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Kevin J. Tracey

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Kevin J. Tracey
BornDecember 10, 1957
Fort Wayne, Indiana
NationalityAmerican
EducationBoston College, Boston University, Cornell University Medical Center
OccupationScientist
EmployerFeinstein Institute for Medical Research
Known forMedical Research
Website[1]

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 and President of the Elmezzi Graduate School of Molecular Medicine[1] in Manhasset, New York. His work pioneered the understanding of how the nervous system controls the immune system response to infection and sterile injury.

Education

Kevin J. 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[2] under Prof. Russel Patterson. During this time he was also a guest investigator at Rockefeller University.

Academic appointments

In 1992, Tracey moved to the North Shore-LIJ Health System,[3] 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 and President of the Elmezzi Graduate School of Molecular Medicine[1] in Manhasset, New York. In 2008 ]North Shore LIJ partnered with Hofstra University to establish a new School of Medicine at Hofstra University.[4]

Principal scientific contributions

Tracey studies inflammation, the physiological and immunological response to infection and injury, and the mechanisms by which neurons control its development.[5] In the early 1980s, he and colleagues were first to describe the direct inflammatory activity of tumor necrosis factor-alpha (TNF).[6] This was followed by the first report that monoclonal antibodies against TNF can be effectively used as a therapeutic agent.[7] A subsequently expanding field of research confirmed that TNF is a mediator of septic shock, but not sepsis. This prompted Tracey to search for another mediator of sepsis, culminating in 1999 by identification of HMGB1, a protein previously known as a DNA-binding transcription factor, as a mediator and drug target in sepsis.[8] .[9]

Reasoning that evolution favored physiological mechanisms that maintain homeostasis, Tracey proposed a mechanism for neural control of TNF and HMGB1 to maintain immunological homeostasis. Termed the "Inflammatory reflex",[10] 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.[11] 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.[12] 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.[13] 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.[14].[15] In November of 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.[2]

Awards and honors

Book

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.[17][18]

Multimedia

References

  1. ^ a b "Elmezzi Graduate School".
  2. ^ "Cornell Neurological Surgery Alumni".
  3. ^ "North Shore-LIJ Health System".
  4. ^ "Hofstra North Shore LIJ School of Medicine at Hofstra University".
  5. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1038/nri2566, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1038/nri2566 instead.
  6. ^ Tracey K.J. et al. "Shock and tissue injury induced by recombinant human cachectin". Science. 1986 Oct 24;234(4775):470-4. PMID 3764421
  7. ^ Tracey K.J., Fong Y, Hesse DG, Manogue KR, Lee AT, Kuo GC, Lowry SF, Cerami A. "Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia". Nature. 1987 Dec 17-23;330(6149):662-4. PMID 3317066
  8. ^ Wang H, et al. "HMG-1 as a late mediator of endotoxin lethality in mice". ‘’Science’’. 1999 Jul 9;285(5425):248-51. PMID 10398600
  9. ^ Andersson U, Tracey KJ. "Reflex principles of immunological homeostasis”. ‘’Annu Rev Immunol’’. 2012;30:313-35. PMID 22224768
  10. ^ Tracey K.J. "The inflammatory reflex". Nature. 2002 Dec 19-26;420(6917):853-9. Review. PMID 12490958
  11. ^ Wang H, et al. "Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation". Nature. 2003 Jan 23;421(6921):384-8. Epub 2002 Dec 22. PMID 12508119
  12. ^ Mauricio Rosas-Ballina, Peder S. Olofsson at al. "Acetylcholine-Synthesizing T Cells Relay Neural Signals in a Vagus Nerve Circuit." Science. 2011 Oct 7;334(6052):98-101. PMID 21921156
  13. ^ Tracey K.J. "Physiology and immunology of the cholinergic antiinflammatory pathway". J Clin Invest. 2007 Feb;117(2):289-96. Review. PMID 17273548; PMC 1783813
  14. ^ Tracey K.J. "Reflex control of immunity". Nat Rev Immunol. 2009 Jun;9(6):418-28.Review. PMID 19461672
  15. ^ Andersson U, Tracey K.J. " Reflex principles of immunological homeostasis ". ‘’Annu Rev Immunol’’. 2012;30:313-35. PMID 22224768
  16. ^ "ISI Highly Cited Researchers".
  17. ^ "For Janice - Legacy of a Short Life".
  18. ^ Tracey, K. J. (2005). Fatal Sequence: The Killer Within. New York: Dana Press. ISBN 978-1932594065.

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