Infectious Disease Lab – Dr. Pazgier

ABOUT

Dr. Marzena Pazgier's laboratory investigates the molecular mechanisms that regulate antibody-mediated immunity against infectious diseases through an interdisciplinary research program spanning structural biology, immunology, and translational medicine. Researchers seek to understand how the structural organization and conformational dynamics of viral antigens influence immune recognition, Fc-mediated antibody effector functions, and host protection. They focus on pathogens of major clinical and public health importance, including HIV-1, SARS-CoV-2, herpes simplex virus (HSV), and multidrug-resistant bacteria. In alignment with the university’s mission to support military readiness and protection against infectious threats, the group translates structural and mechanistic insights into the rational design of next-generation vaccines, antibody-based therapeutics to combat emerging and persistent infectious diseases.

CURRENT RESEARCH

  • Structural Basis of HIV-1 Env Susceptibility to Fc-effector Functions
    We study how structural variation in the HIV-1 envelope glycoprotein (Env) regulates susceptibility to immune-mediated clearance. Using cryo-EM and complementary biophysical approaches, we have shown that subtype-dependent conformational dynamics govern transitions between “closed” and “open” Env states, thereby controlling the exposure of vulnerable epitopes. By elucidating the molecular determinants that govern Env conformational states, we seek to identify therapeutic targets that increase the immune vulnerability of HIV-1 and to inform the rational engineering of immunogens, such as our recently developed ADCC-focused immunogen, ID2.

  • Fc-Effector Function-Based Strategies Toward an HIV-1 Cure
    We are developing strategies that rely on Fc-effector functions to reduce viral reservoirs and advance functional cure strategies for HIV-1. Using structural biology, we design small-molecule therapeutics that sensitize infected cells to ADCC mediated by monoclonal antibodies or naturally occurring antibodies in PLWH. In parallel, we also engineer antibodies targeting conserved CD4-induced epitopes into therapeutic formats that enhance immune clearance. 

  • Comparative Fc-Mediated Immunity Across Species
    To improve the translation of preclinical findings to human health applications, we are investigating Fc-mediated antibody functions across species. These studies strengthen the predictive value of the non-human primate models widely used in vaccine and therapeutic development and support our mission to accelerate the development of effective vaccines and therapeutics against infectious threats.

  • Structural Immunology of SARS-CoV-2 and Emerging Viral Threats
    In response to emerging infectious disease threats, we apply structural biology to understand antibody-mediated immunity against SARS-CoV-2 and other emerging pathogens. We define mechanisms of neutralization and Fc-effector function, including ADCC, and use these insights to guide the development of vaccines, monoclonal antibodies, and engineered receptor-based biologics (like ACE2 IgG). This work supports preparedness against current and future biologic threats relevant to military operations.

  • Human Defensins and Antimicrobial Therapeutics
    We use human defensins as a platform for developing novel antimicrobial strategies against multidrug-resistant organisms associated with combat trauma and chronic wound infections. We define how structural features, such as hydrophobic interactions, oligomerization, and membrane targeting, govern antimicrobial activity and immune engagement. These insights enable us to engineer defensin-based therapeutics with enhanced stability and potency, addressing infection control challenges in austere and operational environments.

ACTIVE FUNDING

  • NIH R01 AI174908, "New Strategy to Eliminate HIV-1-Infected Cells by Unlocking the Env Trimer"
  • NIH R01 AI150322, "Exploring HIV-1 Env Open Conformations for Therapeutic Intervention"
  • NIH P01 AI162242, "Impact of Antibody Effector Function Diversity on Antiviral Activity In Situ"
  • NIH R01 AI186809, "Targeting the HIV-1 Reservoir at ART Initiation with CD4-Mimetic Interventions"
  • ViiV Healthcare, "Structural Basis for Temsavir Interaction with CRF01_AE HIV-1"
  • NIH R01 AI174979, "Examining the Protective Capacity of a Vaccine-Elicited Potent Neutralizing Antibody Lineage in Rhesus Macaques"
  • NIH R01 AI176646, "Understanding and Optimizing Antibody-Based Interventions Against Neonatal HSV Infection"
  • CIHR PUU-177958, "SARS-CoV-2 Spike Conformation: Impact on Fc-Mediated Effector Functions"
  • NIH R01 AI197950 (Pending), "Characterizing Rare Env-Expressing Cells from People with HIV Virally Suppressed on ART: Informing Env-Targeted Cure Strategies"
     

TEAM 

Dr. Pazgier has extensive experience mentoring trainees across multiple levels and disciplines, including undergraduate and graduate students, Ph.D. candidates, postdoctoral fellows, and military trainees, including cadets. She actively engages trainees in hypothesis-driven research in structural biology and immunology, providing guidance in experimental design, data analysis, and scientific communication.

