About

Zhiheng He is an Assistant Professor of Immunology and Immune Therapeutics at the Keck School of Medicine of USC. His research focuses on tackling gut inflammation by investigating how immune cells drive conditions such as Inflammatory Bowel Diseases (IBD), including Crohn’s disease and ulcerative colitis, as well as immune checkpoint inhibitor (ICI)-induced colitis, a side effect of cancer immunotherapy. His lab aims to identify the factors that make certain immune cells harmful and to develop strategies to inhibit their damaging effects without impairing protective immunity or anti-tumor responses. His work combines basic research methods, including mouse models, single-cell profiling, and CRISPR technology, with translational studies involving patient-derived samples and therapeutic testing. His contributions include elucidating mechanisms of intestinal inflammation, exploring immune cell subsets, and testing potential treatments to improve outcomes for patients suffering from these inflammatory conditions.

Research topics

• Biology
• Genetics
• Materials science
• Nanotechnology
• Computational biology
• Evolutionary biology
• Medicine
• Chromatography
• Internal medicine
• Chemistry
• Cell biology
• Cancer research
• Oncology

Selected publications

• Multi‐Machine Learning Elucidates Clinical Potential of Epithelial‐Mesenchymal Transition‐Associated Long Non‐Coding RNAs in Breast Cancer Progression

  Biotechnology Journal · 2026-04-01

  article

  Breast carcinoma (BRCA) involves multiple molecular markers, including epithelial-mesenchymal transition (EMT), which induce cell migration. However, the specific impact of long non-coding RNAs (lncRNAs) on EMT in BRCA remains uncertain. In this study, a prognostic model was constructed using EMT-associated lncRNAs (EALs), with utilization of integrative machine learning algorithms. The optimal model consisted of 15 EALs, with an AUC of 0.89 at 5 years, showing its potential as a plausible biomarker for BRCA. Among high-risk individuals, a significant increase in pathways linked to the preservation of equilibrium and immune defense was observed. Moreover, it was indicated that immunotherapy elicited negative responses in this group. Somatic mutations displayed higher TP53 rates in high-risk patients and increased CDH1/PIK3CA in low-risk ones. Notably, AC055854.1 and MIR205HG, important EALs in the model, probably regulate BRCA development through the lncRNA-microRNA-mRNA axis. Spatial transcriptome analysis revealed higher expression levels of EALs and high-risk related genes in ductal carcinoma in situ (DCIS), invasive mixed ductal/lobular carcinoma (IDC), and triple-negative BRCA (TNBC) than in breast metastasis (BMS) samples. And neutrophils were exclusively observed within the tumor microenvironment (TME) of BMS. All these findings emphasized EALs' value in revolutionizing clinical decision-making for personalized treatment strategies in BRCA cases.

  PublisherDOI

• Spatiotemporal Evolution of Malignant Hepatocyte Clones Unveils Immune Evasion Features and Therapeutic Vulnerabilities in Hepatocellular Carcinoma

  Biotechnology Journal · 2026-01-01 · 1 citations

  article

  ABSTRACT Hepatocellular carcinoma (HCC), a highly lethal disease often developing in the context of chronic liver disease, is marked by high relapse rates and low 5‐year survival. To investigate the multicellular ecosystem and molecular features of hepatocarcinogenesis and progression, a comprehensive analysis integrating single‐cell and spatial transcriptomics was conducted. Significant alterations were observed in various cell types, notably an increase in liver parenchymal and endothelial cells, which play critical roles in tissue repair and angiogenesis. Scissor + cells, predominantly hepatocytes, were identified as potentially evolving into malignant cells with poor prognosis and enhanced immune evasion capabilities. Key genes associated with Scissor + cells exhibited potential as cancer prognostic markers. Additionally, the disruption of cellular communication networks during malignant progression revealed the evolution of hepatocytes into cancerous phenotypes. The enhanced signaling pathways, such as MDK‐SDC4 and COL4A‐SDC, were identified as pivotal in driving the malignant transformation of hepatocytes. This transformative process, wherein Scissor + cells acquire malignant features, highlights novel mechanisms of cancer progression. These findings provide deeper insights into hepatocarcinogenesis and offer potential avenues for targeted and personalized therapeutic strategies.

