Vanja Lazarevic, Ph.D.

Vanja  Lazarevic, Ph.D.
Investigator
Immunopathogenesis Unit

Dr. Lazarevic’s laboratory is interested in how transcription factors regulate differentiation and effector function of CD4+ T helper (Th) cells in the context of autoimmune disorders with emphasis on experimental autoimmune encephalomyelitis, a model for multiple sclerosis.

Her research is focused on understanding the molecular basis for functional plasticity of CD4+ Th cells and identifying CD4+ T cell-specific, pathogenicity-associated genes required for initiation and propagation of inflammation. Transcription factor T-bet has been linked to the development of several autoimmune diseases. Dr. Lazarevic’s laboratory is validating the importance of T-bet target genes in driving the pathogenesis of multiple sclerosis with the aim of developing new lines of therapeutic agents.

Areas of Expertise
1) CD4 T helper cells, 2) transcription factors, 3) autoimmunity

Contact Info

Vanja Lazarevic, Ph.D.
Center for Cancer Research
National Cancer Institute
Building 10 - Magnuson CC, Room 5A31/33
Bethesda, MD 20892
Ph: 301-402-3246
lazarevicv@mail.nih.gov

Our laboratory studies the molecular events that lead to the breakdown of immunological tolerance to self-antigens. These processes are clinically manifested in the development of autoimmune diseases, such as multiple sclerosis or rheumatoid arthritis.

The function of the immune system is to defend the host against viral, bacterial, fungal and parasitic challenges. This protection is mediated through the cells of both innate and adaptive immunity. The cells of adaptive immunity (T cells and B cells) possess antigen-specific receptors of extraordinary diversity in order to protect the body from pathogens. A by-product of this system is the generation of T and B cell subsets which possess receptors that recognize host antigens ("self-antigens"). Exquisite mechanisms have evolved to suppress these autoreactive cells and prevent them from activation by self-antigens. When self-tolerance fails due to environmental or genetic factors, susceptible individuals develop autoimmune diseases which affect either specific organs or the entire body (systemic autoimmunity).

The focus of our laboratory is to understand at a fundamental level the gene products (with a special emphasis on transcription factors) responsible for the breakdown of self-tolerance.

To elucidate the nature of immunological dysregulation that leads to the development of autoimmunity, our lab is focused on the pathogenesis of multiple sclerosis. This is a complex disease in which cells of the immune system attack the protective myelin sheath that wraps around neurons in the brain, spinal cord and optic nerves. Relentless and unchecked immune system activation in the central nervous system (CNS) leads to irreversible neuronal damage and, ultimately, paralysis of affected individuals.

Most of our understanding of the pathogenesis of multiple sclerosis comes from investigations using an experimental autoimmune encephalomyelitis (EAE) animal model. In this model, both CD4+ Th1 and Th17 cells contribute to the pathogenesis of the disease. Our overall goal is to understand how transcription factors and their downstream targets affect CD4+ Th cell differentiation and effector function in the context of autoimmune diseases using this EAE animal model.

Postdoctoral Fellowships
The Immunopathogenesis Unit periodically has openings for outstanding postdoctoral fellows. Please send your C.V. and statement of interest to lazarevicv@mail.nih.gov

Scientific Focus Areas:
Immunology, Neuroscience
View Dr. Lazarevic's PubMed Summary.

Selected Recent Publications

  1. Kwong B, Rua R, Gao Y, Flickinger J Jr, Wang Y, Kruhlak MJ, Zhu J, Vivier E, McGavern DB, Lazarevic V.
    Nature Immunology. 18(10): 1117-1127, 2017. [ Journal Article ]
  2. Wang Y, Godec J, Ben-Aissa K, Cui K, Zhao K, Pucsek AB, Lee YK, Weaver CT, Yagi R, and Lazarevic V.
    Immunity. 40: 355-366, 2014. [ Journal Article ]
  3. Lazarevic V, Glimcher LH, and Lord GM.
    Nature Reviews Immunology. 13(11): 777-789, 2013. [ Journal Article ]
  4. Lazarevic V, and Glimcher LH.
    Nature Immunology. 12(7): 597-606, 2011. [ Journal Article ]
  5. Lazarevic V, Chen X, Shim JH, Hwang ES, Jang E, Bolm AN, Oukka M, Kuchroo VK, and Glimcher LH.
    Nature Immunology. 12(1): 306-313, 2011. [ Journal Article ]

B.Sc., Microbiology, University of Nottingham, Nottingham, UK

Ph.D., Molecular Virology and Microbiology, University of Pittsburgh, Pittsburgh, PA

Postdoctoral Fellow, Immunology Senior Research Associate, Laboratory of Dr. Laurie H. Glimcher, Harvard School of Public Health, Boston, MA

Name Position
Yuanyuan Gao Ph.D. Postdoctoral Fellow (Visiting)
Tiffany Loo Postbaccalaureate Fellow (CRTA)
Michael Lu M.S. Biologist
Yan Wang Ph.D. Biologist