Sergio A. Lira
|Sérgio A. Lira, M.D., PhD.|
|Institutions||Mount Sinai Medical Center|
|Alma mater||Universidade Federal de Pernambuco, Brazil
University of California, San Diego
Sérgio A. Lira, M.D., PhD., is a Brazilian-born American immunologist who pioneered the use of genetic approaches to study the function of chemokines. His early studies were the first to show that chemokines played a major role on leukocyte trafficking to the brain, the lung and the thymus.
Lira is currently the Leona M. and Harry B. Helmsley Charitable Trust Professor of Immunology at the Mount Sinai School of Medicine and Director of the Immunology Institute at the Mount Sinai Medical Center, both in New York City. He is the author of more than 120 published articles.
Lira earned an M.D. from Universidade Federal de Pernambuco, in Recife, Brazil, in 1982 and a Ph.D. in physiology and pharmacology from the University of California, San Diego, in 1988. He completed a postdoctoral fellowship at the Department of Cell and Development Biology at the Roche Institute of Molecular Biology, New Jersey, in 1992. From 1992-1996, he was at Bristol-Myers-Squibb Pharmaceutical Research Institute as Head of the Transgenic Unit. He served as Director, Department of Immunology, at the Schering-Plough Research Institute between 1996-2002. He joined the Mount Sinai Medical Center in 2002 as the Irene Diamond Associate Professor of Immunology.
Lira organized the 2003 Keystone Symposium on Chemokines and the 2006 Gordon Research Conference on Chemotactic Cytokines. He was elected to the Henry Kunkel Society in 2006 and to the Association of American Physicians in 2008. He received the Inventor’s Award (in 2000) and the Impact Award (in 1998) from the Schering-Plough Research Institute.
Areas of research
Lira’s lab pioneered the use of genetic approaches to study the function of chemokines during homeostasis and disease conditions. Other contributions include studies on the mechanisms of lymphoid neogenesis and on the biological function of molecules encoded by viruses that mimic chemokines, including the discovery that the chemokine receptor encoded by herpesvirus 8 is an oncogene, a discovery that led to important insights into the mechanisms leading to the development of Kaposi’s sarcoma. Lira’s lab has also made important contributions to the study of IL-23, a cytokine that affects development of inflammatory and autoimmune conditions.
Honors and awards
- Max Planck Gesellschaft (Germany) - Student Fellowship. February 1980 - June 1980.
- International Endocrine Society - Travel Award. International Congress of Endocrinology, Kyoto, Japan. 1988.
- President's Award - Bristol-Myers Squibb Company. 1995
- Impact Award - Schering-Plough Research Institute. 1998
- Inventor’s Award - Schering-Plough Research Institute. 2000
- Irene Diamond Associate Professorship in Immunology Award – July 2002.
- Elected to the Henry Kunkel Society – May 2006
- Elected to the Association of American Physicians – April 2008
- Bongers G, Maussang D, Muniz LR, Noriega VM, Fraile-Ramos A, Barker N, Marchesi F, Thirunarayanan N, Vischer HF, Qin L, Mayer L, Harpaz N, Leurs R, Furtado GC, Clevers H, Tortorella D, Smit MJ, Lira SA. The cytomegalovirus-encoded chemokine receptor US28 promotes intestinal neoplasia in transgenic mice. J Clin Invest 2010;120:3969-3978.
- Furtado GC, Marinkovic T, Martin AP, Garin A, Hoch B, Hubner W, Chen BK, Genden E, Skobe M, Lira SA. Lymphotoxin beta receptor signaling is required for inflammatory lymphangiogenesis in the thyroid. Proc Natl Acad Sci USA 2007;104:5026-5031.
- Marinkovic T, Garin A, Yokota Y, Fu Y-X, Ruddle NH, Furtado GC, Lira SA. Interaction of mature CD3+CD4+ T cells with dendritic cells triggers the development of tertiary lymphoid structures in the thyroid. J Clin Invest 2006;116:2622-2632.
- Grisotto MG, Garin A, Martin AP, Jensen KK, Chan P, Sealfon SC, Lira SA. The human herpesvirus 8 chemokine receptor vGPCR triggers autonomous proliferation of endothelial cells. J Clin Invest 2006;116:1264-1273.
- Jamieson T, Cook DN, Nibbs RJB, Rot A, Nixon C, McLean P, Alcami A, Lira SA, Wiekowski M, Graham GJ. The chemokine receptor D6 limits the inflammatory response in vivo. Nat Immunol 2005;6:403-411.
- Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, Lucian L, To W, Kwan S, Churakova T, Zurawski S, Wiekowski M, Lira SA, Gorman D, Kastelein RA, Sedgwick JD. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 2003;421:744-748.
- Chen S-C, Vassileva G, Kinsley D, Holzmann S, Manfra D, Wiekowski MT, Romani N, Lira SA. Ectopic expression of the murine chemokines CCL21a and CCL21b induces the formation of lymph node-like structures in pancreas, but not skin, of transgenic mice. J Immunol 2002;168:1001-1008.
- Wiekowski MT, Leach MW, Evans EW, Sullivan L, Chen SC, Vassileva G, Bazan JF, Gorman DM, Kastelein RA, Narula S, Lira SA. Ubiquitous transgenic expression of the IL-23 subunit p19 induces multiorgan inflammation, runting, infertility, and premature death. J Immunol 2001;166:7563-7570.
