Huang-Ge Zhang, Ph.D.

Research Interests

Autoimmune Diseases and Cancer Immunology
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 strategies for deletion of antigen specific auto-reactive T cells, using antigen presenting cells pulsed with an auto-antigen and armed with apoptosis molecules such as Fas ligand or TRAIL antigen. I hope to develop such strategies to ultimately treat T cell mediated autoimmune diseases.

Selected Publications (Selected from 99 peer-reviewed publications)

1. Teng Y, Ren Y, Xu X, Mu J, Samykutty A, Zhuang X, Deng Z, Zhang L, Merchant M, Yan J, Miller D, Kumar A, and Zhang HG. Major vault protein (MVP) dependent sorting tumor suppressor miR-193a into tumor exosomes promotes colon cancer progression. Nature Communications, 2017, In press

2. Deng Z, RongY, Teng Y, Zhuang X, Samykutty A, Mu J, Zhang L, Cao P, Yan J, Miller D and Zhang HG. Exosomes miR-126a released from MDSC induced by DOX treatment promotes lung metastasis. Oncogene, 2016, 1-13

3. Zhuang X, Teng Y, Samykutty A, Mu J, Deng Z, Zhang L, Cao P, Rong Y, Yan J, Miller D, Zhang HG. Grapefruit-derived Nanovectors Delivering Therapeutic miR17 Through an Intranasal Route Inhibit Brain Tumor Progression. Mol Ther. 2016 Feb;24(1):96-105.

4. Teng Y, Mu J, Hu X, Samykutty A, Zhuang X, Deng Z, Zhang L, Cao P, Yan J, Miller D, Zhang HG. Grapefruit-derived nanovectors deliver miR-18a for treatment of liver metastasis of colon cancer by induction of M1 macrophages. Oncotarget. 2016 Mar 25

5. Zhang HG, Cao P, Teng Y, Hu X, Wang Q, Yeri AS, Zhuang X, Samykutty A, Mu J, Deng ZB, Zhang L, Mobley JA, Yan J, Van Keuren-Jensen K, Miller D. Isolation, identification, and characterization of novel nanovesicles. Oncotarget. 2016 May 12.

6. Qilong Wang, Yi Ren, Jingyao Mu, Nejat K Egilmez, Xiaoyin Zhuang, Zhongbin Deng,  Lifeng Zhang, Jun Yan, Donald Miller, and Huang-Ge Zhang. Grapefruit-derived nanovectors use an activated leukocyte trafficking pathway to deliver therapeutic agents to  inflammatory tumor site. Cancer Research, 2015, DOI: 10.1158/0008-5472.

7. Zhongbin Deng, Jingyao Mu, Michael Tseng, Binks Wattenberg, Xiaoying Zhuang,  Nejat K. Egilmez, Qilong Wang, Lifeng Zhang, James Norris, Haixun Guo, Jun Yan, Bodduluri Haribabu,Donald Miller & Huang-Ge Zhang. Enterobacteria-secreted particles induce  production of exosome-like S1P-containing particles by intestinal epithelium to drive Th17- mediated tumorigenesis. 2015, Nat Commun doi:10.1038/ncomms7956

8. 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.

9. Wang B, Zhuang X, Deng ZB, Jiang H, Mu J, Wang Q, Xiang X, Guo H, Zhang L, Dryden, Yan J, Miller D, Zhang HG. Targeted drug delivery to intestinal macrophages by bioactive  nanovesicles released from grapefruit. Mol Ther. 2014, 22(3):522-34. PMCID:PMC3944329

10. Deng ZB, Zhuang X, Ju S, Xiang X, Mu J, Wang Q, Hong J, Zhang L, Kronenberg M, Yan,  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

11. 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. PMID: 23752315.

12. 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.

13. Jiang H, Wang P, Wang Q, Deng ZB, Zhuang X, Mu J, Zhang L, Wang B, Jun Y, Miller D,  Zhang HG. Restoration of miR17/20a in Solid Tumor Cells Enhances the Natural Killer Cell Antitumor Activity by Targeting Mekk2. Cancer Immunol Res. 2014; PMID: 24801835

14. 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

15. Sun D, Zhuang X, Zhang S, Deng ZB, Grizzle W, Miller D, Zhang HG. Exosomes are endogenous nanoparticles that can deliver biological information between cells. Adv Drug Deliv Rev. 2013 Mar;65(3):342-7.

16. Deng Z, Zhuang X,  Ju S, Xiang X,  Mu J, Wang Y, Hong J, Zhang L, Kronenberg K, Yan J, Miller D,  and Zhang HG. Intestinal mucus-derived nanoparticle–mediated activation of Wnt/β-catenin signaling plays a role in induction of liver natural killer T cell anergy in mice. Hepatology, 2012 Sep 18. 10.1002

17. Deng ZB, Poliakov A, Hardy RW, Clements R, Liu C, Liu Y, Wang J, Xiang X, Zhang S, Zhuang X, Shah SV, Sun D, Michalek S, Grizzle WE, Garvey T, Mobley J, Zhang HG. (2009) Adipose tissue exosome-like vesicles mediate activation of macrophage-induced insulin resistance. Diabetes, 58(11):2498-505