Study Provides Insights Into Diagnosis, Treatment of Rare Immune Disease: NIH Scientists Report Findings From 20 Years of ALPS Research
Chief, Molecular Development of the Immune System Section, LI
Our laboratory investigates the molecular regulation of T lymphocytes, particularly as it relates to immunological tolerance, apoptosis, and autoimmune diseases such as multiple sclerosis, type 1 diabetes mellitus, and similar diseases. We use both molecular biology and cellular immunology techniques to pursue these investigations, with a focus on programs of cell death and survival, including apoptosis, autophagy, and necrosis mechanisms. Our approach has been to use contemporary genomic approaches to discover the molecular basis of new genetic diseases of the immune system that affect activation, tolerance, and homeostasis and to develop novel means of diagnosis and immunomodulation of these diseases. Also, we are attempting to pioneer a means of antigen-specific induction of apoptosis of pathogenic T cells as a means of treating autoimmune disease. Such studies could lead to a better understanding of molecular regulatory mechanisms that are important for human immunological diseases.
Dr. Lenardo graduated with a B.A. from the Johns Hopkins University and an M.D. from Washington University, St. Louis. He performed clinical work in internal medicine and research at the University of Iowa and received postdoctoral training at the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology. He established an independent research unit in the Laboratory of Immunology in 1989 and became a senior investigator and section chief in 1994. Dr. Lenardo serves on several editorial boards and has given numerous lectures around the world on his work on the molecular regulation of immune homeostasis. His work focuses on lymphocyte apoptosis, autoimmunity, and genomics of the immune system. He was one of the founders of the NIH-Oxford-Cambridge Scholars program for doctoral training and the NIH M.D./Ph.D. partnership program.
Front row from right: Sonia Majri, Chryssa Kanellopoulou, Bernice Lo, Michael Lenardo, Carol Trageser, Maria Hessie, Ping Jiang, Pearl Chen
2nd row from right: Nicole Yung, Helen Matthews, Carrie Lucas, Jian Li, ByungHa Lee, Rebecca Baker, Austin Swafford, Martha Dalton, Wei Lu
3rd row from right: Lixin Zheng, Matt Biancalana, Benjamin Chaigne-Delalande, Daniel Brooks, Kim Shafer-Weaver, Tim Gilpatrick
Chaigne-Delalande B, Li FY, O'Connor GM, Lukacs MJ, Jiang P, Zheng L, Shatzer A, Biancalana M, Pittaluga S, Matthews HF, Jancel TJ, Bleesing JJ, Marsh RA, Kuijpers TW, Nichols KE, Lucas CL, Nagpal S, Mehmet H, Su HC, Cohen JI, Uzel G, Lenardo MJ. Mg2+ regulates cytotoxic functions of NK and CD8 T cells in chronic EBV infection through NKG2D. Science. 2013 Jul 12;341(6142):186-91.
Snow AL, Xiao W, Stinson JR, Lu W, Chaigne-Delalande B, Zheng L, Pittaluga S, Matthews HF, Schmitz R, Jhavar S, Kuchen S, Kardava L, Wang W, Lamborn IT, Jing H, Raffeld M, Moir S, Fleisher TA, Staudt LM, Su HC, Lenardo MJ. Congenital B cell lymphocytosis explained by novel germline CARD11 mutations. J Exp Med. 2012 Nov 19;209(12):2247-61.
Liu Z, Lee J, Krummey S, Lu W, Cai H, Lenardo MJ. The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease. Nat Immunol. 2011 Oct 9;12(11):1063-70.
Li FY, Chaigne-Delalande B, Kanellopoulou C, Davis JC, Matthews HF, Douek DC, Cohen JI, Uzel G, Su HC, Lenardo MJ. Second messenger role for Mg2+ revealed by human T-cell immunodeficiency. Nature. 2011 Jul 27;475(7357):471-6.
Pandiyan P, Conti HR, Zheng L, Peterson AC, Mathern DR, Hernández-Santos N, Edgerton M, Gaffen SL, Lenardo MJ. CD4(+)CD25(+)Foxp3(+) regulatory T cells promote Th17 cells in vitro and enhance host resistance in mouse Candida albicans Th17 cell infection model. Immunity. 2011 Mar 25;34(3):422-34.
Yu L, McPhee CK, Zheng L, Mardones GA, Rong Y, Peng J, Mi N, Zhao Y, Liu Z, Wan F, Hailey DW, Oorschot V, Klumperman J, Baehrecke EH, Lenardo MJ. Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature. 2010 Jun 17;465(7300):942-6.
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Baehrecke EH, Alva A, Lenardo MJ, Li Y, inventors; University of Maryland College Park, National Institutes of Health, assignees. Function of autophagy genes in cell death. United States patent US 7,838,645. 2010 Nov 23.
Lenardo MJ, Chan FKM, Siegel RM, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Identification of a novel domain in the tumor necrosis factor receptor family that mediates pre-ligand receptor assembly and function. United States patent US 7,148,061. 2006 Dec 12.
Nye SH, Lenardo MJ, McFarland HF, Matis LA, Mueller EE, Mueller JP, Pelfrey CM, Squinto SP, Wilkins JA. Modified myelin basic protein molecules. United States patent US 7,041,503. 2006 May 9.
Baltimore D, Sen R, Sharp PA, Singh H, Staudt L, Lebowitz JH, Baldwin AS Jr, Clerc RG, Corcoran LM, Baeuerle PA, Lenardo MJ, Fan CM, Maniatis TP, inventors; President & Fellows of Harvard College, Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research, assignees. Nuclear factors associated with transcriptional regulation. United States patent US 6,410,516. 2002 Jun 25.
Lenardo MJ, Fisher G, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Applicator system. United States patent US 6,312,648. 2001 Nov 6.
Baltimore D, Sen R, Sharp PA, Singh H, Staudt L, Lebowitz JH, Baldwin AS Jr, Clerc RG, Corcoran LM, Baeuerle PA, Lenardo MJ, Fan CM, Maniatis TP, inventors; President & Fellows of Harvard College, Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research, assignees. Nuclear factors associated with transcriptional regulation. United States patent US 6,150,090. 2000 Nov 21.
Visit the U.S. Patent and Trademark Office database for a complete patent listing.
Last Updated January 08, 2014