Susan Zolla-Pazner, PhD Email Susan Zolla-Pazner
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- Positions
- PROFESSOR | Medicine, Infectious Diseases
- PROFESSOR | Microbiology
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- Language
- English
Dr. Zolla-Pazner received her Bachelor’s degree at Stanford University and her Ph. D. in Medical Microbiology at the University of California Medical Center in San Francisco. Her doctoral studies were focused on the immunochemistry of antibodies produced by immunization, and were a continuation of the pioneering immunochemical studies of Dr. Michael Heidelberger and Dr. Elvin Kabat. Her research made use of the sera employed for passive immunization in the treatment of pneumococcal pneumonia prior to the advent of antibiotic treatment. Dr. Zolla-Pazner’s Ph. D dissertation focused on the cross-reactivity of anti-pneumococcal antibodies and the unusual isotype of antibodies present in the horse sera used for treatment of pneumonia. Having completed her doctoral training, Dr. Zolla-Pazner spent two years as a post-doctoral fellow at the NYU School of Medicine working with Dr. Edward C. Franklin. While a fellow at NYU, Dr. Zolla-Pazner’s research focused on immunoglobulin synthesis by myeloma cells derived from human bone marrow biopsies. These studies led to several years of study of mouse plasmacytomas and their suppressive effects on induction of antibody responses. These early studies established her credentials as “a B cell immunologist”.
In 1969, Dr. Zolla-Pazner established her own laboratory at the New York Veterans Administration Hospital in Manhattan, which was and is a part of the NYU Medical Center. There, she continued her work on mouse plasmacytomas and, in 1977 she also became the Director of the Clinical Immunology Laboratory, the only lab in the NYU/VA complex to assess the function of immune responses in human patients. As a result of her Directorship of the Human Clinical Immunology lab, in 1981 Dr. Zolla-Pazner was among the first scientists to participate in the description of the immunologic abnormalities in patients with the then mysterious illness which became known as AIDS, affecting gay men, hemophiliacs and intravenous drug users. She was also responsible for providing the initial descriptions of immunologic abnormalities for the first patients with AIDS-related Mycobacterium avium-intracellulare and to identify similar immunologic abnormalities in apparently healthy gay men who went on to develop AIDS. This work established the chilling realization that 1/3 of gay men in New York City were suffering from a potentially fatal unknown illness.
In these early days of the AIDS epidemic, the Zolla-Pazner lab described the hyperactivation of B lymphocytes in HIV-infected individuals, and this discovery led Dr. Zolla-Pazner to develop methods allowing the generation of anti-HIV human monoclonal antibodies (mAbs) from the cells of HIV-infected individuals. Her lab was among the first to isolate and describe human mAbs capable of neutralizing the infectivity of the virus, and later was the first lab to isolate a mAb ofgreat neutralizing potency targeting a quaternary neutralizing epitope which includes the V2 loop of the HIV envelope protein. Studies of the second and third variable loops (V2 and V3 loops) of the gp120 envelope protein contributed to an understanding of their function in virus infectivity as well as how and why V2 and V3 from diverse viruses share antigenic similarities.
Using the mAbs described above, Dr. Zolla-Pazner and her colleagues have identified generic, shared structures in the V2 and V3 loops and used these to design V2- and V3-scaffold protein immunogens. Her lab has also used gp120 DNA as a priming immunogen, and recombinant “designer epitope-scaffold immunogens” to show that the immune response in rabbits and non-human primates can be focused on a single envelope epitope (V2 or V3), thus inducing antibodies which recognize diverse strains and subtypes of the virus; these antibodies have the potential of blocking infection by HIV. This body of work led to the seminal finding of the correlation between antibodies directed at the V2 loop of gp120 and the reduced risk of infection in the RV144 clinical vaccine trial, a finding that has been pivotal in establishing the central role of antibodies in protection from HIV infection and has helped to focus the HIV vaccine field on humoral immunity in preventing HIV infection. This platform for immunogen design is now being applied to the development of V2-scaffold immunogens on the basis of crystallographic studies of V2 mAbs and the V2 epitopes they target.
At Mount Sinai School of Medicine, Dr. Zolla-Pazner’s research continues to focus on the immunologic abnormalities in HIV infection and the development of HIV vaccine candidates. Specifically the Zolla-Pazner lab studies the production and characterization of human anti-HIV mAbs, the epitopes they target, and the immunologic and biologic properties of the variable regions of the HIV gp120 envelope glycoprotein. This information is being used to develop a prophylactic HIV vaccine.
