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.
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
- Kwong B, Rua R, Gao Y, Flickinger J Jr, Wang Y, Kruhlak MJ, Zhu J, Vivier E, McGavern DB, Lazarevic V. T-bet-dependent NKp46+ innate lymphoid cells regulate the onset of TH17-induced neuroinflammation. Nat Immunol. 2017;18(10):1117-1127.
- Wang Y, Godec J, Ben-Aissa K, Cui K, Zhao K, Pucsek AB, Lee YK, Weaver CT, Yagi R, Lazarevic V. The transcription factors T-bet and Runx are required for the ontogeny of pathogenic interferon-γ-producing T helper 17 cells. Immunity. 2014;40(3):355-66.
- Lazarevic V, Glimcher LH, Lord GM. T-bet: a bridge between innate and adaptive immunity. Nat Rev Immunol. 2013;13(11):777-89.
- Lazarevic V, Glimcher LH. T-bet in disease. Nat Immunol. 2011;12(7):597-606.
- Lazarevic V, Chen X, Shim JH, Hwang ES, Jang E, Bolm AN, Oukka M, Kuchroo VK, Glimcher LH. T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the gene encoding RORγt. Nat Immunol. 2011;12(1):96-104.
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This page was last updated on Thursday, October 6, 2022