Susan Zolla-Pazner, PhD
Dr. Susan Zolla-Pazner is a professor in the departments of Medicine and Microbiology at the Icahn School of Medicine at Mount Sinai and a guest investigator at the Rockefeller University. Her work has been pivotal in establishing the central role of antibodies in protection from HIV infection and thereby helping to focus the efforts of the HIV vaccine field on humoral immunity as a preventive approach, leading the American Association for the Advancement of Science to refer to her as an “antibody person.” Named one of “Six Prominent Women Scientists Making a Difference in the AIDS Fight” (IAVIReport), she has discussed her vaccine-development work on PBS’s “Charlie Rose” show.
Building on her decades of research into the antigenic and structural nature of the second and third variable region (V2 and V3) of the HIV envelope glycoprotein, gp120, Dr. Zolla-Pazner measured the levels of antibodies (Abs) specific for these regions in the vaccine and placebo recipients of the RV144 clinical vaccine trial in Thailand. These were 2 of more than 100 assays run by scientists around the globe to determine if there was an immune correlate of the reduced rate of HIV infection in the vaccine recipients. Independent statistical analyses of the data indicated that the only independent correlate of reduced infection was the level of V2 Abs in the sera of vaccine recipients. These results indicated that, as Dr. Zolla-Pazner had hypothesized more than 10 years before, Abs to variable regions of gp120 play a crucial role in protection from infection. In addition, Dr. Zolla-Pazner measure Ab levels to several additional sites on gp120 at various times after the end of the immunization protocol of the trial. She showed that Abs reached maximal levels 2 weeks after the last immunization and dropped to background levels 6 months later. These findings corresponded with data showing that maximum protection from infection occurred in the first 6 months after the immunization period, and that there would be little if any protection thereafter. Together, these results strongly suggested that antibodies were a key to protection from HIV infection, a highly controversial point until the findings of the Zolla-Pazner lab.
Dr. Zolla-Pazner and her colleagues have spent the last 10 years developing “designer vaccines,” i. e., V2- and V3-scaffold proteins that focus Ab production on these regions of gp120. Her studies in rabbits and nonhuman primates have demonstrated that structure-based recombinant vaccines induce Abs that react with the envelopes of viruses from diverse HIV subgroups and have biologic activity, including neutralization and phagocytosis.
Research History
In 1981, Dr. Zolla-Pazner was among the first scientists to describe the immunologic abnormalities of patients presenting with Kaposi’s sarcoma associated with a then-mysterious illness. She provided the initial descriptions of immunologic abnormalities in the first patients with AIDS-related Mycobacterium avium-intracellulare infection and identified similar immunologic abnormalities in apparently healthy gay men who later developed AIDS. This work was the first indication of the chilling reality that one-third of gay men in New York City were suffering from a fatal but as-yet-unidentified illness.
In the early days of the AIDS epidemic, the Zolla-Pazner lab described the hyperactivation of B lymphocytes in HIV-infected individuals. This discovery led Dr. Zolla-Pazner to develop methods to generate anti-HIV human monoclonal antibodies (mAbs) from blood 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 with strong neutralizing potency targeting a quaternary neutralizing epitope that includes the V2 loop of the HIV envelope protein.
Graduate and Postdoctoral Studies
Following undergraduate studies at Stanford University, Susan Zolla-Pazner received her Ph.D. in medical microbiology at the University of California Medical Center, San Francisco. Her doctoral studies, a continuation of the pioneering immunochemical work of Drs. Michael Heidelberger and Elvin Kabat, were focused on the immunochemical characteristics of antipneumococcal Abs and the unusual isotype of these Abs in horse sera, which were used as a treatment for pneumonia prior to the advent of antibiotics. Dr Zolla-Pazner spent 2 years as a postdoctoral fellow at the NYU School of Medicine, working with Dr. Edward C. Franklin, where she studied immunoglobulin synthesis in myeloma cells derived from human bone marrow. These studies led to several years of investigation into how plasma cell tumors affect the induction of Ab responses in mice.
Early Work
In 1969, Dr. Zolla-Pazner established her own laboratory at the New York Veterans Affairs Hospital, part of the NYU School of Medicine in Manhattan. As an assistant professor in the Department of Pathology at NYU, she continued her work on mouse plasmacytomas, and, in 1977, she also became the director of the VA Clinical Immunology Laboratory, the only lab in the NYU/VA complex to assess the function of immune responses in human patients.
As noted, Dr. Zolla-Pazner was one of the pioneer scientists to describe the immunologic abnormalities in the disease that came to be knows as the acquired immunodeficiency syndrome, or AIDS. Her research focused on the abnormalities of B lymphocytes in patients with AIDS and with early forms of HIV infection. Eventually, Dr. Zolla-Pazner’s interests settled on studies of the “variable regions” of the gp120 envelope glycoprotein of HIV. Her lab was the first to describe how Abs to the V2 and V3 regions of gp120 could recognize these regions in viruses from all over the globe, despite extreme variability in these regions of amino acid sequences. These studies indicated that the V2 and V3 regions of diverse strains of HIV share common immunologic structures.
Dr Zolla-Pazner’s structural studies of the V3 loop of the HIV envelope illustrated their conserved structure despite their amino acid variability. Additionally, her structural studies of V2 showed that the V1V2 region of the HIV envelope also has a conserved structure. These immunologic and structural studies demonstrated how V2 and V3 from diverse viruses share antigenic similarities, contributing to our understanding of how V3 helps the virus infect cells through cell surface coreceptors—the chemokine receptors CXCR4 and CCR5—and how the V1V2 region forms the apex of the virus’s envelope trimer and assists in protecting vulnerable areas of the envelope from Abs.
Grants and Memberships
Since beginning her independent research in 1969, Dr. Zolla-Pazner has received continuous funding and has 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. She has published over 300 papers in journals including Science, Journal of Infectious Diseases, Journal of Immunology, Journal of Virology, Nature Structural and Molecular Biology, and New England Journal of Medicine. She is an elected fellow of the American Association for the Advancement of Science (AAAS) and the American Society for Microbiology (ASM). Click here for a listing of awards and honors.
Dr. Zolla-Pazner is married to Sherman Pazner, MD. She is the mother of 2 sons, Evan and Toby, and grandmother of Zoe and Ezra. She is a patron of the arts and has been a moving force behind the development of Music at Mount Sinai, a program that provides monthly musical concerts for patients and staff at the Mount Sinai School of Medicine.