Huang-Ge Zhang, Ph.D.

Research Interests

Autoimmune Diseases, Cancer Immunology, and Edible Plant Exosomes Nanotechnology
My research is recently focused upon understanding how the ubiquitin pathway regulates intracellular signal transduction pathways that transfer key information from the extracellular to the intracellular environment, resulting in coordinated cellular responses. More specifically, I am interested in the ubiquitin pathway’s role of apoptosis in 1) autoimmune diseases and 2) cancer immunosuppresssion. In cancer immunosuppression, my research focuses on the elucidation of the cellular and molecular basis for the role of tumor exosomes and exosomal tumor antigens in the development of T- cell dependent breast cancer and the mechanism underlying tumor immunosuppression mediated by tumor excreted exosomes. In autoimmune diseases, TNF-alpha plays a critical role in the progression of rheumatoid arthritis. Constant activation of TNF-alpha signaling results in chronic inflammation and erosive arthritis, as confirmed in the human TNF-alpha transgenic mice model. Our research focuses on how Jab1 regulates TNF-alpha anti- and pro- apoptosis pathways in rheumatoid arthritis synovial fibroblasts. We also develop Edible Plant Exosomes Nanotechnology: An emerging paradigm shift in drug delivery:

Selected Publications (Selected from 152 peer-reviewed publications)

  1. Sriwastva M, Teng Y, Mu J, Xu F, Kumar A, Sundaram K, Kumar R, Xu Q, Hood J, Zhang L, Yan J, Merchant M, Park J, Dryden G, Egilmez N, Zhang H-G. An extracellular vesicular mutant KRAS-associated protein complex promotes lung inflammation and tumor growth J Extracell Vesicles 2023 Vol. 12 Issue e12307



