Hui Zhang, Ph.D.
Ph.D. in genetics, Institute of Hydrobiology, the Chinese Academy of Sciences, China
Master of Science in biology, Shanxi University, China
Bachelor of Science in biology, Henan Normal University, China
My research focus is the immunotoxicology of alcohol with a specific emphasis on tumor immunology and immunotherapy. Alcohol consumption causes organ damage and increases the incidence of infectious diseases and cancers. The immune system is severely affected by alcohol consumption. The deterioration of the immune system is known to decrease the survival of alcoholics with cancer. It is not known how alcohol consumption modulates anti-tumor immunity. We have been using a chronic alcohol-consuming model in which melanoma is inoculated into mice to study the mechanism of how alcohol consumption affects natural killer (NK), NKT, T and B cell function and anti-tumor immunity.
1) Alcohol consumption decreases peripheral NK cells and diminishes NK cell cytolytic activity by compromising NK cell release from the bone marrow, and it also decreases mature NK cells in the periphery.
2) Chronic alcohol consumption increases T cells that exhibit a memory-phenotype. These cells increase in alcohol consuming mice through induction of a process called homeostatic proliferation. Memory T cells produce high levels of interferon (IFN)-γ.
3) Chronic alcohol consumption inhibits melanoma lung metastasis through an IFN-γ dependent process.
4) Chronic alcohol consumption induces myeloid-derived suppressor cells (MDSC), inhibits memory T cells, especially melanoma-specific T cell expansion, and accelerates T cell dysfunction in melanoma-bearing mice. Thus, anti-tumor immune responses are compromised.
5) Chronic alcohol consumption induces lymphopenia and decreases mature B cells in the blood of melanoma-bearing mice by impairing the sphingosine-1-phosphate (S1P)/ S1P1 receptor (S1PR1) signaling pathway.
6) Chronic alcohol consumption increases NKT cells and modulates NKT cell maturation, cytokine profiles, and production.
Based on these findings, my current research is focused on defining the molecular mechanisms of how alcohol modulates NK cell release from the bone marrow and how it regulates NK cell differentiation in the spleen. I am studying interaction between alcohol and tumors and how this regulates NKT cell activation, proliferation and cytokine profile changes. In addition, I am defining how NKT cells regulate the functions of dendritic, NK and T cells in relation to their role in tumor immunity. Developing an NKT cell-based tumor immunotherapy is also a high priority in my current research.
Zhang F, Little A, Zhang H*. 2016. Chronic alcohol consumption inhibits peripheral NK cell development and maturation by decreasing the availability of IL-15. J Leukoc Biol. 2016 Nov 11. pii: jlb.1A0716-298RR. [Epub ahead of print]. PMID: 27837016. (*Corresponding author).
Gaither K, Little L, McBride A, Garcia S, Brar K, Zhu Z, Zhang F, Meadows G*, Zhang H*. 2016. The immunomodulatory, antitumor and antimetastatic responses of melanoma-bearing normal and alcoholic mice to Sunitinib and ALT-803: A combinatorial treatment approach. Cancer Immunol Immunother. 65(9):1123-34. doi: 10.1007/s00262-016-1876-8. PMID: 27481107. (*Co-Corresponding author).
Chu D, Zhao Q, Yu J, Zhang F, Zhang H, Wang Z. 2016. Nanoparticle Targeting of Neutrophils for Improved Cancer Immunotherapy. Adv Healthc Mater. 5(9):1088-1093. doi: 10.1002/adhm.201500998. PMID: 26989887.
Meadows, GG. and H. Zhang. 2015. Effects of Alcohol on Tumor Growth, Metastasis, Immune Response, and Host Survival. Alcohol Research: Current Reviews, 37(2): 311-330. PMID: 26695753.
Zhang F, Zhu Z, Meadows, GG, Zhang H*. 2015. Chronic alcohol consumption inhibits melanoma growth, but decreases the survival of mice immunized with tumor cell lysate and boosted with alpha-galactosylceramide. International Immunopharmacology. 28(1):359-368. PMID: 26118634 (* Corresponding author).
Zhang H*, Zhu Z, Zhang F, Meadows GG. 2015. Alcohol consumption and antitumor immunity: dynamic changes from activation to accelerated deterioration of the immune system. Adv Exp Med Biol. 815:313-331, PMID: 25427915 (* Corresponding author).
Zhang H*, Zhang F, Zhu Z, Luong D, Meadows GG. 2015. Chronic alcohol consumption enhances iNKT cell maturation and activation. Toxicol Appl Pharmacol., 282(2):139-150. PMID: 25499027 (*Corresponding author).
Liu C, Zhang F, Munske G, Zhang H, Xian M. 2014. Isotope dilution mass spectrometry for the quantification of sulfane sulfurs. Free Radic Biol Med. 76:200-207, PMID: 25152234.
Park CM, Zhao Y, Zhu Z, Pacheco A, Peng B, Devarie-Baez NO, Bagdon P, Zhang H, Xian M. 2013. Synthesis and evaluation of phosphorodithioate-based hydrogen sulfide donors. Mol Biosyst. 9(10):2430-2434. doi: 10.1039/c3mb70145j. PMID: 23917226.
John Powers, Hui Zhang, Logan Battrell, Gary G. Meadows and Grant D. Trobridge. 2012. Establishment of an immunodeficient alcohol mouse model to study the effects of ethanol on human cells in vivo. Journal of Studies on Alcohol and Drugs. 73(6):933-937. PMID: 23036211.
Hui Zhang*, Zhaohui Zhu, and Gary G. Meadows. 2012. Chronic alcohol consumption impairs distribution and compromises circulation of B cells in B16BL6 melanoma-bearing mice. Journal of Immunology. 189(3):1340-1348. (* Corresponding author). PMID: 22753935.
Hui Zhang, Zhaohui Zhu, Jennifer M. Mckinly, Gary G. Meadows. 2011. IFN-γ is essential for the inhibition of B16BL6 melanoma lung metastasis in chronic alcohol drinking mice. Clinical and Experimental Metastasis. 28(3): 301-307. Epub 2011 Jan. 14. PMID: 21234656.
Hui Zhang, Zhaohui Zhu, and Gary G. Meadows, 2011. Chronic alcohol consumption decreases the percentage and number of NK cells in the peripheral lymph nodes and exacerbates B16BL6 melanoma metastasis into the draining lymph nodes. Cellular Immunology. 266(2):172-179. PMID: 20974468.
Hui Zhang and Gary G. Meadows, 2010. Chronic alcohol consumption enhances myeloid-derived suppressor cells (MDSC) in B16BL6 melanoma-bearing mice. Cancer Immunology Immunotherapy. 59(8):1151-1159. PMID: 20229084.
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