Marcelo B Sztein
 

Marcelo B Sztein M.D.

Academic Title: Professor
Primary Appointment: Pediatrics
Secondary Appointments: Microbiology and Immunology
msztein@medicine.umaryland.edu
Location: HSF1 480
Phone: (410) 706-2345
Fax: (410) 706-6205

Personal History

Dr. Sztein received an M.D. degree from the School of Medicine, University of Buenos Aires, Argentina, in 1976.  He did his post-doctoral fellowship at NIH with Dr. Joe Oppenheim before becoming a faculty member, first at George Washington University and then at the University of Maryland.

Dr. Sztein joined the Center for Vaccine Development (CVD) in 1989 as Chief of the Cellular Immunology and Flow Cytometry Section. Under Dr. Sztein’s leadership, the Immunology Group at the CVD, which he leads, has expanded dramatically. The CVD’s Immunology Group currently consists of approximately 20 individuals, including faculty, laboratory supervisors and other technical personnel, post-doctoral fellows and students.

Dr. Sztein is an accomplished investigator in the area of immunology of infectious diseases. As author and/or co-author of 134 peer-reviewed scientific articles and over 30 chapters and Meeting reports, Dr. Sztein is a recognized authority in the human host systemic and mucosal immune response to vaccination and the identification of immunological mechanisms of protection from infection in human and animal models, particularly in the area of enteric diseases.

Dr. Sztein has a consistent record of grant support from the NIH, industry and other agencies since 1983 and is a Standing Member of the Microbiology and Infectious Diseases Research Committee (MIDRC), Microbiology, Infectious Diseases and AIDS Initial Review Group, National Institute of Allergy and Infectious Diseases, NIH (the study section responsible for reviewing K08, K22, K23, K24, K25, K99/R00, T32 and T35 applications).  Moreover, he participates regularly as ad-hoc member in other Grant Review Panels of the National Institutes of Health, holds membership in numerous scientific societies, is actively involved in the organization of the National/International meetings and serves as reviewer in major peer-reviewed research journals.

Research Interests

Basic and translational models of infectious diseases, chiefly in the areas of vaccine development and host-pathogen interactions, are used in Dr. Sztein's laboratory to uncover the mechanisms underlying protective innate, cellular and antibody immune responses in volunteers and animals.

Current projects encompass studies to investigate systemic and mucosal innate and adaptive immune responses in volunteers participating in vaccine trials being conducted at the CVD and other sites, including underdeveloped countries. These trials involve the clinical testing of genetically engineered attenuated vaccine strains developed at the CVD and other institutions, such as attenuated Salmonella enterica serovar Typhi and Shigella (alone or as carriers of foreign genes). Immunological studies in other infectious diseases, including malaria, hepatitis B, influenza and tularemia, are also being performed in immunized or naturally exposed subjects and in animal models. These investigations involve microorganisms relevant to bio-defense. The broad goal of these studies is to uncover the immune mechanisms of protection against infectious agents with the long-term goal of accelerating the development of effective vaccines.

Dr. Sztein's group has also been involved for over two decades in studies directed to unveil the mechanisms that might underlie the immunosuppression observed in patients with various infectious diseases and the mechanisms underlying decreased immunity to vaccination in elderly volunteers. Moreover, Dr. Sztein has participated for many years in international collaborative studies and is deeply committed to the training of investigators in underdeveloped nations. In this context, he has directed the establishment of a state-of-the-art immunology laboratory (that includes flow cytometry capabilities) at the University of Mali, Bamako and an immunology lab at the Bandiagara field site in Mali, West Africa, to study the immune responses of volunteers in malaria endemic areas.

State-of-the-art technologies (e.g., multichromatic flow cytometric analysis and sorting, ELISPOT, DNA microarrays) are being used in Dr. Sztein’s laboratories to study immune responses in animal models and humans, including cytokine production and receptor expression, biochemical pathways of lymphocyte activation, lymphoproliferative responses and cytotoxic T cell activity.

