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Faculty Detail     Name ZDENEK HEL   Campus Address SHEL 603 Zip 2182 Phone 205-975-7079 E-mail zhel@uab.edu Other websites

Education Undergraduate  Charles University, Prague, Czech Republic    1990  M.Sc.  Graduate  McGill University, Montreal, Canada    1997  Ph.D.  Fellowship  National Institutes of Health, Bethesda, MD, USA    2002  Postdoctoral fellow

Faculty Appointment(s) Appointment Type Department Division Rank Primary  Pathology   Molecular & Cellular Pathology Associate Professor Secondary  Microbiology  Microbiology Assistant Professor Center  Center for AIDS Research  Center for AIDS Research Associate Professor Center  Comprehensive Cancer Center  Comprehensive Cancer Center Associate Professor

Graduate Biomedical Sciences Affiliations Cancer Biology  Immunology  Medical Scientist Training Program  Pathobiology and Molecular Medicine

Biographical Sketch  2011-present Associate Professor, Department of Pathology, Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA. 2003-2011 Assistant Professor, Department of Pathology, Department of Microbiology, UAB, AL, USA. 2003-present Associate Scientist, Center for AIDS Research, Comprehensive Cancer Center, Gene Therapy Center, Mucosal HIV and Immunobiology Center, UAB, AL, USA. 1999-2002 Lecturer, Foundation for Advanced Education in Sciences, National Institutes of Health, Bethesda, MD, U.S.A. 1997- 2002 Postdoctoral Fellow, Laboratory of Animal Models and Retroviral Vaccines (Dr. Genoveffa Franchini), National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. 1991 - 1997 Ph.D. student, Center for the Study of Host Resistance, Research Institute of Montreal General Hospital, McGill University, Montreal, Québec, Canada. 1988 - 1990 Research Assistant, Institute of Molecular Genetics, National Academy of Sciences of Czech Republic, Prague, Czech Republic. Education: 1997- 2002 Postdoctoral Fellowship, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. May, 1997 Ph.D. Degree in Experimental Medicine, with Honors, Department of Experimental Medicine, School of Medicine, McGill University, Montreal, Québec, Canada. June, 1990 M.S. Degree in Biochemistry, with Honors, Department of Biochemistry, School of Natural Sciences, Charles University, Prague, Czech Republic.

Society Memberships Organization Name Position Held Org Link American Association for Cancer Research     http://www.aacr.org/  International AIDS Society    http://www.ias.se/

Research/Clinical Interest Title Immunology and pathogenesis of HIV-1 / AIDS Effect of hormonal contraception on HIV-1 transmission. Design of novel strategies for immunotherapy of cancer. Description Research in our laboratory focuses on the following areas: 1) Pathogenesis of HIV-1 infection. The decline of CD4+ T cells, a hallmark of HIV-1 infection and indicator of disease progression, is caused primarily by chronic activation of immune system; however, the underlying causes of this activation remain unclear. We hypothesize that HIV-1 infection is associated with a severe reduction of IgA responses to common microbial and food antigens proportionally to the extent of CD4+ T cell depletion and polyclonal activation of IgA-producing B cells at mucosal tissues. We investigate whether the inability to mount specific IgA responses results in increased absorption of environmental antigens to the systemic compartment contributing to the chronic activation of CD4+ and CD8+ T cells characteristic for HIV-1 infection. 2) Effect of sex steroid hormones and hormonal contraception on the immunobiology of HIV-1 infection. Worldwide, increasing number of women uses oral or injectable hormonal contraceptives. However, inadequate information is available to aid women and healthcare professionals in weighing the potential risks of hormonal contraceptive use in individuals living with human immunodeficiency virus-1 (HIV-1) or at high risk of infection. Numerous epidemiological studies suggest that progesterone-based contraceptives increase the risk of HIV-1 infection in humans, accelerate disease progression, and increase viral shedding in the genital tract. In contrast to progesterone, systemic or intravaginal treatment with estrogen efficiently protects female rhesus macaques against the transmission of SIV, likely by enhancing the natural protective properties of the lower genital tract mucosal tissue. We investigate the effect of progesterone, medroxyprogesterone, and estrogen on various immune functions in HIV-1-infected women and uninfected controls. 3) HIV-1 vaccine development. SIV infection in macaques closely resembles human AIDS and represents the best model for assessing the protective efficacy of candidate HIV-1 vaccine. Previously, we demonstrated that immunization with an attenuated recombinant poxvirus vector NYVAC-SIV in combination with a DNA-SIV vaccine candidate expressing the structural genes of SIV resulted in high levels of virus-specific CD4+ and CD8+ T-cell responses and in a significant suppression of viremia following an exposure to the highly pathogenic SIV virus. In addition, we showed a significant improvement following an addition of early/auxiliary genes rev, tat, and nef to the vaccine. Currently, we are developing and testing new vaccine strategies. 4) Design of novel strategies for the immunotherapy of cancer. Immunization of patients with tumor-associated antigens results in the induction of tumor-specific immune responses that can significantly restrict or eliminate the spreading tumor. We are testing the possibility of transplantation with genetically modified hematopoietic stem cells (HSCs) targeting the expression of antigen to activated dendritic cells as a strategy for long-term cancer immunotherapy. In a second project, we investigate immunization with antigen-presenting genetically modified B cells specifically targeted to secondary lymphoid tissue.