  PublisherDOI

• Two-Step Electrochemical Oxidation Enables Synergistic Fe³⁺ Doping and PO₄³⁻ Modification of Nickel-Based Catalysts for Efficient Oxygen Evolution

  Chemical Communications · 2026-01-01

  article1st authorCorresponding

  A two-step electrochemical oxidation strategy is developed to fabricate (Fe³⁺,PO₄³⁻)-Ni(OH)₂/NiOOH catalyst on a commercial nickel mesh with the optimal ratio of 0.1 mmol/L Fe³⁺ and 5 mmol/L PO₄³⁻ for alkaline...

  PublisherDOI

• Corrigendum to “Comprehensive non-small cell lung cancer targets: From computational prediction to clinical breakthroughs in overcoming drug resistance” [Biochem. Pharmacol. 242(Part 2) (2025) 117333]

  Biochemical Pharmacology · 2026-02-13

  article
  PublisherDOI

• Quantifying cognitive workload in ICU nursing: a computational modeling approach to ECMO circuit priming

  Cognition Technology & Work · 2026-03-30

  article
  PublisherDOI

• <div> Online Appendix for Expected Return in Night and Day: </div><div> The Role of Trading Volume</div>

  SSRN Electronic Journal · 2026-01-01

  preprintOpen accessSenior author
  PublisherDOI

• DAB2IP modulates intestinal inflammation by enhancing ILC3 function in the gut

  The Journal of Immunology · 2026-04-01

  articleSenior author

  Group 3 innate lymphoid cells (ILC3s) preserve intestinal barrier integrity by producing IL-22 and IL-17A, yet the molecular mechanisms that maintain these cytokines during inflammation are incompletely defined. Here, we identify DAB2IP as a cell-intrinsic regulator of ILC3 effector function. In human inflammatory bowel disease mucosa, DAB2IP expression is reduced and associated with transcriptional programs linked to impaired epithelial repair. In murine models, inflammatory cues dynamically modulate Dab2ip in ILC3s, and genetic loss of DAB2IP diminishes IL-22 and IL-17A, compromising host defense during Citrobacter rodentium infection, and exacerbates dextran sulfate sodium-induced colitis. Mechanistically, DAB2IP enables efficient NF-κB activation, promoting IκBα degradation, p65 nuclear accumulation, and thus transcription of Il22/Il17a and NF-κB targets. These results reveal a context-dependent role for DAB2IP as a positive regulator of NF-κB in ILC3s, highlighting its previously unknown function in mucosal immunity and epithelial repair, and suggesting that restoring DAB2IP signaling could enhance barrier protection during intestinal inflammation.

  PublisherDOI

• Enhanced HIF-1α cooperation by a human RORγt mutant potentiates Th17 pathogenicity

  Cell Reports · 2026-03-17

  articleOpen accessSenior author

  <h2>Summary</h2> T helper 17 (Th17) cells are pivotal in mucosal defense and autoimmune pathology, with their function governed by the transcription factor retinoic acid receptor-related orphan receptor gamma t (RORγt). Although genome-wide association studies link <i>RORC</i> variants to inflammatory diseases, their functional consequences remain poorly understood. We identify a pathogenic RORγt mutation N277D (mouse homolog N275D) that amplifies Th17 pathogenicity through cooperation with hypoxia-inducible factor HIF-1α. This mutation enhances IFN-γ and other Th1-type cytokine production by Th17 cells, exacerbating colitis without disrupting T cell development or homeostasis. Integrated transcriptomic and metabolomic profiling reveals activation of glycolytic and hypoxia-associated pathways, consistent with increased RORγt^N275D recruitment by HIF-1α to the <i>Pdk1</i> locus. Notably, silencing <i>Pdk1</i> normalizes the excessive IFN-γ production in RORγt^N275D Th17 cells. Together, these findings define a regulatory axis linking RORγt and HIF-1α that coordinates transcriptional and metabolic programs in pathogenic Th17 cells, providing a framework for dissecting the functional impact of autoimmune risk variants.