Laboratory Personnel:

CVD Cellular Immunology Section and Flow Cytometry Core Laboratory

• Rosangela Salerno-Mezghanni, Ph.D. Instructor
• Jakub Simon, M.D. Assistant Professor
• M. Rezwanul Wahid, M.D., Ph.D. Research Associate
• Abdul Khan, Ph.D. Post-doctoral Fellow  
• Milton Maciel, Ph.D. Post-doctoral Fellow
• Regina Harley, M.S. Research Specialist
• Cathy Storrer, B.S. Research Specialist
• Jeffrey Floyd, B.S. Research Assistant
• Guillermo Sahaniuk, M.S. Research Assistant
• Meagan Fitzpatrick, B.S. Research Assistant


Job Openings:

Positions are available for postdoctoral fellows and graduate students wishing to join a multidisciplinary group that focuses on basic and translational studies in several models of infectious diseases directed to uncover the mechanisms underlying protective innate, cellular and antibody immune responses to a variety of microorganisms in volunteers and animals, chiefly in the areas of vaccine development and host-pathogen interactions.

Studies include working with specimens obtained from adults and elderly subjects immunized with genetically engineered strains of Salmonella enterica serovar Typhi and Shigella vaccine candidates, as well as immunized with malaria, hepatitis B, influenza and tularemia vaccines.  Areas of study include antigen presentation, MHC-restriction, cloning and characterization of cytotoxic and helper T cells, identification of protective epitopes, role of dendritic and regulatory T cells, microarray profiling and manipulation of cytokine production patterns to elucidate their role in the induction of innate, systemic and mucosal immune responses to vaccination and the mechanisms of immunosenescence. 

The Center for Vaccine Development (CVD) offers a unique environment to study cellular and molecular determinants of protection to infectious diseases in humans. The CVD, largely supported by NIH funding and private foundations, has earned an international reputation for genetically engineering and testing vaccines against typhoid, shigella, cholera and malaria. Based at the School of Medicine, University of Maryland, Baltimore, the CVD was established in the mid-1970s as one of the first facilities to evaluate vaccines in community volunteers.  It is one of only a handful of vaccine centers in the world engaged in the full range of vaccinology - from basic science through vaccine development, immunological studies, clinical evaluation and field studies. Contact Dr. Marcelo Sztein for additional information.



Publications

Peer-Reviewed Journals (Last 5 years)

Pasetti, M.F., Cuberos, L., Horn, T.L., Shearer, J.D., Matthews, S.J., House, R.V. and Sztein, M.B. An improved Francisella tularensis Live Vaccine Strain (LVS) formulation is well tolerated and highly immunogenic when administered to rabbits in escalating doses using various immunization routes. Vaccine. (In press.) 2008

Rallabhandi, P., Awomoyi, A., Thomas, K.E., Phalipon, A., Fujimoto, Y., Fukase, K., Kusumoto, S., Qureshi, N., Sztein, M.B. and Vogel, S.N. Differential Activation of Human TLR4 by E. coli and S. flexneri 2a Lipopolysaccharide: Effect of Lipid A Acylation State and TLR4 Polymorphisms on Signaling. J. Immunol. 180: 1139–1147, 2008.

Kotloff, K.L., Simon, J.K., Pasetti, M.F., Sztein, M.B., Wooden, S.L., Livio, S., Nataro, J.P., Blackwelder, W.C., Barry, E.M., Picking, W. and Levine, M.M.  Safety and Immunogenicity of CVD 1208S, a live, oral ΔguaBA, Δsen, Δset Shigella flexneri 2a vaccine grown on animal-free media. Human Vaccines 3: 268-275, 2007.

Awomoyi, A.A., Rallabhandi, P., Pollin, T.I., Lorenz, E., Sztein, M.B., Boukhvalova, M.S., Hemming, V.G., Blanco, J.C. and Vogel, S.N. Association of TLR4 Polymorphisms with Symptomatic Respiratory Syncytial Virus Infection in High-Risk Infants and Young Children. J. Immunol. 179: 3171-3177, 2007.

Sztein, M.B.  Cell-mediated immunity and antibody responses elicited by attenuated S. Typhi strains used as live oral vaccines. Clin. Inf. Dis.  45(S1):S15-S19, 2007.

Levine, M.M., Kotloff, K.L., Barry, E.M., Pasetti, M.F. and Sztein, M.B. Clinical trials of Shigella Vaccines: Two Steps Forward and One Step Back on a Long, Hard Road.  Nature Reviews Microbiol. 5: 540-553, 2007.

