaling to promote tumorigenesis. PLoS Pathog. 2014 Jul; 10(7):e1004253.. View in PubMed
• Latency-associated nuclear antigen of Kaposi sarcoma-associated herpesvirus promotes angiogenesis through targeting notch signaling effector Hey1. Cancer Res. 2014 Apr 01; 74(7):2026-37.. View in PubMed
• NF-κB activation coordinated by IKKβ and IKKε enables latent infection of Kaposi’s sarcoma-associated herpesvirus. J Virol. 2014 Jan; 88(1):444-55.. View in PubMed
• Carboxyl-terminal amino acids 1052 to 1082 of the latency-associated nuclear antigen (LANA) interact with RBP-Jκ and are responsible for LANA-mediated RTA repression. J Virol. 2012 May; 86(9):4956-69.. View in PubMed
• A human herpesvirus miRNA attenuates interferon signaling and contributes to maintenance of viral latency by targeting IKKε. Cell Res. 2011 May; 21(5):793-806.. View in PubMed
• miR-K12-7-5p encoded by Kaposi’s sarcoma-associated herpesvirus stabilizes the latent state by targeting viral ORF50/RTA. PLoS One. 2011 Jan 20; 6(1):e16224.. View in PubMed
• Cellular corepressor TLE2 inhibits replication-and-transcription- activator-mediated transactivation and lytic reactivation of Kaposi’s sarcoma-associated herpesvirus. J Virol. 2010 Feb; 84(4):2047-62.. View in PubMed
• Inhibition of KSHV-infected primary effusion lymphomas in NOD/SCID mice by gamma-secretase inhibitor. Cancer Biol Ther. 2009 Nov; 8(22):2136-43.. View in PubMed

• Feng, Pinghui
• Chaudhary, Preet
• Wang, Rongfu