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Marzena E. Pazgier, PhD

Academic Title:

Associate Professor

Primary Appointment:

Biochemistry and Molecular Biology

Additional Title:

Head of the Laboratory of Biomolecular Recognition of Institute of Human Virology

Location:

Institute of Human Virology, 725 W. Lombard Street, Room S318

Phone (Primary):

(410) 706-4780

Fax:

(410) 706-7583

Education and Training

1996      B. Eng. Technical Chemistry, Technical University of Lodz, Poland

1996      M. S. Biochemistry and Biotechnology, Technical University of Lodz, Poland

2001      Ph.D. Technical Chemistry of Sciences, Technical University of Lodz, Poland

 

Postgraduate Education and Training

2002-2007           Postdoctoral Fellow, National Cancer Institute, NIH, Frederick, MD, Macromolecular Crystallography Laboratory

 

Biosketch

 

Dr. Pazgier received her M.D. in biochemistry and biotechnology and Ph.D. in technical chemistry from Technical University of Lodz, Poland, and completed her postdoctoral training in protein engineering and structural biology of macromolecules at the National Cancer Institute at Frederick, MD, in the Macromolecular Crystallography Laboratory. In 2007 Dr. Pazgier joined University of Maryland School of Medicine at the Institute of Human Virology and in the Department of Biochemistry and Molecular Biology where in 2009 she established her independent research program in structural biology of infectious disease.

Dr.  Pazgier research focuses on understanding, at the structural level, of mechanisms involved in innate and adaptive responses to infectious disease with the long term goal to generate knowledge required to develop new vaccines or antibody/protein therapeutics. Dr. Pazgier research is highly interdisciplinary, involving structural biology, primarily by X-Ray crystallography, contemporary biophysical and protein engineering techniques, and structure-function analysis. Throughout the course of her scientific career Dr. Pazgier have published over fifty manuscripts, filed two US patent applications, and authored 70 novel structures of proteins or protein complexes that have been deposited in the international Protein Data Bank (PDB). Her research program has been continuously supported by independent grant funds: initially by The Bill and Melinda Gates Foundation, but more recently by NIH R01 and P01 grants. Dr. Pazgier current research focuses on:

  1. Structural Basis of Antibody-Mediated Protection Against HIV-1. These studies are designed to provide the molecular basis of mechanisms governing broad and potent Fc-mediated effector function of antibodies against HIV-1. These studies focus on how epitopes in the HIV-1 envelope glycoprotein (Env) elicit protective responses that are mediated primarily by antibody-dependent cellular cytotoxicity (ADCC). ADCC is a mechanism whereby antigen-antibody complexes on an HIV-1 infected cell arms effector cells (typically NK cells or macrophages) enabling them to lyse the infected cell.

  2. Structural Targeting of Epitopes Involved Protective HIV-1 Response. The structural information gained from studies of Fc-mediated effector mechanisms are used to develop new vaccines and epitope specific reagents capable of inducing ADCC response in animal or human host.

  3. New Strategies for a Functional Cure Through Antibody-Dependent Cell-Mediated Cytotoxicity. The apparent successes of cancer cure strategies that are based on therapeutic antibodies (tAbs) targeting immune checkpoints have caused a reevaluation of the potential for similar strategies for an HIV-1 cure. However, most of the currently explored antibody-based therapies and eradication strategies are based on neutralizing antibodies, especially those that are broadly neutralizing. By contrast, strategies for a functional cure with use of non-neutralizing antibodies (nnAbs) that eliminate HIV-infected cells through Fc receptor (FcR) effector function, including antibody ADCC, remain a significant yet largely unexploited avenue of research. This project is designed to develop new conjugates of ADCC-mediating nnAbs that will be capable of sensitizing HIV-1-infected cells from HIV-1-infected individuals to ADCC-mediated killing.