- CXCL13 expression in the gut promotes accumulation of IL-22-producing lymphoid tissue-inducer cells, and formation of isolated lymphoid follicles. Marchesi F, Martin AP, Thirunarayanan N, Devany E, Mayer L, Grisotto MG, Furtado GC, Lira SA. Mucosal Immunol. 2009 Nov;2(6):486-94. Epub 2009 Sep 9. PMID 19741597
- Holst PJ, Rosenkilde MM, Manfra D, Chen SC, Wiekowski MT, Holst B, Cifire F, Lipp M, Schwartz TW, Lira SA. Tumorigenesis induced by the HHV8-encoded chemokine receptor requires ligand modulation of high constitutive activity. J Clin Invest 2001;108:1789-1796.
- Cook DN, Chen SC, Sullivan LM, Manfra DJ, Wiekowski MT, Prosser DM, Vassileva G, Lira SA. Generation and analysis of mice lacking the chemokine fractalkine. Mol Cell Biol 2001;21:3159-3165.
- Chensue SW, Lukacs NW, Yang TY, Shang X, Frait KA, Kunkel SL, Kung T, Wiekowski MT, Hedrick JA, Cook DN, Zingoni A, Narula SK, Zlotnik A, Barrat FJ, O'Garra A, Napolitano M, Lira SA. Aberrant in vivo T helper type 2 cell response and impaired eosinophil recruitment in CC chemokine receptor 8 knockout mice. J Exp Med 2001;193:573-584.
- Yang TY, Chen SC, Leach MW, Manfra D, Homey B, Wiekowski M, Sullivan L, Jenh CH, Narula SK, Chensue SW, Lira SA. Transgenic expression of the chemokine receptor encoded by human herpesvirus 8 induces an angioproliferative disease resembling Kaposi's sarcoma. J Exp Med 2000;191:445-454.
- Cook DN, Prosser DM, Forster R, Zhang J, Kuklin NA, Abbondanzo SJ, Niu XD, Chen SC, Manfra DJ, Wiekowski MT, Sullivan LM, Smith SR, Greenberg HB, Narula SK, Lipp M, Lira SA. CCR6 mediates dendritic cell localization, lymphocyte homeostasis, and immune responses in mucosal tissue. Immunity 2000;12:495-503.
- Vassileva G, Soto H, Zlotnik A, Nakano H, Kakiuchi T, Hedrick JA, Lira SA. The reduced expression of 6Ckine in the plt mouse results from the deletion of one of two 6Ckine genes. J Exp Med 1999;190:1183-1188.
- Tani M, Fuentes ME, Peterson JW, Trapp BD, Durham SK, Loy JK, Bravo R, Ransohoff RM, Lira SA. Neutrophil infiltration, glial reaction, and neurological disease in transgenic mice expressing the chemokine N51/KC in oligodendrocytes. J Clin Invest 1996;98:529-539.
- Weih F, Carrasco D, Durham SK, Barton DS, Rizzo CA, Ryseck RP, Lira SA, Bravo R. Multiorgan inflammation and hematopoietic abnormalities in mice with a targeted disruption of RelB, a member of the NF-kappa B/Rel family. Cell 1995;80:331-340.
- Fuentes ME, Durham SK, Swerdel MR, Lewin AC, Barton DS, Megill JR, Bravo R, Lira SA. Controlled recruitment of monocytes and macrophages to specific organs through transgenic expression of monocyte chemoattractant protein-1. J Immunol 1995;155:5769-5776.
- Smeyne RJ, Klein R, Schnapp A, Long LK, Bryant S, Lewin A, Lira SA, Barbacid M. Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene. Nature 1994;368:246-249.
- Lira SA, Zalamea P, Heinrich JN, Fuentes ME, Carrasco D, Lewin AC, Barton DS, Durham S, Bravo R. Expression of the chemokine N51/KC in the thymus and epidermis of transgenic mice results in marked infiltration of a single class of inflammatory cells. J Exp Med 1994;180:2039-2048.
- Lira SA, Crenshaw EB, Glass CK, Swanson LW, Rosenfeld MG. Identification of rat growth hormone genomic sequences targeting pituitary expression in transgenic mice. Proc Natl Acad Sci USA 1988;85:4755-4759.
- Nelson C, Crenshaw EB, Franco R, Lira SA, Albert VR, Evans RM, Rosenfeld MG. Discrete cis-active genomic sequences dictate the pituitary cell type-specific expression of rat prolactin and growth hormone genes. Nature 1986;322:557-562.
- Reboldi A, Coisne C, Baumjohann D, Benvenuto F, Bottinelli D, Lira S, Uccelli A, Lanzavecchia A, Engelhardt B, Sallusto F (May 2009). "C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE". Nat. Immunol. 10 (5): 514–23. doi:10.1038/ni.1716. PMID 19305396.
- "Wiley::Chemokine Receptors as Drug Targets". Retrieved April 26, 2011.
- "Mount Sinai School of Medicine - Faculty profile". Retrieved April 26, 2011.
- Gerd Folkers; Martine J. Smit; Sergio A. Lira; Leurs, Rob; Raimund Mannhold; Hugo Kubinyi (2010). Chemokine Receptors as Drug Targets (Methods and Principles in Medicinal Chemistry). Weinheim: Wiley-VCH. ISBN 3-527-32118-7.
- Sánchez MP, Silos-Santiago I, Frisén J, He B, Lira SA, Barbacid M (July 1996). "Renal agenesis and the absence of enteric neurons in mice lacking GDNF". Nature 382 (6586): 70–3. doi:10.1038/382070a0. PMID 8657306.
- "Journal of Clinical Investigation". Retrieved April 26, 2011.
- Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, Lucian L, To W, Kwan S, Churakova T, Zurawski S, Wiekowski M, Lira SA, Gorman D, Kastelein RA, Sedgwick JD (February 2003). "Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain". Nature 421 (6924): 744–8. doi:10.1038/nature01355. PMID 12610626.
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