Huang-Ge Zhang, DVM, Ph.D.

Education:

DVM, Medicine, Veterinary College of Inner Mongolia University, Huhhet, PRC; 1982
M.S., Virology, Veterinary College of Inner Mongolia University, Huhhet, PRC; 1985
Ph.D., Viral Immunology, Mississippi State University, Mississippi State, MS; 1994
Post-doctoral Fellow, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 1995-1998

Curriculum Vitae

Current Positions:

Professor, Department of Microbiology & Immunology, University of Louisville
Member, Brown Cancer Center, University of Louisville
The Founders Chair in Cancer Research, Brown Cancer Center, University of Louisville

Contact Information:

Clinical & Translational Research Building, Room 309
University of Louisville
505 South Hancock Street
Louisville, KY 40202
Phone:  502-500-3993
Fax: 502-852-2123

Email: H0zhan17@louisville.edu

Research Description:

The Zhang lab is interested in exosomes biology and nanotechnology and summarized below:

  1. Interspecies communication through plant exosome-like nanoparticle. The role for edible plant exosome-like nanoparticles mediating interspecies communications has been demonstrated recently. The data suggest that significant amounts of edible plant exosome-like nanoparticles (ELNs) are taken up by intestinal macrophages and stem cells. Their biological effects are crucial for maintaining intestinal homeostasis and gut immune tolerance. This initial discovery opens up a new avenue for further exploring the cellular and molecular mechanisms underlying how plant exosome-like nanoparticles mediate induction of gut immune tolerance.
  2. Edible plant exosome-like nanoparticles as a delivery vehicle.  Unlike the situation with artificially synthesized nanoparticles, naturally released nano-sized exosomes derived from the tissue of edible plants including grapefruit, grapes, ginger, and tomatoes, and produced them in large quantities. Using both in vitro cell culture models as well as mouse models, we have shown that grapefruit exosome-like nanoparticles are highly efficient for delivering a variety of therapeutic agents including drugs, DNA expression vectors, siRNA and antibody.
  3. Tumor exosomes mediated immunosuppression:  One of my main basic science research focuses has been to understand the mechanisms by which tumor cells communicate with immune cells via tumor exosomes. My laboratory has made several fundamental discoveries that involve the role of tumor exosomes in immunosuppression and in metastasis. My group was the first to present findings that showed tumor exosome-mediated blocking of IL-2-mediated activation of NK cells and their cytotoxic response to tumor cells. Subsequently, my group showed that tumor exosomes not only inhibit differentiation of bone marrow dendritic cells, but also induce myeloid-derived suppressor cells in a Myd88 dependent manner. Tumor microenvironmental factors play a crucial role in the potency of tumor exosome-mediated induction of myeloid-derived suppressor cells (MDSCs).

Literature Cited:

  1. Ding C, Shrestha R, Zhu X, Geller AE, Wu S, Woeste MR, Li W, Wang H, Yuan F, Xu R, Chariker JH, Hu X, Li H, Tieri D, Zhang HG, Rouchka EC, Mitchell R, Siskind LJ, Zhang X, Xu XG, McMasters KM, Yu Y, Yan J.  Inducing trained immunity in pro-metastatic macrophages to control tumor metastasis.  Nature Immunology 2023 Feb;24(2):239-254.  doi: 10.1038/s41590-022-01388-8 .  Epub 2023 Jan 5.  PMID: 36604547.
  2. Geller AE, Shrestha R, Woeste MR, Guo H, Hu X, Ding C, Andreeva K, Chariker JH, Zhou M, Tieri D, Watson CT, Mitchell RA, Zhang HG, Li Y, Martin II RCG, Rouchka EC, Yan J.  The induction of peripheral trained immunity in the pancreas incites anti-tumor activity to control pancreatic cancer progression.  Nature Communications 2022 Feb 9;13(1):759.  doi: 10.1038/s41467-022-28407-4 .  PMID: 35140221.  PMCID: PMC8828725.
  3. Kumar A, Sundaram K, Mu J, Dryden GW, Sriwastva MK, Lei C, Zhang L, Qiu X, Xu F, Yan J, Zhang X, Park JW, Merchant ML, Bohler HCL, Wang B, Zhang S, Qin C, Xu Z, Han X, McClain CJ, Teng Y, Zhang HG.  High-fat diet-induced upregulation of exosomal phosphatidylcholine contributes to insulin resistance.  Nature Communications 2021 Jan 11;12(1):213.  doi: 10.1038/s41467-020-20500-w.  PMID: 33431899.  PMCID: PMC7801461.
  4. Teng Y, Ren Y, Sayed M, Hu X, Lei C, Kumar A, Hutchins E, Mu J, Deng Z, Luo C, Sundaram K, Sriwastva MK, Zhang L, Hsieh M, Reiman R, Haribabu B, Yan J, Jala VR, Miller DM, Van Keuren-Jensen K, Merchant ML, McClain CJ, Park JW, Egilmez NK, Zhang HG.  Plant-derived exosomal microRNAs shape the gut microbiota.  Cell Host & Microbe 2018 Nov 14;24(5):637-652.e8.  doi: 10.1016/j.chom.2018.10.001.  Epub 2018 Oct 25.  PMID: 30449315.  PMCID: PMC6746408 .
  1. Teng Y, Ren Y, Hu X, Mu J, Samykutty A, Zhuang X, Deng Z, Kumar A, Zhang L, Merchant ML, Yan J, Miller DM, Zhang HG.  MVP-mediated exosomal sorting of miR-193a promotes colon cancer progression.  Nature Communications 2017 Feb 17;8:14448. doi: 10.1038/ncomms14448.  PMID: 28211508.  PMCID: PMC5321731 .
  1. 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 Th17-mediated tumorigenesis.  Nature Communications 2015 Apr 24;6:6956.  doi: 10.1038/ncomms7956.  Erratum in: Nature Communications 2016;7:11348.  PMID: 25907800.  PMCID: PMC4410277.
  2. Mu J, Zhuang X, Wang Q, Jiang H, Deng ZB, Wang B, Zhang L, Kakar S, Jun Y, Miller D, Zhang HG. Interspecies communication between plant and mouse gut host cells through edible plant derived exosome-like nanoparticles.  Molecular Nutriion & Food Research 2014;58(7):1561-73.  PMID: 24842810.  PMCID: PMC4851829.
  3. 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.  Nature Communications 2013;4:1867.  doi: 10.1038/ncomms2886.  PMID: 23695661.  PMCID:  PMC4396627.
  4. 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/β-catenin signaling plays a role ininduction of liver NKT cell anergy.  Hepatology 2013;57(3):1250-61.  PMID: 22991247.  PMCID: PMC4414328.
  5. Zhuang X, Xiang X, Grizzle W, Sun D, Zhang S, Axtell RC, Ju S, Mu J, Zhang L, Steinman L, Miller D, Zhang HG.  Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain.  Molecular Therapy 2011 Oct;19(10):1769-79.  PMID: 21915101.  PMCID:  PMC3188748.

PubMed Information