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.

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.)

Yu L., Wan F, Dutta S, Welsh S, Liu Z, Freundt F, Baehrecke, EH, Lenardo M. Autophagic programmed cell death by selective catalase degradation. Proc. Natl. Acad. Sci. USA 103: 4952-4957, 2006.

Oliveira JB, Bidere N, Niemela JE, Zheng L, Sakai K, Nix CP, Danner RL, Barb J, Munson PJ, Puck JM, Dale J, Straus SE, Fleisher TA, Lenardo MJ. NRAS mutation causes a human autoimmune lymphoproliferative syndrome. Proc. Natl. Acad. Sci. USA 104: 8953-8958, 2007.

Wan F, Anderson DE, Barnitz RA, Snow A, Bidere N, Zheng L, Hedge V, Lam LT, Staudt LM, Levens D, Deutsch WA, Lenardo MJ. Ribosomal protein S3: a KH domain subunit in NF-kB complexes that mediates selective gene regulation. Cell 131: 927-939, 2007.

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. 8:1353-1362, 2007.

Pandiyan P, Lenardo MJ. The control of CD4⁺CD25⁺Foxp3⁺ regulatory T cell survival. Biology Direct 3: 6, 2008.

back to top