Education
PhD 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
Research Interests
The research in my lab is focused on immunology and cancer biology with a specific emphasis on alcohol-related immunotoxicology 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 exacerbate viral infection and decrease the survival of alcoholics with cancer. It is not known how alcohol consumption modulates antiviral and anti-tumor immunity. We have been using a chronic alcohol-consuming model in which different types of cancer cells are 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.
Major findings:
- Alcohol consumption decreases peripheral NK cells and diminishes NK cell cytolytic activity by compromising NK cell release from the bone marrow and by impairing NK cell maturation in the periphery. Alcohol-induced deficiency in IL-15 availability plays a key role in NK cell dysfunction.
- Chronic alcohol consumption increases T cells that exhibit a memory-phenotype through induction of a process called homeostatic proliferation. These Memory-like T cells produce high levels of interferon (IFN)-γ.
- Chronic alcohol consumption inhibits melanoma lung metastasis through an IFN-γ-dependent process.
- Chronic alcohol consumption induces myeloid-derived suppressor cells (MDSC), inhibits memory T cells, especially tumor-specific T cell expansion, and accelerates T cell dysfunction in tumor-bearing mice. Thus, anti-tumor immune responses are compromised.
- 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.
- Chronic alcohol consumption increases iNKT cells, and enhances iNKT cell maturation and activation through acetaldehyde-mediated modulation of lipid metabolism. With tumor progression alcohol consumption reverses iNKT cell cytokine profile from Th1-dominant cytokines to Th2-dominant inhibitory cytokines.
- Chronic alcohol consumption enhances cancer-associated cachexia through accelerating the degradation of adipose tissues and atrophy of skeletal muscle.
Based on these findings, our current research is focused on the following: 1) use murine cytomegalovirus and hepatitis C virus models to study how alcohol affects antiviral immunity; 2) investigate the cellular and molecular mechanism of how alcohol consumption impairs NK cell and CD8+ T cell antitumor immunity through inducing MDSC/iNKT/B cell-dominant inhibitory immune network; 3) study the signaling pathways governing alcohol-enhanced cancer-associated cachexia; 4) Develop an NKT cell-based tumor immunotherapy is also a high priority in our current research.
Selected Publications
Li Y, Zhang F, Modrak S, Little A, Zhang H. Chronic alcohol consumption enhances skeletal muscle wasting in mice bearing cachectic cancers: the role of TNF-a/myostatin axis. Alcohol Clin Exp Res. 2020; 44(1):66-77. doi: 0.1111/acer.14221. Epub 2019 Nov 11. PMID: 31657476
Little A, Li Y, Zhang F, Zhang H. Chronic alcohol consumption exacerbates murine cytomegalovirus infection via impairing nonspecific and specific NK activation in mice. FASEB BioAdvancves. 2019; 1(1): 18-31. https://doi.org/10.1096/fba.1019. PMID: 32123809
Dakup P, Porter K, Little A, Gajula R, Zhang H, Skornyakov E, Kemp M, Van Dongen H and Gaddameedhi S. The circadian clock regulates cisplatin-induced toxicity and tumor regression in melanoma mouse and human models. Oncotarget. 2018; 9:14524-14538. https://doi.org/10.18632/oncotarget.24539
Wang B, Wang Z, de Avila JM, Zhu MJ, Zhang F, Gomez NA, Zhao L, Tian Q, Zhao J, Maricelli J, Zhang H, Rodgers BD, Du M. Moderate alcohol intake induces thermogenic brown/beige adipocyte formation via elevating retinoic acid signaling. FASEB J. 2017 Oct;31(10):4612-4622. doi: 10.1096/fj.201700396R. Epub 2017 Jul 5. PMID: 28679528
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. 2017 Apr;101(4):1015-1027. doi: 10.1189/jlb.1A0716-298RR. Epub 2016 Nov 11. PMID: 27837016.
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.
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.
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.
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. PMID: 22753935 (*Corresponding author).