  4. Molecular Basis for Interaction of Rhesus Macaques (RM) Fcγ Receptors and IgG Subclasses. It is well established that Fcγ receptors (FcγR) are key contributors to antibody activity in vivo across numerous disease settings, including HIV-1. The ultimate goal of this project is to characterize RM FcγR, the RM IgG subclasses and their interactions at the atomic level to provide a better understanding of how antibody biology can be mapped across the human and macaque species barrier to advance promising vaccine concepts and to improve the protective responses that have been observed.
  5. Structure-Function Relationships of Human Defensins. This program investigates structure-function relationship of human α-defensins and other antimicrobial peptides involved in innate responses, such as cathelicidins. The long-term objective of this program is to dissect the structural determinants of interactions of defensins with viral and bacterial membranes and understand a role of oligomerization in their multifunction

Research/Clinical Keywords

structural biology by X-Ray crystallography, HIV-1, defensins, antimicrobial agents, Fc-mediated effector function, antibody dependent cellular cytotoxicity (ADCC), rhesus macaques (RM) Fcγ receptors and IgG subclasses

Highlighted Publications

  1. Gohain N, Tolbert WD, Acharya P, Yu L, Liu T, Zhao P, Orlandi C, Visciano ML, Kamin-Lewis R, Sajadi MM, Martin L, Robinson JE, Kwong PD, DeVico AL, Ray K, Lewis GK, Pazgier M (2015) Co-crystal Structures of Antibody N60-i3 and Antibody JR4 in Complex with gp120 Define More Cluster A Epitopes Involved in Effective Antibody-Dependent Effector Function against HIV-1, J Virol: 1;89(17):8840-54
  2. Lewis GK, Finzi A, DeVico AL, Pazgier M (2015) Conformational Masking and Receptor-Dependent Unmasking of Highly Conserved Env Epitopes Recognized by Non-Neutralizing Antibodies That Mediate Potent ADCC against HIV-1, Viruses: 18;7(9):5115-32.
  3. Tolbert WD, Gohain N, Veillette M, Chapleau J-P, Orlandi Ch, Visciano ML, Ebadi T, DeVico T, Fouts TR, Finzi A, Lewis G, Pazgier M (2016) Paring down HIV-1 Env: Design and Structure of an Independent Inner Domain of gp120 that Stably Expresses the A32 Epitope Sub-region of ADCC Epitope Cluster A, Structure: 24(5):697-709
  4. Richard J, Pacheco B, Gohain N, Veillette M, Ding S, Alsahafi N, Tolbert WD, Prévost J, Chapleau J-P, Coutu M, Jia M, Brassard N, Park J, Courter JR, Melillo B, Martin L, Tremblay C, Hahn BHi, Kaufmanna DE, Wu X, Smith III AS, Sodroski J, Pazgier M, Finzi A (2016) Co-receptor Binding Site Antibodies Enable CD4-Mimetics to Expose Conserved Anti-cluster A ADCC Epitopes on HIV-1 Envelope Glycoproteins,  EBioMedicine:S2352-3964(16)30412-1
  5. Gohain N, Tolbert WD, Orlandi Ch, Richard J , Ding S, Chen X, Bonsor DA, Sundberg EJ, Lu W, Ray K, Finzi A, Lewis GK, Pazgier M. (2016) Molecular basis for epitope recognition by non-neutralizing anti-gp41 antibody F240, Scientific Reports: Nov 9;6:36685. doi: 10.1038/srep36685
  6. Lewis G, Pazgier M, DeVico A (2017) Survivor's Remorse: Antibody-Mediated Protection Against HIV-1; Immunological reviews, Immunol Rev. 2017 Jan;275(1):271-284. doi: 10.1111/imr.12510
  7. Tolbert WD, Gohain N, Alsahafi N, Van V, Orlandi Ch, Ding S, Martin L, Finzi A, Lewis GK, Ray K,  Pazgier M (2017) Targeting the Late Stage of HIV-1 Entry for Antibody-dependent Cellular Cytotoxicity: Structural Basis for Env Epitopes in the C11 Region, Structure, in press

Additional Publication Citations