Wahid, R., Salerno-Gonçalves, R., Tacket, C.O., Levine, M.M. and Sztein, M.B. Cell-mediated immune responses in humans after immunization with one and two doses of oral live attenuated typhoid vaccine CVD 909. Vaccine. 25: 1416-1425, 2007.

Salerno-Gonçalves, R. and Sztein, M.B. Cell-mediated immunity and the challenges for vaccine development. Trends in Microbiology. 14: 536-542, 2006.

Lyke, K.E., Dabo, A., Sangare, L., Arama, C., Dao, M., Diarra, I., Plowe, C.V., Doumbo, O.K. and Sztein, M.B. Effects of concomitant Schistosoma haematobium infection on the serum cytokine levels elicited by acute Plasmodium falciparum malaria infection in Malian children. Infect. Immun. 74: 5718-5724, 2006.

Cissoko, Y., Daou, M., Lyke, K.E., Dicko, A., Diarra, I., Kone, A., Guindo, A., Traore, K., Krishnegowda, G., Diallo, D.A., Doumbo, O.K., Plowe, C.V., Gowda, D.C. and Sztein, M.B. Serum Antibody Levels to Glycosylphosphatidylinositols (GPIs) in Specimens Derived from Matched Malian Children with Severe or Uncomplicated Plasmodium Falciparum Malaria and Healthy Controls. Am. J. Trop. Med. Hyg.  75: 199-204, 2006.

Lyke, K.E., Dicko, A., Dabo, A., Sangare, L. Kone, A., Coulibaly, D., Guindo, A., Traore, K., Dra, M., Diarra, I., Sztein, M.B., Plowe, C.V. and Doumbo, O.K. Association of Schistosoma haematobium Infection with Protection Against Acute Plasmodium falciparum Malaria in Malian Children. Am. J. Trop. Med. Hyg. 73: 1124-1130, 2005.

Lyke, K.E., Burges,R.B., Cissoko, Y., Sangare, L., Kone, A. Dao, M., Diarra, I.,  Fernández-Vina, M.A., Plowe, C.V., Doumbo, O.K. and Sztein, M.B. HLA-A2 Supertype-restricted Cell-mediated Immunity by Peripheral Blood Mononuclear Cells Derived from Malian Children with Severe or Uncomplicated P. falciparum Malaria and Healthy Controls. Infect. Immun. 73: 5799-5808, 2005.

Salerno-Gonçalves, R., Wahid, R. and Sztein, M.B. Immunization of Volunteers with Salmonella enterica serovar Typhi Strain Ty21a Elicits the Oligoclonal Expansion of CD8+ T Cells with Predominant V¿ Repertoires. Infect. Immun. 73: 3521-3530, 2005.

Salerno-Gonçalves, R., Fernandez-Viña, M., Lewinsohn, D.M. and Sztein, M.B. Identification of a Human HLA-E-Restricted CD8+ T cell Subset in Volunteers Immunized with Salmonella enterica serovar Typhi Strain Ty21a Typhoid Vaccine. J. Immunol. 173: 5852-5862, 2004.

Lyke, K.E., Burges, R., Cissoko, Y., Sangare, L., Dao, M., Diarra, I., Kone, A., Harley, R., Plowe, C.V., Doumbo, O.K. and Sztein, M.B. Serum Levels of Pro-inflammatory Cytokines Interleukin-1 beta, IL-6, IL-8, IL-10, Tumor Necrosis Factor-alpha and IL-12p70 in Malian Children with Severe Plasmodium falciparum Malaria and Matched Uncomplicated Malaria or Healthy Controls. Infect. Immun. 72: 5630-5637, 2004.

Levine, M.M. and Sztein, M.B. Vaccine Development Strategies for Improving Immunization: The Role of Modern Immunology. Nat. Immunol. 5: 460-464, 2004. Commentary.

Kotloff, K.L. Pasetti, M.F., Barry, E.M., Nataro, J.P., Wasserman, S.S., Sztein, M.B., Picking, W.D. and Levine, M.M.  Deletion in the Shigella Enterotoxin Genes Further Attenuates Shigella flexneri 2a Bearing Guanine Auxotrophy in a Phase 1 Trial of CVD 1204 and CVD 1208.  J. Infect. Dis. 190: 1745-1754, 2004.

