Zhenyu Zhong, Ph.D. Titles and Appointments Assistant Professor Schools Medical School | Graduate School Departments Immunology Graduate Programs Cancer Biology, Immunology Biography Dr. Zhenyu Zhong earned his Ph.D. in Immunology at Loyola University Chicago, completed postdoctoral training at the University of California San Diego, and established his independent laboratory at UT Southwestern Medical Center in late 2018 as an Assistant Professor (tenure-track). Across this trajectory, Dr. Zhong’s work has made conceptual advances that helped redefine mitochondria as central signaling hubs that translate cellular stress into innate immune outcomes, thereby shaping how the field understands the logic that initiates, amplifies, and restrains inflammasome-driven inflammation. He established core, tractable control points in NLRP3 biology – linking oxidative stress to inflammasome assembly through TRPM2-mediated Ca²⁺ influx (Nat Commun, 2013), identifying mitophagy as a macrophage-intrinsic brake that enforces a self-limiting inflammatory response (Cell, 2016), and defining a pathway in which new mitochondrial DNA synthesis generates oxidized mitochondrial DNA signals that engage and activate NLRP3 (Nature, 2018). In parallel, he showed how this innate immune circuitry can be productively harnessed for therapy by developing a colorectal cancer vaccine that activates NLRP3 and AIM2 inflammasomes to induce caspase-1–dependent pyroptosis, eradicate intestinal tumors, and nearly triple lifespan in a murine model of intestinal malignancy (Nat Commun, 2017). Extending these mechanistic principles into immunometabolic disease, the Zhong lab demonstrated that prolonged hypernutrition impairs TREM2-dependent efferocytosis – a protective macrophage program – thereby licensing chronic liver inflammation and driving MASH progression (Immunity, 2023), and revealed that obesity rewires macrophage nucleotide metabolism by disrupting SAMHD1 to fuel pathological NLRP3 hyperactivation, thereby precipitating metabolic disease progression (Science, 2026). Guided by the overarching goal of defining how inflammation is initiated, sustained, and resolved – and why obesity and aging can push these programs toward chronic, disease-driving immune states – the Zhong lab couples mechanistic discovery with translational intent. Leveraging CRISPR-based screening, biochemistry/molecular biology, imaging, single-cell “omics” and spatial/temporal transcriptomics, genetic disease models, and AI/ML-driven analysis to uncover biomarkers and actionable control points, the lab aims to convert mechanism into therapeutic logic that restores balanced immune states across immunometabolic disorders, cancer, and neurodegenerative diseases. Research Interest Innate Immunity Mitochondrial Stress Reponse Neuroinflammation Obesity-associated chronic Liver Diseases Tumor Immunology Publications Featured Publications Nucleotide metabolic rewiring enables NLRP3 inflammasome hyperactivation in obesity. Liu D, Zhou C, Wang X, Luo Z, Xu R, Huo S, Guo L, Luo X, Yang S, Click A, Vancil J, Barajas P, Mijares V, Baniasadi H, Yan N, Rehwinkel J, Hancks DC, Chen EH, Liang S, Zhong Z, Science 2026 Jan 391 6782 eadq9006 Prolonged hypernutrition impairs TREM2-dependent efferocytosis to license chronic liver inflammation and NASH development. Wang X, He Q, Zhou C, Xu Y, Liu D, Fujiwara N, Kubota N, Click A, Henderson P, Vancil J, Marquez CA, Gunasekaran G, Schwartz ME, Tabrizian P, Sarpel U, Fiel MI, Diao Y, Sun B, Hoshida Y, Liang S, Zhong Z, Immunity 2022 Dec New mitochondrial DNA synthesis enables NLRP3 inflammasome activation. Zhong Z, Liang S, Sanchez-Lopez E, He F, Shalapour S, Lin XJ, Wong J, Ding S, Seki E, Schnabl B, Hevener AL, Greenberg HB, Kisseleva T, Karin M Nature 2018 Aug 560 7717 198-203 Limiting inflammation - The negative regulation of NF-B and the NLRP3 inflammasome Afonina IS, Zhong Z, Karin M, Beyaert R Nat. Immunol. 2017 Jul 18 8 861-869 Papilloma-pseudovirus eradicates intestinal tumours and triples the lifespan of ApcMin/+ mice. Zhong Z, Zhai Y, Bu P, Shah S, Qiao L Nat Commun 2017 8 Apr 11 15004. Autophagy, Inflammation, and Immunity: A Troika Governing Cancer and Its Treatment. Zhong Z, Sanchez-Lopez E, Karin M Cell 2016 Jul 166 2 288-298 NF-?B Restricts Inflammasome Activation via Elimination of Damaged Mitochondria. Zhong Z, Umemura A, Sanchez-Lopez E, Liang S, Shalapour S, Wong J, He F, Boassa D, Perkins G, Ali SR, McGeough MD, Ellisman MH, Seki E, Gustafsson AB, Hoffman HM, Diaz-Meco MT, Moscat J, Karin M Cell 2016 Feb 164 5 896-910 TRPM2 links oxidative stress to NLRP3 inflammasome activation. Zhong Z, Zhai Y, Liang S, Mori Y, Han R, Sutterwala FS, Qiao L Nat Commun 2013 4 1611 TREM2-expressing macrophages in liver diseases. Wang X, Qiu Z, Zhong Z, Liang S, Trends Endocrinol Metab 2025 May Molecular signatures of long-term hepatocellular carcinoma risk in nonalcoholic fatty liver disease. Fujiwara N, Kubota N, Crouchet E, Koneru B, Marquez CA, Jajoriya AK, Panda G, Qian T, Zhu S, Goossens N, Wang X, Liang S, Zhong Z, Lewis S, Taouli B, Schwartz ME, Fiel MI, Singal AG, Marrero JA, Fobar AJ, Parikh ND, Raman I, Li QZ, Taguri M, Ono A, Aikata H, Nakahara T, Nakagawa H, Matsushita Y, Tateishi R, Koike K, Kobayashi M, Higashi T, Nakagawa S, Yamashita YI, Beppu T, Baba H, Kumada H, Chayama K, Baumert TF, Hoshida Y, Sci Transl Med 2022 Jun 14 650 eabo4474 Results 1-10 of 23 1 2 3 Next Last Honors & Awards CPRIT Individual Investigator Research Award (2025) American Association of Immunologists ASPIRE Award (2024) CPRIT Individual Investigator Research Award (2023) UT Southwestern Circle of Friends Synergy Grant Award (2022) NIH/NIGMS MIRA R35 Award (2021) American Cancer Society IRG Award (2020) Milstein Young Investigator Award, International Cytokine and Interferon Society (2020) NIH/NIAID K22 Career Transition Award (2020) UT Southwestern Circle of Friends Award in Cancer Research (2019) Cancer Prevention Research Institute of Texas (CPRIT) Scholar Recruitment of First-Time, Tenure-Track Faculty Members (2018) University of Texas System Rising STARs Award (2018) American Association for the Study of Liver Diseases (AASLD) Pinnacle Research Award (2017) Prevent Cancer Foundation Board of Directors Award (2017) American Association of Immunologists (AAI) Trainee Achievement Award (2016) Cancer Research Institute Irvington Postdoctoral Fellowship Award (2014) Professional Associations/Affiliations American Association for Cancer Research (2012) American Association for the Study of Liver Diseases (2017) American Association of Immunologists (2010) International Cytokine and Interferon Society (2020)