Since beginning her independent research in 1969, Dr. Zolla-Pazner has received continuous funding and served as Principle Investigator on research grants, program project grants and training grants from the NIH, Department of Veterans Affairs, US Army, and the Bill and Melinda Gates Foundation. Dr. Zolla-Pazner has published over 300 papers, many in high impact journals including Science, Journal of Infectious Diseases, Journal of Immunology, Journal of Virology, Nature Structural and Molecular Biology, and the New England Journal of Medicine. She is an elected fellow of the American Association for the Advancement of Science (AAAS) and the American Society of Microbiology (ASM), and Adjunct Professor at the Rockefeller University.
Research Topics
Antibody Development, B Cells, Biomedical Sciences, HIV/AIDS, Immune Deficiency, Immunoglobulin Genes, Infectious Disease, Lymphocytes, Macrophage, Protein Structure/Function, Retrovirus, Structural Biology, Viruses and Virology
Multi-Disciplinary Training Areas
Immunology [IMM], Microbiology [MIC]
Language
English
2015
Elected Fellow
American Society of Microbiology
2011
Elected Fellow
American Association for the Advancement of Science
2010
Member, RV144 HIV Clinical Vaccine Trials Committee on Humoral/Innate Immunity
2008
Member, Scientific Advisory Board for M. Cho (University of Iowa Medical School) HIVRAD Program Project Grant
2008
Member, Scientific Advisory Board for R. Ruprecht (Dana-Farber Institute, Harvard Medical School) HIVRAD Program Project Grant
2003
Pioneer Lecturer: Immunology of AIDS, Keystone Conference
2003
Member
AIDS Research Review Study Section, NIAID
1994
Member
Advisory Group for Vaccine Issues & Objectives, NIH Office of AIDS Research
1994
US Chair, AIDS Panel, U.S.- Japan Cooperative Medical Science Program, NIH
1992
Member
AIDS Research Advisory Comittee (ARAC), NIAID/NIH
1992
Member
Vaccine Working Group, DAIDS, NIAID, NIH
1990
Sustained Superior Performance Awards
Veterans Administration
1988
Member
National Institutes of Health (NIH) Special Study Section on AIDS
1985
Superior Performance Awards
Department of Veterans Affairs
1983
Chairman of the First and Second Workshops on AIDS at the Fifth & Sixth International Congresses of Immunology
1982
Co-author of two of the 100 most frequently cited papers published in 1982
NYU School of Medicine Dean's Incentive Awards
2002, 2004, 2005, 2009
AIDS/HIV, Antigen Presentation, B Cells, Computer Simulation, Crystallography, Immune Deficiency, Immunoglobulin Genes, Immunology, Immunosuppression, Infectious Disease, Lymphocytes, Macrophage, Molecular Biology, Protein Structure/Function, Structu
The Zolla-Pazner laboratory is focused on the development of an HIV vaccine through studies of the antibodies (Abs) made by HIV-infected individuals and immunized animals. Together with colleagues participating in a large NIH-sponsored program grant, human monoclonal antibodies (mAbs) that target the envelope glycoproteins of HIV are produced from the peripheral blood cells of infected subjects; these mAbs are characterized for their immunochemical features and their anti-viral functions. The mAbs of interest are crystallized and the nature of the antigenic determinants (epitopes) they recognize are determined. These epitopes serve as templates for the design of recombinant “designer immunogens” which are being tested as candidate HIV vaccines in rabbits and monkeys. The Ab response of the immunized animals is analyzed to determine if the Abs made by the animal resemble the mAbs used at the beginning of this process, and if the immune sera from the animals have anti-viral (protective) activity in vitro and in vivo. These studies are augmented by an on-going interest in the protective role of different immunoglobulin classes against HIV and in improved methods for inducing more potent and durable Ab responses by vaccination. The Zolla-Pazner laboratory is focused on the development of an HIV vaccine through studies of the antibodies (Abs) made by HIV-infected individuals and immunized animals. Together with colleagues participating in a large NIH-sponsored program grant, human monoclonal antibodies (mAbs) that target the envelope glycoproteins of HIV are produced from the peripheral blood cells of infected subjects; these mAbs are characterized for their immunochemical features and their anti-viral functions. The mAbs of interest are crystallized and the nature of the antigenic determinants (epitopes) they recognize are determined. These epitopes serve as templates for the design of recombinant “designer immunogens” which are being tested as candidate HIV vaccines in rabbits and monkeys. The Ab response of the immunized animals is analyzed to determine if the Abs made by the animal resemble the mAbs used at the beginning of this process, and if the immune sera from the animals have anti-viral (protective) activity in vitro and in vivo. These studies are augmented by an on-going interest in the protective role of different immunoglobulin classes against HIV and in improved methods for inducing more potent and durable Ab responses by vaccination.
