Sergio A. Lira
Encyclopedia
Sergio A. Lira, M.D., PhD., is an immunologist
who pioneered the use of genetic approaches to study the function of chemokine
s. 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 Co-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.
, 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.
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.
Immunology
Immunology is a broad branch of biomedical science that covers the study of all aspects of the immune system in all organisms. It deals with the physiological functioning of the immune system in states of both health and diseases; malfunctions of the immune system in immunological disorders ; the...
who pioneered the use of genetic approaches to study the function of chemokine
Chemokine
Chemokines are a family of small cytokines, or proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines...
s. His early studies were the first to show that chemokines played a major role on leukocyte trafficking to the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
, the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
and the thymus
Thymus
The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....
.
Lira is currently the Leona M. and Harry B. Helmsley Charitable Trust Professor of Immunology at the Mount Sinai School of Medicine
Mount Sinai School of Medicine
Mount Sinai School of Medicine is an American medical school in the borough of Manhattan in New York City, currently ranked among the top 20 medical schools in the United States. It was chartered by Mount Sinai Hospital in 1963....
and Co-Director of the Immunology Institute at the Mount Sinai Medical Center
Mount Sinai Hospital, New York
Mount Sinai Hospital, founded in 1852, is one of the oldest and largest teaching hospitals in the United States. In 2011-2012, Mount Sinai Hospital was ranked as one of America's best hospitals by U.S...
, both in New York City
New York City
New York is the most populous city in the United States and the center of the New York Metropolitan Area, one of the most populous metropolitan areas in the world. New York exerts a significant impact upon global commerce, finance, media, art, fashion, research, technology, education, and...
. He is the author of more than 120 published articles.
Biography
Lira earned an M.D. from Universidade Federal de PernambucoFederal University of Pernambuco
The Federal University of Pernambuco is a public university located in Recife, Brazil, and established in 1946. UFPE has 70 undergraduate courses and 175 postgraduate courses. As of 2007, UFPE had near 35,000 students and about 2,000 professors. The university has three campuses: Recife, Vitória...
, in Recife
Recife
Recife is the fifth-largest metropolitan area in Brazil with 4,136,506 inhabitants, the largest metropolitan area of the North/Northeast Regions, the 5th-largest metropolitan influence area in Brazil, and the capital and largest city of the state of Pernambuco. The population of the city proper...
, Brazil
Brazil
Brazil , officially the Federative Republic of Brazil , is the largest country in South America. It is the world's fifth largest country, both by geographical area and by population with over 192 million people...
, in 1982 and a Ph.D. in physiology
Physiology
Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...
and pharmacology
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...
from the University of California, San Diego
University of California, San Diego
The University of California, San Diego, commonly known as UCSD or UC San Diego, is a public research university located in the La Jolla neighborhood of San Diego, California, United States...
, in 1988. He completed a postdoctoral fellowship at the Department of Cell and Development Biology at the Roche Institute of Molecular Biology
Roche Institute of Molecular Biology
The Roche Institute of Molecular Biology was created on July 14, 1967 when Jim Burns, then the vice president of research at Hoffman-La Roche, persuaded biochemist Sidney Udenfriend to leave the National Institutes of Health and help him create a basic science institute at the Hoffman-La Roche,...
, 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
Schering-Plough
Schering-Plough Corporation was a United States-based pharmaceutical company. It was founded in 1851 by Ernst Christian Friedrich Schering as Schering AG in Germany. In 1971, the Schering Corporation merged with Plough to form Schering-Plough. On November 4, 2009 Merck & Co...
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
Association of American Physicians
The Association of American Physicians is a medical society founded in 1885 by the Canadian physician Sir William Osler and six other distinguished physicians of his era, for "the advancement of scientific and practical medicine." Election to the AAP is an honor extended to individuals with...
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 lymphoidLymphoid
Lymphoid is a term used to describe lymph or the lymphatic system.In the context of lymphoid leukemia, it refers specifically to lymphocytes Lymphoid leukemias and lymphomas are now considered to be tumors of the same type of cell lineage. They are called "leukemia" when in the blood or marrow and...
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
Kaposi's sarcoma-associated herpesvirus
Kaposi's sarcoma-associated herpesvirus is one of seven currently known human cancer viruses, or oncoviruses. It is also the eighth human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses is HHV-8. Like other herpesviruses, its informal name is used...
is an oncogene
Oncogene
An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are often mutated or expressed at high levels.An oncogene is a gene found in the chromosomes of tumor cells whose activation is associated with the initial and continuing conversion of normal cells into cancer...
, 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
Interleukin 23
Interleukin-23 subunit alpha is a protein that in humans is encoded by the IL23A gene. IL-23 is produced by dendritic cells and macrophages...
, 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 Asociate Professorship in Immunology Award – July 2002.
- Elected to the Henry Kunkel Society – May 2006
- Elected to the Association of American PhysiciansAssociation of American PhysiciansThe Association of American Physicians is a medical society founded in 1885 by the Canadian physician Sir William Osler and six other distinguished physicians of his era, for "the advancement of scientific and practical medicine." Election to the AAP is an honor extended to individuals with...
– April 2008
Publications
Partial list:- Bongers G, Maussang D, Muniz LR, Noriega VM, Fraile-Ramos A, Barker N, Marchesi F, Thirunarayanan N, Vischer HF, Qin L, Mayer LLloyd MayerLloyd Mayer, is an American gastroenterologist and immunologist. He is Professor and Co-Director of the Immunology institute at the Mount Sinai Medical Center...
, 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 SCStuart C. SealfonStuart C. Sealfon, M.D., is an American neurologist who studies the mechanisms of both the therapeutic and adverse effects of drugs. He was an early adopter of the use of massively parallel qPCR and fluorescent in situ hybridization to characterize cell response state and his research...
, 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 LLloyd MayerLloyd Mayer, is an American gastroenterologist and immunologist. He is Professor and Co-Director of the Immunology institute at the Mount Sinai Medical Center...
, 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.
External links
- The Mount Sinai Medical Center homepage
- The Mount Sinai School of Medicine homepage
- The Immunology Institute at the Mount Sinai Medical Center