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Faculty Detail    
Name ZDENEK HEL
PhD
Professor, Tenured		  
Campus Address SHEL 603 Zip 2182
Phone
E-mail  zhel@uab.edu
Other websites https://sites.uab.edu/zdenek-hel-lab/
     

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  Joint Pathology  Molecular & Cellular Pathology Professor
Secondary  Microbiology  Microbiology Professor
Center  Center for AIDS Research  Center for AIDS Research Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor
Center  Sparkman Ctr for Global Health  Sparkman Ctr for Global Health Professor
Center  UAB Immunology Institute  UAB Immunology Institute Professor

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

Biographical Sketch 
2017-present Professor, Department of Pathology, Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA. 2011-2017 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/ 
American Association of Immunologists    http://www.aai.org/ 
Czech Immunological Society    http://www.biomed.cas.cz/cis/en/ 
International AIDS Society    http://www.ias.se/ 
 



Research/Clinical Interest
Title
Immunology and pathogenesis of HIV-1 / AIDS; Neutrophil biology; Effect of hormonal contraception on immune system; Design of novel strategies for immunotherapy of cancer; Covid-19.
Description
Research in our laboratory focuses on the following areas: 1) The multifaceted role of neutrophils in HIV-1-infection. In recent years, a new appreciation of the role of neutrophils in regulating the immune system has emerged. Neutrophils are the most abundant leukocyte population and are traditionally recognized as essential effector cells of the innate immune system in the host defense against invading organisms. While neutrophils have been shown to play important roles in viral pathogenesis, a knowledge gap exists in our understanding of the function of neutrophils in individuals infected with human immunodeficiency virus-1 (HIV-1). The data recently accumulated in our laboratory reveals the multifaceted role of neutrophils in HIV-1-infection where they exert both pro-inflammatory and anti-inflammatory effects. We demonstrated that chronic HIV-1-infection and ongoing microbial translocation is associated with the induction of neutrophils with immunosuppressive activity that significantly contribute to the suppression of T cell function in HIV-1-infection. In addition, we show that enhanced neutrophil extracellular trap (NET) formation in HIV-1-infected subjects may contribute to the incidence of inflammatory-driven disease through direct effects of NETs or indirectly through NET mediated effects on macrophage function. These findings show that the role of neutrophils in HIV-1-infection is more complex than previously recognized. 2) Mucosal antibody production and the 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. 3) 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. 4) 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. 5) 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
Ong, K.L, Davis, M.D., Purnell, K.K., Cutshall, H., Pal, H.C., Connelly, A.N., Fay, C.X., Kuznetsova, V., Brown, E.E., and Z. Hel. Distinct phenotype of neutrophil, monocyte, and eosinophil populations indicates altered myelopoiesis in a subset of patients with multiple myeloma. Frontiers in Oncology. 2023. 12:1074779.   36733370 
Connelly, A.N., Huijbregts, R.P.H., Pal, H.C., Kuznetsova, V., Davis. M.D., Ong, K.L., Fay, C.X., Greene, M.E., Overton, E.E., and Z. Hel. Optimization of methods for the accurate characterization of whole blood neutrophils. Scientific Reports. 2022. 12:3667.  35256648 
Lazarus JV, Romero D, Kopka CJ, Karim SA, Abu-Raddad LJ, Almeida G, Baptista-Leite R, Barocas JA, et al. A multinational Delphi consensus to end the COVID-19 public health threat. 2022. Nature. 611:332-345.   36329272 