Mayr LM, Cohen S, Spurrier B, Kong XP, Zolla-Pazner S. Epitope mapping of conformational V2-specific anti-HIV human monoclonal antibodies reveals an immunodominant site in V2. PloS one 2013; 8(7).
Zolla-Pazner S. Saving specimens after Sandy. The New England journal of medicine 2013 May; 368(21).
Zolla-Pazner S, deCamp AC, Cardozo T, Karasavvas N, Gottardo R, Williams C, Morris DE, Tomaras G, Rao M, Billings E, Berman P, Shen X, Andrews C, O'Connell RJ, Ngauy V, Nitayaphan S, de Souza M, Korber B, Koup R, Bailer RT, Mascola JR, Pinter A, Montefiori D, Haynes BF, Robb ML, Rerks-Ngarm S, Michael NL, Gilbert PB, Kim JH. Analysis of V2 antibody responses induced in vaccinees in the ALVAC/AIDSVAX HIV-1 vaccine efficacy trial. PloS one 2013; 8(1).
Chung AW, Crispin M, Pritchard L, Robinson H, Gorny MK, Yu X, Bailey-Kellogg C, Ackerman ME, Scanlan C, Zolla-Pazner S, Alter G. Identification of antibody glycosylation structures that predict monoclonal antibody Fc-effector function. AIDS (London, England) 2014 Nov; 28(17).
Klein F, Nogueira L, Nishimura Y, Phad G, West AP, Halper-Stromberg A, Horwitz JA, Gazumyan A, Liu C, Eisenreich TR, Lehmann C, Fätkenheuer G, Williams C, Shingai M, Martin MA, Bjorkman PJ, Seaman MS, Zolla-Pazner S, Karlsson Hedestam GB, Nussenzweig MC. Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants. The Journal of experimental medicine 2014 Nov; 211(12).
Spurrier B, Sampson J, Gorny MK, Zolla-Pazner S, Kong XP. Functional implications of the binding mode of a human conformation-dependent V2 monoclonal antibody against HIV. Journal of virology 2014 Apr; 88(8).
Yates NL, Liao HX, Fong Y, deCamp A, Vandergrift NA, Williams WT, Alam SM, Ferrari G, Yang ZY, Seaton KE, Berman PW, Alpert MD, Evans DT, O'Connell RJ, Francis D, Sinangil F, Lee C, Nitayaphan S, Rerks-Ngarm S, Kaewkungwal J, Pitisuttithum P, Tartaglia J, Pinter A, Zolla-Pazner S, Gilbert PB, Nabel GJ, Michael NL, Kim JH, Montefiori DC, Haynes BF, Tomaras GD. Vaccine-induced Env V1-V2 IgG3 correlates with lower HIV-1 infection risk and declines soon after vaccination. Science translational medicine 2014 Mar; 6(228).
Zolla-Pazner S. A critical question for HIV vaccine development: which antibodies to induce?. Science (New York, N.Y.) 2014 Jul; 345(6193).
Zolla-Pazner S, deCamp A, Gilbert PB, Williams C, Yates NL, Williams WT, Howington R, Fong Y, Morris DE, Soderberg KA, Irene C, Reichman C, Pinter A, Parks R, Pitisuttithum P, Kaewkungwal J, Rerks-Ngarm S, Nitayaphan S, Andrews C, O'Connell RJ, Yang ZY, Nabel GJ, Kim JH, Michael NL, Montefiori DC, Liao HX, Haynes BF, Tomaras GD. Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection. PloS one 2014; 9(2).