  2. Teng T, Mu J, Xu F, Zhang X, Sriwastva M, Liu Q, Li X, Kumar A, Lei C, Hu X, Zhang L, Park J, Rouchka E, Zhang X, Yan J, Merchant M, and Zhang HG, Gut Bacterial Isoamylamine Promotes Age-Related Cognitive Dysfunction by Promoting Microglial Cell Death. Cell Host & Microbe, 2022, 30, 944–960 ^ Research Highlights, Ursula Hofer (2022) Gut–brain axis in ageing. Nature Review Microbiology (20) (446)
  3. Sriwastva M, Deng Z, Wang B, Teng Y, Kumar A, Sundaram K, Mu J, Lei C, Dryden G, Xu F, Zhang L,  J, Zhang X, Park J, Merchant M, Egilmez N, and Zhang HG. Exosome-like nanoparticles from Mulberry bark prevent DSS-induced colitis via the AhR/COPS8 pathway EMBO Rep 2022 Vol. 23 Issue 3 Pages e53365
  4. Xu F, MU J, Teng Y, Zhang X, Sundaram K, Sriwastva M, Kumar A, Lei C, Zhang L, Liu Q, Yan J, McClain J, Merchant M, and Zhang HG. Restoring Oat Nanoparticles Mediated Brain Memory Function of Mice Fed Alcohol by Sorting Inflammatory Dectin-1 Complex into Microglial Exosomes, Small, 2021 Dec 13;e2105385
  5. Kumar A, Zhang L, Yan J, Sriwastva M, Park J, Merchant ML, and Zhang HG. High-fat dietinduced upregulation of exosomal phosphatidylcholine contributes to insulin resistance, Nature Communications, 2021, 12:213
  6. Teng T, Ren Y, Sayed M, Hu X, Lei C, Kumar A, Hutchins E, Mu J, Deng Z, Luo C, Sriwastva M,Zhang L, Hsieh M, Reiman R, Bodduluri H, Jun Y, Jala R, Miller D, Keuren-Jensen K, Merchant M,McClain C, Park J, Egilmez NK, and Zhang HG. Plant-derived exosomal microRNAs shape the gut microbiota. Cell Host & Microbe, 2018, Volume 24, Issue 5, 637– 652.  Research Highlights, Jennifer K.Spinler, Vivekanudeep Karri, Kendal D.Hirschi (2019) Planting the Microbiome. Trends in Microbiology Volume 27, Issue 2, Pages 90-93Research Highlights, Kristina Campbell (2020) Do the microRNAs we eat affect gene expression? Nature OUTLOOK, 17 June 2020
  7. Yun Teng, Fangyi Xu, Xiangcheng Zhang, Jingyao Mu, Mohammed Sayed, Xin Hu, Chao Lei, Mukesh Sriwastva, Anil Kumar, Kumaran Sundaram, Lifeng Zhang, Juw Won Park, Shao-Yu Chen, Shuangqin Zhang, Jun Yan, Michael L Merchant, Xiang Zhang, Craig J McClain, Jennifer K Wolfe, Robert S Adcock, Donghoon Chung, Kenneth E Palmer, Huang-Ge Zhang. Plant-derived exosomal microRNAs inhibit lung inflammation induced by exosomes SARSCoV-2 Nsp12, Mol Therapy. 2021 May 11;S1525-0016(21)00257-4
  8. Anil Kumar, Yi Ren, Kumaran Sundaram, Jingyao Mu, Mukesh K Sriwastva, Gerald W Dryden, Chao Lei, Lifeng Zhang, Jun Yan, Xiang Zhang, Juw Won Park, Michael L Merchant, Yun Teng, Huang-Ge Zhang. miR-375 prevents high-fat diet-induced insulin resistance and obesity by targeting the aryl hydrocarbon receptor and bacterial tryptophanase (tnaA) gene, Theranostics.2021 Feb 19;11(9):4061-4077.
  9. Anil Kumar, Kumaran Sundaram, Jingyao Mu, Gerald W Dryden, Mukesh K Sriwastva, Chao Lei, Lifeng Zhang1, Xiaolan Qiu1, Fangyi Xu, Jun Yan, Xiang Zhang, Juw Won Park, Michael L Merchant, Henry C L Bohler7, Baomei Wang, Shuangqin Zhang, Chao Qin, Ziying Xu, Xianlin Han, Craig J McClain, Yun Teng, Huang-Ge Zhang. High-fat diet-induced upregulation of exosomal phosphatidylcholine contributes to insulin resistance, Nature Communications.2021 Jan 11;12(1):213.
  10. Qi-Long Wang, XiaoYing Zhuang, Mukesh K Sriwastva, Jingyao Mu, Yun Teng , Zhongbin Deng, Lifeng Zhang, Kumaran Sundaram, Anil Kumar, Donald Miller, Jun Yan, Huang-Ge Zhang. Blood exosomes regulate the tissue distribution of grapefruit-derived nanovector via CD36 and IGFR1 pathways Theranostics 2018 Sep 9;8(18):4912-4924
  11. Zhuang X, Deng ZB, Mu J, Zhang L, Yan J, Miller D, Feng W , McClain CJ, Zhang HG. Ginger-derived nanoparticles protect against alcohol-induced liver damage. J Extracell Vesicles. 2015 Nov 25;4:28713. PMCID:    PMC4662062 
  12. Deng ZB, Zhuang X, Ju S, Xiang X, Mu J, Wang Q, Hong J, Zhang L, Kronenberg M, Yan J, Miller D, Zhang HG.: Intestinal mucus-derived nanoparticles mediate activation of Wnt/βcatenin signaling plays a role ininduction of liver NKT cell anergy.  Hepatology. 2013 57(3):1250-61. PMID: 22991247
  13. Deng ZB, Liu Y, Liu C, Xiang X, Wang J, Cheng Z, Shah SV, Zhang S, Zhang L, Zhuang X, Michalek S, Grizzle WE, Zhang HG. (2009) Immature myeloid cells induced by a high fat diet contribute to liver inflammation. Hepatology, 50(5):1412-20. PMCID: PMC2852608
  14. Wang Q, Zhuang X, Mu J, Deng ZB, Jiang H, Xiang X, Wang B, Yan J, Miller D, Zhang HG.: Delivery of therapeutic agents by nanoparticles made of grapefruit-derived lipids.  Nat Communications. 2013;4:1867. doi: 10.1038/ncomms2886. PMID: 23695661.
  15. Wang Q, Ren Y, Mu J, Egilmez NK, Zhuang X, Deng Z, Zhang L, Yan J, Miller D, Zhang HG. Grapefruit-derived nanovectors use an activated leukocyte trafficking pathway to deliver therapeutic agents to inflammatory tumor sites. Cancer Res. 2015 Apr 16. pii: canres.3095. PMID:    25883092  Research Highlights, Andrew Z. Wang, More than just a fruit: Grapefruit-derived nanovectors deliver cancer drugs, Science Translational Medicine  2015: Vol. 7, Issue 288, pp. 288ec83
  16. Teng Y, Ren Y, Deng Z, Zhuang X, Samykutty A, Mu J, Zhang L, Cao P, Yan J, Miller D and H-G Zhang. MVP-mediated exosome sorting of miR-193a promotes colon cancer progression. Nature Communications, 2017 Feb 17;8:14448. doi: 10.103
  17. Deng Z, Mu J, Tseng M, Wattenberg B, Zhuang X, Egilmez NK, Wang Q, Zhang L, Norris J, Guo H, Yan J, Haribabu B, Miller D, Zhang HG. Enterobacteria-secreted particles induce production of exosome-like S1P-containing particles by intestinal epithelium to drive Th17mediated tumorigenesis.   Nature Communications. 2015 Apr 24;6:6956, PMCID:  PMC4410277
  18. Huang-Ge Zhang, Di Liu, Yuji Heike, PingAr Yang, Zheng Wang, Xiaoyun Wang, David T. Curiel, Tong Zhou & John D. Mountz. Induction of specific T-cell tolerance by adenovirustransfected, Fas ligand-producing antigen-presenting cells. Nature Biotechnology volume 16, pages1045–1049 (1998)