Michael J. Lenardo, M.D.
Chief, Molecular Development of the Immune System Section
Description of Research Program
Our laboratory investigates the molecular regulation of T lymphocytes, particularly as it relates to immunological tolerance, apoptosis, and autoimmune diseases such as multiple sclerosis, myasthenia gravis, and similar diseases. We use both molecular biology and cellular immunology techniques to pursue these investigations. Our goal is to understand the pathogenesis of autoimmunity from the vantage point of T-cell regulation as well as develop novel means of immunomodulation of these diseases.
Recently we have also undertaken the investigation of how the human immunodeficiency virus (HIV) causes the death of CD4 T lymphocytes. Such studies could lead to a better understanding of viral pathogenesis as well as the development of new treatments for, or vaccines against, AIDS.
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| NF-kB (stained in green) translocation from the cytosol to the nucleus (red) is impaired following B-cell receptor (αlg) but not CD40L stimulation, in a patient deficient for caspase-8 compared to his healthy mother. Analysis of NF-kB nuclear translocation revealed a new function of caspase-8 in lymphocyte activation in addition to its well known role in apoptosis. This discovery was made by analyzing the molecular mechanism of immunodeficiency in patients with caspase-8 deficiency state (CEDS). |
Research Group Members
Front row, left to right: Pushpa Pandiyan, Maria G. Hessie, Monika Jung, Eric Freundt, Zhihua Liu and Michael Lenardo. Back row, left to right: Helen Su, Diane Bolton, Aleishia Harris, Morgan Mandigo, Carol Trageser, Tony Barnitz, Fengyi Wan, Li Yu, Nicolas Bidere. Not pictured: Lixin Zheng, Parmesh Dutt, Andy Snow, Keiko Sakai, and Guo-Min Deng.
Selected Publications
(View list in PubMed.)
Freundt EC, Yu L, Goldsmith CS, Welsh S, Cheng A, Yount B, Liu W, Frieman MB, Buchholz UJ, Screaton GR, Lippincott-Schwartz J, Zaki SR, Xu XN, Baric RS, Subbarao K, Lenardo MJ. The ORF 3a protein of SARS-CoV promotes membrane rearrangement and cell death. J Virol. 2009 Nov 4. [Epub ahead of print]
Snow AL, Marsh RA, Krummey SM, Roehrs P, Young LR, Zhang K, van Hoff J, Dhar D, Nichols KE, Filipovich AH, Su HC, Bleesing JJ, Lenardo MJ. Restimulation-induced apoptosis of T cells is impaired in patients with X-linked lymphoproliferative disease caused by SAP deficiency. J Clin Invest. 2009 Oct;119(10):2976-89.
Johnson AL, Aravind L, Shulzhenko N, Morgun A, Choi SY, Crockford TL, Lambe T, Domaschenz H, Kucharska EM, Zheng L, Vinuesa CG, Lenardo MJ, Goodnow CC, Cornall RJ, Schwartz RH. Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection. Nat Immunol. 2009 Aug;10(8):831-9.
Bidére N, Ngo VN, Lee J, Collins C, Zheng L, Wan F, Davis RE, Lenz G, Anderson DE, Arnoult D, Vazquez A, Sakai K, Zhang J, Meng Z, Veenstra TD, Staudt LM, Lenardo MJ. Casein kinase 1alpha governs antigen-receptor-induced NF-kappaB activation and human lymphoma cell survival. Nature. 2009 Mar 5;458(7234):92-6.
Pandiyan P, Zheng L, Ishihara S, Reed J, Lenardo MJ. CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nat Immunol. 2007 Dec;8(12):1353-62.
Wan F, Anderson DE, Barnitz RA, Snow A, Bidere N, Zheng L, Hegde V, Lam LT, Staudt LM, Levens D, Deutsch WA, Lenardo MJ. Ribosomal protein S3: a KH domain subunit in NF-kappaB complexes that mediates selective gene regulation. Cell. 2007 Nov 30;131(5):927-39.
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