Huang-Ge Zhang, Ph.D.

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 81 peer-reviewed publications)

1.    Jiang G, Hajrasouliha A, Lu H,  Kaplan H,  Zhang HG, Shao H. Exosomes from retinal astrocytes contain anti-angiogenic components   that      inhibit laser-induced choroidal neovascularization, 2013, JBC, In press

2. Wang B, Zhuang X, Deng Z, Jiang H, Mu J, Wang Q, Xiang X, Guo X, Zhang L, Dryden G, Yan J, Miller D, and Zhang HG. Targeted drug delivery to intestinal macrophages by bioactive nanovesicles released from grapefruit. 2013, Molecualr Therapy, In press

3. Wang Q, Zhuang X, Mu J, Deng Z, 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, In press

4.    Ju S, Mu J, Dokland t, Zhuang X, Wang Q, Jiang H, Xiang X, Deng Z, Wang B, Zhang L, Roth M, Welti R, Mobley J, Jun Y, Miller d, and Zhang HG. Grape exosome-like nanoparticles induce intestinal stem cells and protect mice from DSS induced colitis. Molecular Therapy, 2013, In press

5.    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. Exosomes-Like Nanoparticles from Intestinal Mucosal Cells Carry Prostaglandin E2 and Suppress Activation of Liver NKT Cells. Journal of Immunology, 2013, in press

6.    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

7.    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 HGTumor 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.

8.    Zhuang X,Xiang X,Jiang H, Ju S, Zhang L, Mu J, Miller D, Grizzle W, and Zhang HG. (2011) Treatment of brain inflammatory diseases by exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Molecular Therapy,19(10):1769-79

9.    Deng Z, Pardi R,Cheadle W,Xiang X,Grizzle W, Miller D, MountzJ, and Zhang HG. (2011) Plant homologue constitutive photomorphogenesis 9 (COP9) signalosome  subunit CSN5 regulates innate immune responses in macrophages. Blood, 117(18):4796-804

10.    Xiang X,Zhuang X,Jiang H, Ju S, Zhang L, Mu J, Miller D, Grizzle W, and Zhang HG. (2011) miR-155 promotes macroscopic tumor formation yet inhibits tumor dissemination from mammary fat pads to the lung by preventing EMT. Oncogene, 30(31):3440-53

11.   Zhang HG,Grizzle WE. (2011) Exosomes and cancer: a newly described pathway of immune suppression.Clin Cancer Res. 1;17(5):959-64

12. Sun DZhuang XXiang XLiu YZhang SLiu CBarnes SGrizzle WMiller D,Zhang HG (2010) A Novel Nanoparticle Drug Delivery System: The Anti-inflammatory Activity of Curcumin Is Enhanced When Encapsulated in Exosomes. Molecular Therapy,18(9):1606-14

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

14. 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. Diabetes58(11):2498-505