Huang-Ge Zhang, Ph.D.

Education:

B.S., Medical School of Inner Mongolia, Huhhet, PRC, 1982
DVM, Veterinary Medical School of Inner Mongolia, 1985
Ph.D., Molecular Viology, Mississippi State University, Mississippi State, MS, 1994
Postdoctoral Fellowship, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham.  1998

Curriculum Vitae

Current Positions:

Tenured Professor, Department of Microbiology & Immunology, University of Louisville.
Director of Chemoprevention Grogram, James Brown Cancer, University of Louisville
The Founders Chair in Cancer Research at the James Graham Brown Cancer Center,  University of Louisville

Contact Information:

Clinical Translational Research Building, Room 309
University of Louisville
505 Hancock St.
Louisville, KY 40202, USA
Phone 502-852-8968
Fax 502-852-8623
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. Deng ZB, Poliakov A, Hardy RW, Clements R, Liu C, Liu Y, Wang J, Xiang X, Zhang S, Zhuang X, Shah SV, un D, Michalek S, Grizzle WE, Garvey T, Mobley J, Zhang HG.  Adipose tissue exosome-like vesicles mediate activation of macrophage-induced insulin resistance. Diabetes. 2009 Nov;58(11):2498-505. PMCID: PMC2768161.
  2. 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
  3. Deng ZB, Zhuang X, Ju S, Xiang X, Mu J, Liu Y, Jiang H, Zhang L, Mobley J, McClain C, Feng W, Grizzle W, Yan J, Miller D, Kronenberg M, Zhang HG.:  Exosome-like nanoparticles from intestinal mucosal cells carry prostaglandin E2 and suppress activation of liver NKT cells.  J Immunol, 2013, 190(7):3579-89. PMID: 23467936.
  4. 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
  5. Ju S, Mu J, Dokland T, Zhuang X, Wang Q, Jiang H, Xiang X, Deng ZB, Wang B, Zhang L, Roth M, Welti R, Mobley J, Jun Y, Miller D, Zhang HG.: Grape exosome-like nanoparticles induce intestinal stem cells and protect mice from DSS-induced colitis.  Mol Ther. 2013 Jul;21(7):1345-57. doi: 10.1038/mt.2013.64. PMID: 23752315.
  6. 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. Mol Nutr Food Res. 2014; 58(7):1561-73. PMID:  24842810
  7. Wang B, Zhuang X, Deng ZB, Jiang H, Mu J, Wang Q, Xiang X, Guo H, Zhang L, Dryden G, Yan J, Miller D, Zhang HG. Targeted drug delivery to intestinal macrophages by bioactive nanovesicles released from grapefruit. Mol Ther. 2013 Aug 13. doi: 10.1038, PMID: 23939022
  8. Liu C, Yu S, Zinn K, Wang J,   Zhang L,  Jia J, Kappes JC, Barnes S, Kimberly RP, Grizzle WE, Zhang HG.
  9. (2006). Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function. J Immunol. 1;176(3):1375-85. PMID:16424164
  10. b.  Yu SH, Liu C, Su K, Wang J, Zhang L,  Yu S, Grizzle G, Kimberly RP, and Zhang HG. (2007) Tumor exosomes block bone marrow dendritic cell differentiation. Journal of Immunology, 178: 6867-75 PMID: 17513735
  11. c.  Xiang X, Poliakov A, Liu C, Liu Y, Deng Z, Wang J, Cheng Z, Shah S, Wang G, Zhang L, Grizzle W, Mobley j, and Zhang HG (2009) Induction of myeloid-derived suppressor cells by tumor exosomes. International Journal of Cancer, 124:2621-33 PMCID: PMC2757307.
  12. d.  Deng Z, Cheng Z, Xiang X, Yan J, Zhuang X, Liu C, Jiang H, Ju S, Zhang L, Grizzle W, Mobley J, Roman J, Miller D, Zhang HG. Tumor cell cross talk with tumor-associated leukocytes leads to induction of tumor exosomal fibronectin and promotes tumor progression., Am J Pathol. 2012 Jan;180(1):390-8, PMCID: PMID: 22067905
  13. Sun D, Zhuang X, Xiang X, Liu Y, Zhang S, Liu C, Barnes S, Grizzle W, Miller D, Zhang HG.  A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes. Mol Ther. 2010 Sep;18(9):1606-14. PMCID: PMC2956928
  14. 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. Mol Ther. 2011 Oct;19(10):1769-79 PMCID:    PMC3188748
  15. 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 Commun. 2013;4:1867. doi: 10.1038/ncomms2886. PMID: 23695661.

PubMed Information