William D. Tolbert, Ph.D.

William D. Tolbert, Ph.D.

Scientist II
william.tolbert.ctr@usuhs.edu
Dr. Tolbert received his A.B. in chemistry from Cornell University and his M.S. and Ph.D. degrees in biology from the University of Virginia. He completed postdoctoral training in the Department of Biochemistry at the University of Kentucky, Lexington, the Department of Chemistry and Chemical Biology at Cornell University, and the Institute of Human Virology and Department of Biochemistry and Molecular Biology at the University of Maryland, Baltimore. Dr. Tolbert also worked as a Research Scientist at the Van Andel Research Institute. His expertise is in the structural biology of macromolecules and molecular biology.
 

Marek K Korzeniowski, Ph.D.

Marek K Korzeniowski, Ph.D.

Scientist I
marek.korzeniowski.ctr@usuhs.edu
Dr. Korzeniowski graduated from the Polish Academy of Science, Nencki Institute of Experimental Biology with a degree in cell biology. He studied the immunoreceptor gamma signaling cascade. His postdoctoral training was done in the Tamas Balla lab at NICHD, where he analyzed the molecular mechanism of Store Operated Calcium Entry. He also worked in the Baird-Holowka lab at Cornell University to continue studies on SOCE in immune cells. Following that, he joined the Burnett lab at USU to research protein degradation in SMA. He has expertise in molecular cell biology, protein biochemistry, electron and confocal microscopy, and protein engineering techniques.

Ling Niu, MD, Ph.D.

Ling Niu, MD, Ph.D.

Postdoctoral Fellow
ling.niu.ctr@usuhs.edu
Dr. Niu received his medical degree from Wuhan University and his doctorate in biochemistry and molecular biology from the Chinese Academy of Science. Previously, he worked at Nanyang Technological University for about four years developing peptide and protein conjugation techniques. He also spent four years at Iowa State University on HIV and SARS-CoV-2 vaccine development. Dr. Niu’s research interest is in structure-based drug and vaccine design.

Suneetha Gottumukkala, MS

Suneetha Gottumukkala, MS

Research Assistant I
suneetha.gottumukkala.ctr@usuhs.edu
Mrs. Gottumukkala studied microbiology, biochemistry, and chemistry at CH. S. D. St. Theresa's College in India. Prior to joining Dr. Pazgier’s lab, she was a research trainee at a government hospital and a special research volunteer at NIH. Her expertise is in bacterial and mammalian cell cultures, molecular biology, and protein purification.

Monika Chandravanshi, Ph.D.

Monika Chandravanshi

Associate Scientist
Monika.chandravanshi.ctr@usuhs.edu
Dr. Chandravanshi completed her doctoral studies at the Indian Institute of Technology Guwahati, India, where she earned her Ph.D. in bioscience and bioengineering in 2021. Her research focuses on the structure and function of ABC transporters. Following the completion of her Ph.D., Dr. Chandravanshi joined the National Cancer Institute (NCI). There, she contributed to the development of structure-based inhibitors for the treatment of hematological cancers. In 2024, she joined the Pazgier Lab, where her current research is centered on elucidating the structure of the HIV-1 envelope glycoprotein and its interactions with antibodies and inhibitors. Her work aims to support the rational design of therapeutics, including bispecific antibodies, for HIV-1.
 

Vandana Mishra, Ph.D.

Vandana Mishra, Ph.D.

Postdoctoral Fellow
vandana.mishra.ctr.fn@usuhs.edu
Dr. Mishra earned her Ph.D. in structural biology from the Indian Institute of Technology (IIT) in Bombay, India. During her doctoral and research associate work there, she extensively used X-ray crystallography and biophysical approaches for structure-based design of antimalarial inhibitors. Vandana moved to the National Institutes of Health (NIH) in Bethesda for her postdoctoral training. There, she characterized the mechanisms of DNA-repair proteases using biophysical methods, and later at the NIDDK, she studied the cell mitochondrial fusion processes using cryo-EM and cryo-ET. Vandana joined the Pazgier Lab in 2026. Her current research aims to understand the Fc-mediated effector functions to help create better treatments for HIV.