Tacket, C.O., Pasetti, M.F., Sztein, M.B., Livio, S. and Levine, M.M. Immune Responses to an Oral Typhoid Vaccine Strain Modified to Constitutively Express Vi Capsular Polysaccharide. J. Infect. Dis. 190: 565-570, 2004.

Cao, K., Moormann, A.M., Lyke, K.E., Masaberg, C., Sumba, O.P., Doumbo, O.K., Koech, D., Lancaster, A., Nelson, M., Meyer, D., Single, R., Hartzman, R.J., Plowe, C.V., Kazura, J., Mann, D.L., Sztein, M.B., Thomson, G. and Fernández-Viña, M.A. Differentiation Between African Populations is Evidenced by the Diversity of Alleles and Haplotypes of HLA class I Loci. Tissue Antigens.  63: 293-325, 2004.

Tacket, C.O., Sztein, M.B., Losonsky, G.A., Wasserman, S.S. and Estes, M.K.  Humoral, Mucosal and Cellular Immune Responses to Oral Norwalk virus-like Particles (VLP) in Volunteers.  Clin. Immunol.  108: 241-247, 2003.

Pasetti, M.F., Barry, E.M.,  Losonsky, G., Singh, M., Medina-Moreno, S.M., Polo, J.M., Ulmer, J., Robinson, H., Sztein, M.B. and Levine, M.M. Attenuated Salmonella enterica serovar Typhi and Shigella Flexneri 2a Strains Mucosally Deliver DNA Vaccines Encoding Measles Virus Hemagglutinin, Inducing Specific Immune Responses and Protection in Cotton Rats.  J. Virology.  77: 5209-5217, 2003.

Salerno-Gonçalves, R., Wyant, T.L., Pasetti, M.F., Fernandez-Viña, M., Tacket, C.O., Levine, M.M. and Sztein, M.B.  Concomitant Induction of CD4+ and CD8+ T Cell Responses in Volunteers Immunized with Salmonella enterica serovar Typhi Strain CVD 908htrA. J. Immunol.  170: 2734-2741, 2003. 

Rosenkranz, C.D., Chiara, D., Agorio, C., Baz, A., Pasetti, M.F.,  Schreiber, F., Dematteis, S.,  Martinez, M., Sztein, M.B. and Chabalgoity, J.A.  Towards New Immunotherapies: Targeting Recombinant Cytokines to the Immune System using Live Attenuated Salmonella. Vaccine.  21: 798-801, 2003.

Pasetti, M.F., Levine, M.M. and Sztein, M.B.  Animal Models Paving the Way for Clinical Trials of Attenuated Salmonella Typhi Live Oral Vaccines and Live Vectors.  Vaccine.  21: 401-418, 2003.

Kierszenbaum, F., Fresno, M. and Sztein, M.B.  The Trypanosomal  Membrane Glycoprotein AGC 10 Inhibits Division of Activated Human Lymphocytes by a Mechanism Involving Decreased Biosynthesis of IL-2 and High-affinity IL-2 Receptor Components.  Molec. Biochem. Parasitol.  125: 91-101, 2002.

Salerno-Gonçalves, R., Pasetti, M.F. and Sztein, M.B. Characterization of CD8+ Effector T Cell Responses in Volunteers Immunized with Salmonella enterica serovar Typhi Strain Ty21a Typhoid Vaccine.  J. Immunol.  169: 2196-2203, 2002.

Pasetti, M.F., Salerno-Gonçalves, R. and Sztein, M.B. Salmonella enterica serovar Typhi Live Vector Vaccines Delivered Intranasally Elicit Regional and Systemic Specific CD8+ MHC Class I-restricted Cytotoxic T Lymphocytes.  Infect. Immun.   70: 4009-4018, 2002.

Kotloff, K.L., Taylor, D.N., Sztein, M.B., Wasserman, S.S., Losonsky, G.A., Nataro, J.P., Venkatesan, M., Hartman, A., Picking, W.D., Katz, D.E., Campbell, J.D., Levine, M.M. and Hale, T.L.   Phase I Evaluation of a virG Deleted Shigella sonnei Live, Attenuated, Oral Vaccine Strain WRSS1 in Healthy Adults.  Infect. Immun.  70: 2016-2021, 2002




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