Kevin J. Tracey
|Kevin J. Tracey|
December 10, 1957 |
Fort Wayne, Indiana
|Institutions||Feinstein Institute for Medical Research|
|Alma mater||Boston University|
Kevin J. Tracey, a neurosurgeon and inventor, was born in Fort Wayne, Indiana on 10 December 1957. He is president of the Feinstein Institute for Medical Research and is professor at and president of the Elmezzi Graduate School of Molecular Medicine in Manhasset, New York.
Tracey received his B.S. in chemistry summa cum laude from Boston College in 1979 and his M.D. from Boston University in 1983. From 1983 to 1992 he trained in neurosurgery at the New York Hospital/Cornell University with Russel Patterson. During this time he was also a guest investigator at Rockefeller University.
In 1992, Tracey moved to the North Shore-LIJ Health System, in Manhasset, New York, where he practiced neurosurgery and established the Laboratory of Biomedical Science. In 2005 he was appointed president and CEO of the Feinstein Institute for Medical Research, and professor at and president of the Elmezzi Graduate School of Molecular Medicine (Manhasset, New York). In 2008, North Shore-LIJ partnered with Hofstra University to establish a new school of medicine at Hofstra University.
Principal scientific contributions
In the early 1980s, with Stephen Lowry (Cornell University Medical Center) and Anthony Cerami (Rockefeller University), he described the direct inflammatory activity of tumor necrosis factor-alpha (TNF). This was followed by a report that specific anti-TNF monoclonal antibodies can be effectively used as a therapeutic agent.
A subsequently expanding field of research confirmed that TNF is a mediator of septic shock (similar to the effects of directly administering TNF to mammals), but not sepsis. This prompted Tracey to search for another mediator of sepsis, culminating in 1999 with the identification of HMGB1, a protein previously known as a DNA-binding transcription factor, as a mediator and drug target in sepsis.
Reasoning that evolution must have favored physiological mechanisms to maintain homeostasis, Tracey proposed a mechanism for neural control of TNF and HMGB1 to maintain immunological homeostasis. Termed the "inflammatory reflex", action potentials carried in the vagus nerve inhibit cytokine release and innate immunity. The neurophysiological mechanism is dependent upon action potentials transmitted in the vagus nerve which activate release of acetylcholine, a neurotransmitter that interacts with alpha-7 nicotinic receptors expressed on the cell surface of macrophages that produce TNF and other cytokines. The interaction of acetylcholine with alpha-7 nicotinic receptors prevents cytokine release by downregulating nuclear activation of NFkB. Stimulating the vagus nerve inhibits potentially damaging cytokine responses, and protects against organ damage caused by unregulated or excessive cytokine release. In 2011 Tracey and his colleagues Mauricio Rosas-Ballina and Peder Olofsson discovered a memory T cell subset that secretes acetylcholine in the spleen when activated by signals arising in the vagus nerve. These T cells are regulated by incoming neurotransmission arising in the brain stem, and respond by producing the terminal neurotransmitter required to complete the inflammatory reflex.
The neural circuit they discovered can be exploited to therapeutic advantage, because application of electrodes to stimulate the vagus nerve (vagus nerve stimulation) protects against damaging inflammation in experimental arthritis, colitis, ischemia, myocardial infarction, congestive heart failure, and other conditions. The importance of the inflammatory reflex in controlling inflammation establishes the concept that the immune system does not function autonomously, but rather its output is coordinated by physiological units of reflex action. In November 2012, Tracey co-authored the report of the first successful clinical trial demonstrating that vagus nerve stimulation can be effective in methotrexate-resistant rheumatoid arthritis patients, findings that were presented at the annual meeting of the American College of Rheumatology.
Awards and honors
- Honorary doctorate from the Karolinska Institute, 2009
- Highly Cited Researcher in Immunology.
Book and editorial activities
- Tracey's book Fatal Sequence: The Killer Within, recounts the course of a young patient with sepsis, a case that influenced Tracey's research into the molecular basis of septic shock, and severe sepsis.
- editor-in-chief, Molecular Medicine
- Advisory editor, Journal of Experimental Medicine
- "Elmezzi Graduate School".
- "Cornell Neurological Surgery Alumni".
- "North Shore-LIJ Health System".
- "Hofstra North Shore LIJ School of Medicine at Hofstra University".
- Tracey, Kevin J. (2009). "Reflex control of immunity". Nature Reviews Immunology 9 (6): 418–28. doi:10.1038/nri2566. PMID 19461672.
- Tracey, KJ; Beutler, B; Lowry, SF; Merryweather, J; Wolpe, S; Milsark, IW; Hariri, RJ; Fahey 3rd, TJ; Zentella, A (1986). "Shock and tissue injury induced by recombinant human cachectin". Science 234 (4775): 470–4. doi:10.1126/science.3764421. PMID 3764421.
- Tracey, KJ; Fong, Y; Hesse, DG; Manogue, KR; Lee, AT; Kuo, GC; Lowry, SF; Cerami, A (1987). "Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia". Nature 330 (6149): 662–4. doi:10.1038/330662a0. PMID 3317066.
- Wang, H; Bloom, O; Zhang, M; Vishnubhakat, JM; Ombrellino, M; Che, J; Frazier, A; Yang, H; Ivanova, S (1999). "HMG-1 as a late mediator of endotoxin lethality in mice". Science 285 (5425): 248–51. doi:10.1126/science.285.5425.248. PMID 10398600.
- Andersson, U; Tracey, KJ (2012). "Reflex principles of immunological homeostasis". Annual review of immunology 30: 313–35. doi:10.1146/annurev-immunol-020711-075015. PMID 22224768.
- Tracey, KJ (2002). "The inflammatory reflex". Nature 420 (6917): 853–9. doi:10.1038/nature01321. PMID 12490958.
- Wang, H; Yu, M; Ochani, M; Amella, CA; Tanovic, M; Susarla, S; Li, JH; Wang, H; Yang, H (2003). "Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation". Nature 421 (6921): 384–8. doi:10.1038/nature01339. PMID 12508119.
- Rosas-Ballina, M; Olofsson, PS; Ochani, M; Valdés-Ferrer, SI; Levine, YA; Reardon, C; Tusche, MW; Pavlov, VA; Andersson, U (2011). "Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit". Science 334 (6052): 98–101. doi:10.1126/science.1209985. PMID 21921156.
- Tracey, KJ (2007). "Physiology and immunology of the cholinergic antiinflammatory pathway". The Journal of clinical investigation 117 (2): 289–96. doi:10.1172/JCI30555. PMC 1783813. PMID 17273548.
- Tracey, KJ (2009). "Reflex control of immunity". Nature reviews. Immunology 9 (6): 418–28. doi:10.1038/nri2566. PMID 19461672.
- "SetPoint Medical Presents Positive Clinical Results for First Human Study of Implantable Neuromodulation Device for Rheumatoid Arthritis". Nov 12, 2012.
- Maria Sjögren. "Honorary doctors at Karolinska Institutet 2009 - Prizes and Awards - Karolinska Institutet". Ki.se. Retrieved 2013-02-07.
- "ISI Highly Cited Researchers".
- "For Janice - Legacy of a Short Life".
- Tracey, K. J. (2005). Fatal Sequence: The Killer Within. New York: Dana Press. ISBN 978-1932594065.