  PublisherOA PDFDOI

• ALDH2 inhibition induces synthetic lethality in APC-deficient colorectal cancer via ROS/ASK1/JNK pathway

  Genes & Diseases · 2026-01-01

  articleOpen access
  PublisherDOI

• SAT-147 The Effect of Glucagon-Like Peptide-1 Receptor Agonists on Erectile Dysfunction and Testosterone Levels: A Systematic Review and Meta-Analysis

  Journal of the Endocrine Society · 2025-10-01

  reviewOpen accessSenior author

  Abstract Disclosure: A. Ezici: None. S. Ramadan: None. A. Bardak: None. Z. He: None. Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for type 2 diabetes mellitus (T2DM) and obesity, but their impact on male reproductive health remains unclear. Previous studies have reported conflicting effects on erectile dysfunction (ED) and testosterone levels, ranging from potential improvements to no benefit or even adverse effects. Given the rising prevalence of T2DM, obesity, and sexual dysfunction, as well as the growing use of GLP-1RAs, we conducted this meta-analysis to evaluate their effects on ED and testosterone levels. Methods: We systematically searched PubMed, Embase, and Cochrane databases (up to January 19, 2025) for studies comparing GLP-1RA therapy to placebo or other antidiabetic agents in adults with T2DM and/or obesity. The measured outcomes were the International Index of Erectile Function-5 (IIEF-5) score and total testosterone levels, along with sex hormone-binding globulin (SHBG) levels, which help determine testosterone bioavailability. This study was registered in PROSPERO (CRD42025640594). We used a random-effects model to analyze all outcomes. Heterogeneity was assessed using the I² statistic. Review Manager 5.4 (Cochrane Foundation) was used for statistical analysis. Results: Of 1,319 screened studies, 71 underwent full-text review, and four met inclusion criteria. These included one randomized controlled trial, one prospective study, and two retrospective observational studies, with a total of 396 participants (199 receiving GLP-1RA therapy and 197 in the control group). While the mean difference suggested a potential improvement in IIEF-5 scores (higher scores indicate better erectile function) in the GLP-1RA group (MD: 2.84), it was not statistically significant (95% CI: −2.89 to 8.57). Similarly, no statistically significant differences were observed between the GLP-1RA and control groups for total testosterone levels (MD: 53.37 ng/dL, 95% CI: -32.6 to 139.34 ng/dL) or SHBG levels (MD: 4.29 nmol/L, 95% CI: -1.87 to 10.46 nmol/L), although the mean differences suggested a potential improvement. Conclusion: Although weight loss and better glycemic control can improve erectile dysfunction and testosterone levels, this meta-analysis of four studies found no statistically significant effects of GLP-1RAs on erectile dysfunction, total testosterone, or SHBG levels. Given the limited number of studies and variability in study designs, further research, particularly large randomized controlled trials, is needed to clarify the impact of GLP-1RAs on male reproductive health. Presentation: Saturday, July 12, 2025

  PublisherOA PDFDOI

Recent grants

• Distinguishing inflammatory Th17 subsets through using an autoimmune Th17-selective inhibitor

  NIH · $207k · 2022–2026

• Distinguishing inflammatory Th17 subsets through using an autoimmune Th17-selective inhibitor

  NIH · $233k · 2022–2023

• Dissecting functions of IL-23-dependent inflammatory Th17 cells

  NIH · $1.8M · 2022–2028

Frequent coauthors

• Zuoming Sun

  City of Hope

  45 shared

• Ke Lan

  Zhongnan Hospital of Wuhan University

  43 shared

• George L. King

  Joslin Diabetes Center

  43 shared

• Deguang Liang

  Chinese Academy of Sciences

  41 shared

• Andrew Bateman

  McGill University Health Centre

  27 shared

• Subha Sen

  University of California, Los Angeles

  24 shared

• Fei Wang

  ShanghaiTech University

  20 shared

• Armido Studer

  University of Münster

  20 shared

Education

• Ph.D, Institute Pasteur of Shanghai

  Chinese Academy of Sciences

  2011