Selected Publications  Publication PUBMEDID Huijbregts, R., Helton, S., Michel, K., Richter, H., Goepfert, P., and Z. Hel. 2013. Hormonal contraception and HIV-1 infection: Medroxyprogesterone acetate suppresses the function of T cells and plasmocytoid dendritic cells. Endocrinology. (In print). PMID:23354099.  23354099  Litzman, J., Nechvatalova, J., Xu, J., Ticha, O., Vlkova, M., and Z. Hel. 2012. Chronic immune activation in common variable immunodeficiency (CVID) is associated with elevated plasma levels of soluble CD14 and CD25 but not endotoxemia. Clin. Exp. Immunol. 170:321-332.  23121673  Denning, W., Das, S., Guo, S., Xu, J., Kappes, J., and Z. Hel. 2012. Optimization of the transductional efficiency of lentiviral vectors: effect of sera and polycations. Mol. Biotechnol. 10.1007:s12033.  22407723  Sabbaj, S., Hel, Z., Richter, H., Mestecky, J., and P. A. Goepfert. 2011. Menstrual blood T cells as a potential source of endometrial derived CD3+ cells. PLoS ONE 6:e28894.  22174921  Denning, W., Xu, J., Guo, S., Klug, C., and Z. Hel. 2011. Limited transplantation of antigen-expressing hematopoietic stem cells induces long-lasting cytotoxic T cell responses. PLoS ONE 6:e16897.  21379572  Hel, Z., Stringer, E., and Mestecky, J. 2010. Sex steroid hormones, hormonal contraception and the immunobiology of HIV-1 infection. Endocr. Rev. 31:79-97.  19903932  Mestecky, J., Moldoveanu, Z., Smith, P.D., Hel, Z., Alexander, R.C. 2009. Mucosal immunology of the genital tract and HIV infection. J Reprod. Immunol. 83:186-200.   19853927  Guo, S., Xu, J., Denning, W., and Z. Hel. 2009. Induction of protective cytotoxic T cell responses by a B cell-based cellular vaccine requires stable expression of antigen. Gene Therapy 16:1600-1613.  19641529  Xu,J., Kelly, M., Denning, W., and Hel, Z. 2009. A model for testing the immunogenicity of SIV and SHIV vaccine candidates in mice. J. Virol. Meth. 158:70.   19428572  Hel, Z. Cancer immunization with B cells. 2007. In: Cancer and gene therapy. Ed.: Paul L. Hermonat. Editor: P.L. Hermonat. Research Signposts. 139-153.  18304708  First Prev   1 2 3 of  3  Next Last

Keywords Immunology, HIV-1, Vaccine, Cancer.

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