Zolla-Pazner S, Edlefsen PT, Rolland M, Kong XP, deCamp A, Gottardo R, Williams C, Tovanabutra S, Sharpe-Cohen S, Mullins JI, deSouza MS, Karasavvas N, Nitayaphan S, Rerks-Ngarm S, Pitisuttihum P, Kaewkungwal J, O'Connell RJ, Robb ML, Michael NL, Kim JH, Gilbert P. Vaccine-induced Human Antibodies Specific for the Third Variable Region of HIV-1 gp120 Impose Immune Pressure on Infecting Viruses. EBioMedicine 2014 Nov; 1(1).
Wise MC, Hutnick NA, Pollara J, Myles DJ, Williams C, Yan J, LaBranche CC, Khan AS, Sardesai NY, Montefiori D, Barnett SW, Zolla-Pazner S, Ferrari G, Weiner DB. An Enhanced Synthetic Multiclade DNA Prime Induces Improved Cross-Clade-Reactive Functional Antibodies when Combined with an Adjuvanted Protein Boost in Nonhuman Primates. Journal of virology 2015 Sep; 89(18).
Gottardo R, Bailer RT, Korber BT, Gnanakaran S, Phillips J, Shen X, Tomaras GD, Turk E, Imholte G, Eckler L, Wenschuh H, Zerweck J, Greene K, Gao H, Berman PW, Francis D, Sinangil F, Lee C, Nitayaphan S, Rerks-Ngarm S, Kaewkungwal J, Pitisuttithum P, Tartaglia J, Robb ML, Michael NL, Kim JH, Zolla-Pazner S, Haynes BF, Mascola JR, Self S, Gilbert P, Montefiori DC. Plasma IgG to linear epitopes in the V2 and V3 regions of HIV-1 gp120 correlate with a reduced risk of infection in the RV144 vaccine efficacy trial. PloS one 2013; 8(9).
Shen G, Upadhyay C, Zhang J, Pan R, Zolla-Pazner S, Kong XP, Hioe CE. Rationally Targeted Mutations at the V1V2 Domain of the HIV-1 Envelope to Augment Virus Neutralization by Anti-V1V2 Monoclonal Antibodies. PloS one 2015; 10(10).
McFarren A, Lopez L, Williams DW, Veenstra M, Bryan RA, Goldsmith A, Morgenstern A, Bruchertseifer F, Zolla-Pazner S, Gorny MK, Eugenin EA, Berman JW, Dadachova E. A fully human antibody to gp41 selectively eliminates HIV-infected cells that transmigrated across a model human blood brain barrier. AIDS (London, England) 2016 Feb; 30(4).
Balasubramanian P, Kumar R, Williams C, Itri V, Wang S, Lu S, Hessell AJ, Haigwood NL, Sinangil F, Higgins KW, Liu L, Li L, Nyambi P, Gorny MK, Totrov M, Nadas A, Kong XP, Zolla-Pazner S, Hioe CE. Differential induction of anti-V3 crown antibodies with cradle- and ladle-binding modes in response to HIV-1 envelope vaccination. Vaccine 2017 Mar; 35(10).
Mayr LM, Decoville T, Schmidt S, Laumond G, Klingler J, Ducloy C, Bahram S, Zolla-Pazner S, Moog C. Non-neutralizing Antibodies Targeting the V1V2 Domain of HIV Exhibit Strong Antibody-Dependent Cell-mediated Cytotoxic Activity. Scientific reports 2017 Oct; 7(1).
Horwitz JA, Bar-On Y, Lu CL, Fera D, Lockhart AA, Lorenzi JC, Nogueira L, Golijanin J, Scheid JF, Seaman MS, Gazumyan A, Zolla-Pazner S, Nussenzweig MC. Non-neutralizing Antibodies Alter the Course of HIV-1 Infection In Vivo. Cell 2017 Aug; 170(4).
Powell RL, Totrov M, Itri V, Liu X, Fox A, Zolla-Pazner S. Plasticity and Epitope Exposure of the HIV-1 Envelope Trimer. Journal of virology 2017 Sep; 91(17).
Musich T, Li L, Liu L, Zolla-Pazner S, Robert-Guroff M, Gorny MK. Monoclonal Antibodies Specific for the V2, V3, CD4-Binding Site, and gp41 of HIV-1 Mediate Phagocytosis in a Dose-Dependent Manner. Journal of virology 2017 Apr; 91(8).
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Dr.Zolla-Pazner did not report having any of the following types of financial relationships with industry during 2017 and/or 2018: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
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