Valdez, A.C., Iftekhar, E.N., Oliu-Barton, M., Hel, Z., et al. Europe must come together to confront Omicron. 2022. BMJ. 376:o90.   35027352 
Priesemann, V., Balling, R., Brinkmann, M.M., Ciesek, S., Czypionka, T., Eckerle, I., Giordano, G., Hanson, C., Hel, Z., Hotulainen, P., Klimek, P., Nassehi, A., Peichl, A., Perc, M., Petelos, E., Prainsack, B., Szczurek,E. 2021. An action plan for pan-European defence against new SARS-CoV-2 variants. 2021. The Lancet. 397 (10273): 469-470.
 		 33485462 
Jimenez, R.V., Kuznetsova, V., Connelly, A., Hel, Z., Szalai, A.J. 2019. C-reactive protein promotes the expansion of myeloid-derived cells with a suppressor phenotype. Front. Immunol. 10:2183.
 		 31620123 
Litzman, J., Chovancova, Z., Bejdak, P., Litzman, M., Hel, Z., and M. Vlkova. 2019. Common variable immunodeficiency (CVID) patients display elevated plasma levels of granulocyte activation markers elastase and myeloperoxidase. Int. J. Immunopathol. Pharmacol. 33.
 		 30968712  
Vlkova M., Chovancova, Z., Nechvatalova J., Connely, A.N., Davis, M.D., Slanina, P. Travnickova L., Litzman M., Freiberger T., Litzman J., and Z. Hel. 2019. Neutrophil and granulocytic myeloid-derived suppressor cell (G-MDSC)-mediated immune suppression in common variable immunodeficiency disorders (CVID). J. Immunol. 202: 93-104.
 		 30487174  
Hapgood, J.P., Kaushic, C., and Z. Hel. 2018. Hormonal Contraception and HIV-1 Acquisition: Biological Mechanisms. Endocrine Reviews. 39:36-78.   29309550 
Polis, C.B., Achilles, S.L., Hel, Z., Hapgood, J.P. 2018. Is a lower-dose, subcutaneous contraceptive injectable containing depot medroxyprogesterone acetate likely to impact women’s risk of HIV? Contraception. 97:191-197.  29242082 
Hel, Z., Xu, J., Denning. W., Helton, S., Heath, S. L., Christmann, B.S., Elson, C.O., Goepfert, P., and Mestecky, J. 2017. Dysregulation of systemic and mucosal humoral responses to microbial and food antigens as a factor contributing to microbial translocation and chronic inflammation in HIV-1 infection. PLOS Pathogens. 13:e1006087  28125732  
Michel, K.G., Huijbregts, R.P.H., Gleason, J.L., Richter, H., E., and Z. Hel. 2015. Effect of hormonal contraception on the function of plasmacytoid dendritic cells and distribution of immune cell populations in the female reproductive tract. JAIDS. 68:511-518.  25763784 
Hel, Z., Huijbregts, R.P., Xu, J., Nechvatalova, J., Vlkova, M., and J. Litzman. 2014. Altered serum cytokine signature in common variable immunodeficiency. J. Clin. Immunol. 34:971-8.   25246148 
Bowers, N., Helton, S., Huijbregts, R.P.H., Goepfert, P., Heath, S., and Z. Hel. 2014. Neutrophils in HIV-1-infected individuals express high levels of PD-L1 and exert immunosuppressive activity. PLOS Pathogens. 10 :e1003993.  24626392 
Huijbregts, R.P.H., Michel, G., and Z. Hel. 2014. Effect of progestins on immunity: medroxyprogesterone but not norethisterone or levonorgestrel suppresses the function of T cells and pDCs. Contraception. 90:123-129.  24674041 
Gupta, S., Gach, J.S., Becerra, J.C., Phan, T.B., Pudney, J., Moldoveanu, Z., Joseph, S.B., Landucci, G., Supnet, M.J., Ping, L. Corti, D., Moldt, B., Hel, Z., Lanzavecchia, A., Ruprecht, R.M., Burton, D.R., Mestecky, J., Anderson, D.J, and Forthal, D.N. 2013. The neonatal Fc receptor (FcRn) enhances human immunodefiency virus type 1 (HIV-1) transcytosis across epithelial cells. PLOS Pathogens. 9:e1003776.  24278022 
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.154:1282-1295. 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 
Raska, M., Moldoveanu, Z., Novak, J., Hel, Z., Bozja, J., Compans, R.W., Yang, C., and J. Mestecky. 2008. Delivery of DNA HIV-1 vaccine to the liver induces high and long-lasting humoral immune responses. Vaccine 26:1541.  18304708 
Hel, Z., McGhee, J., Mestecky, J. 2006. HIV infection: First battle decides the war. Trends Immunol. 27: 274-281.  16679064 
Pal, R., Venzon, D., Santra, S., Kalyanaraman, V.S., Montefiori, D.C., Hocker, L., Hudacik,
L., Rose, N., Nacsa, J., Edghill-Smith, Y., Moniuszko, M., Hel, Z., Belyakov, I.M.,Berzofsky, J.A., Washington-Parks, R., Markham, P.D., Letvin, N.L., Tartaglia, J., and G. Franchini. 2006. Systemic immunization with an ALVAC-HIV-1 / protein boost vaccine strategy protects rhesus macaques from CD4+ T cell loss and reduces both systemic and mucosal SHIVKU2 RNA levels. J. Virol. 80:3732.
 		 16571790 
Hel, Z., Tsai, W.-P., Tryniszewska, E., Nacsa, J., Markham, P.D., Lewis, M.G., Pavlakis, G.N., Felber, B.K., Tartaglia, J., and Franchini, G. 2006. Improved vaccine protection from simian AIDS by the addition of nonstructural SIV genes. J. Immunol. 176:85-96.  16365399 
Hel, Z., Nacsa, J., Tsai, W.P., Thornton, A., Giuliani, L., Tartaglia, J., and G. Franchini. 2002. Equivalent immunogenicity of the highly attenuated poxvirus-based ALVAC-SIV and NYVAC-SIV vaccine candidates in SIVmac251-infected macaques. Virology 304:125-134.  12490410 
Hel, Z., Tryniszewska, E., Johnson, J.M., Harrod, R., Fullen, J., Kalyanaraman, V.S., Altman, J.D., McNally, J., Kaprova, T., Felber, B.K., Tartaglia, J., and G. Franchini. 2002. Design and in vivo immunogenicity of a polyvalent vaccine based on SIVmac regulatory genes. DNA Cell. Biol. 21:619-626.  12396604 
Hel, Z. Nacsa,J., Tryniszewska, E., Tsai, W.P., Washington-Parks, R., Montefiori, D.C., Felber, B.K., Pavlakis, G.N., Tartaglia,ƒnJ., and G. Franchini. 2002. Containment of SIV infection in vaccinated macaques: Correlation with the magnitude of virus-specific pre- and post-challenge CD4+ and CD8+ T-cell responses. J. Immunol. 169:4778-4787.  12391187 
Hel, Z., Johnson, J.M., Tryniszewska, E., Tsai, W.P., Harrod, R., Fullen, J., Tartaglia, J., and G. Franchini. 2002. A novel chimeric Rev, Tat, and Nef (Retanef) antigen as a component of an SIV/HIV vaccine. Vaccine 20:3171-3186.  12163269 
Hel, Z., Tsai, W.P., Thornton, A., Nacsa, J., Giuliani, L., Tryniszewska, E., Poudyal, M., Venzon, D., Wang, X., Altman, J., Watkins, D.I., Lu, W., von Gegerfelt, A., Felber, B.K., Tartaglia, J., Pavlakis, G.N., and G. Franchini. 2001. Potentiation of Simian immunodeficiency virus (SIV)-specific CD4(+) and CD8(+) T cell responses by a DNA-SIV and NYVAC-SIV prime/boost regimen. J. Immunol. 167: 7180-7191.  11739541 
Belyakov, I.M., Hel, Z., Kelsall, B., Kuznetsov, V.A., Ahlers, J.D., Nacsa, J., Watkins, D.I., Allen, T.M., Sette, A., Altman, J., Woodward, R., Markham, P.D., Clements, J.D., Franchini, G., Strober, W., and J. A. Berzofsky. 2001. Mucosal AIDS vaccine reduces disease and viral load in gut reservoir and blood after mucosal infection of macaques. Nature Med. 7:1320-6.  11726972 
Hel, Z., Nacsa, J., Kelsall, B., Tsai, W.P., Letvin, N., Parks, R.W., Tryniszewska, E., Picker, L., Lewis, M.G., Edghill-Smith, Y., Moniuszko, M., Pal, R., Stevceva, L., Altman, J.D., Allen, T.M., Watkins, D., Torres, J.V., Berzofsky, J.A., Belyakov, I.M., Strober, W., and G. Franchini. 2001. Impairment of Gag-Specific CD8(+) T-Cell function in mucosal and systemic compartments of Simian immunodeficiency virus mac251- and Simian-human immunodeficiency virus KU2-infected macaques. J. Virol. 75:11483-95.  11689630 
Hel, Z., Venzon,D., Poudyal, M., Tsai, W.P., Giuliani, L., Woodward, R., Chougnet, C., Shearer, G., Altman, J., Watkins,D., Bischofberger, N., Abimuku, A., Markham, P., Tattaglia, J., and Franchini, G. 2000. Viremia control following structured treatment interruption and therapeutic immunization of SIV251 -infected macaques. Nature Med. 6:1140-6.  11017146 
 

Keywords
Immunology, Neutrophils, HIV-1, Vaccine, Cancer, Covid-19.