Kevin J. Tracey

Kevin J. Tracey
Tracey in 2019
Born (1957-12-10) 10 December 1957 (age 66)
Fort Wayne, Indiana
Alma materBoston University
Known forBioelectronic Medicine
Scientific career
FieldsNeurosurgery, immunology
InstitutionsFeinstein Institute for Medical Research
Websitefeinstein.northwell.edu/institutes-researchers/our-researchers/kevin-j-tracey-md

Kevin J. Tracey, a neurosurgeon and inventor, is the president and CEO of the Feinstein Institute for Medical Research, professor of neurosurgery and molecular medicine at the Zucker School of Medicine, and president of the Elmezzi Graduate School of Molecular Medicine[1] in Manhasset, New York. The Public Library of Science Magazine, PLOS Biology, recognized Tracey in 2019 as one of the most cited researchers in the world.[2]

Early life

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Tracey was born in Fort Wayne, Indiana on 10 December 1957. He received his B.S. in chemistry 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[3] with Russel Patterson. During this time he was also a guest investigator at Rockefeller University.[4]

Academic appointments

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In 1992, Tracey moved to Northwell Health,[5] in Manhasset, New York, where he practiced neurosurgery and established the Laboratory of Biomedical Science (now the Center for 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).[1]

Research

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Tracey studies inflammation; he turned to immunological research and inflammation after training as a neurosurgeon, due to his puzzlement over what happened to an 11-month-old girl in his care who died of sepsis.[6] Training as both a neurosurgeon and immunologist merged in discovery of the mechanism by which neurons control the immune system.[7]

In the early 1980s, Tracey and colleagues described the inflammatory activity of TNF and other cytokines as a cytokine capable of causing shock and tissue injury.[8] Because excessive TNF production damages tissues in the body, it was the basis for the discovery and development of disease-modifying antirheumatic drugs for arthritis and inflammatory bowel disease.[6] A subsequently expanding field of research confirmed that TNF is a mediator of septic shock, but not sepsis. This prompted Tracey to search for other mediators of sepsis, culminating in 1999 by discovering high mobility group box 1 (HMGB1), a protein previously known as a DNA-binding transcription factor, is an inflammatory mediator.[9] The discovery of HMGB1 as a damaged associated molecular pattern (DAMP) offered a mechanism for how sterile injury, which causes HMGB1 release, causes inflammation even in the absence of infection.[9]

In the 1990s an accidental result in the Tracey lab led to a discovery of how the brain normally inhibits the production of TNF.[6] They had developed an anti-inflammatory named CNI-1493, or semapimod.[6] Unexpectedly, the CNI-1493 stimulated the vagus nerve to inhibit TNF production in the body.[6] This discovery that the vagus nerve controls the immune system led him to study the effects of stimulating the vagus nerve with electrodes to alleviate inflammation, called "the inflammatory reflex".[10][11][12]

In 2007 he co-founded a company called SetPoint Medical which aimed to develop vagus nerve stimulation devices to treat autoimmune diseases.[10][13][11] The company started clinical trials in 2011, and in 2016 published results for treating patients with rheumatoid arthritis.[10] Vagus nerve stimulation has successfully blocked inflammation in clinical trials of rheumatoid arthritis and inflammatory bowel disease.[14]

The Tracey lab mapped the inflammatory reflex using genetic, immunological, and bioelectronic tools to define the molecular and neuroscience mechanisms.[9] An unexpected finding from this work is the vagus nerve, a parasympathetic nerve, controls the splenic nerve, a sympathetic nerve.[15] Additionally in 2011, Tracey and colleagues discovered a memory T cell subset that secretes acetylcholine in the spleen when activated by signals arising in the vagus nerve, named "T ChAt" cells.[15] These regulatory T cells produce acetylcholine, the chemical signal to macrophages which turns off production of TNF and other inflammatory mediators.[15]

In May 2018, Tracey's team was first to decode specific signals that the nervous system uses to communicate immune status and alert the brain to inflammation. Identifying these neural signals and what they're communicating about the body's health provides insight into diagnostic and therapeutic targets, and device development.[16] In February 2019, Tracey along with a team led by Tak Mak, PhD, and Maureen Cox, PhD, reported that T ChAt regulate the development of immunity during virus infections.[17]

In November 2020, they reported that neurons in the brainstem dorsal motor nucleus (DMN) of the vagus nerve transmit signals to the celiac-superior mesenteric ganglia in the abdomen. This experiment combined optogenetics, anatomical and functional mapping, and measurement of TNF production to show for the first time that parasympathetic vagus neurons control sympathetic splenic neurons, because the parasympathetic and sympathetic nervous systems were believed to be independent.[18]

Awards and honors

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Select publications

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Year Title[29] Publication Author(s) Volume/Issue Citation
2022 Identification of a brainstem locus that inhibits tumor necrosis factor PNAS Kressel AM, Tsaava T, Levine YA, Chang EH, Addorisio ME, Chang Q, Burbach BJ, Carnevale D, Lembo G, Zador AM, Andersson U, Pavlov VA, Chavan SS, Tracey KJ 10.1073/pnas.2008213117
2016 Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis PNAS Koopman FA, Chavan SS, Miljko S, Grazio S, Sokolovic S, Schuurman PR, Mehta AD, Levine YA, Faltys M, Zitnik R, Tracey KJ, Tak PP 10.1073/pnas.1605635113
2011 Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit Science Rosas-Ballina M, Olofsson PS, Ochani M, Valdés-Ferrer SI, Levine YA, Reardon C, Tusche MW, Pavlov VA, Andersson U, Chavan S, Mak TW, Tracey KJ 10.1126/science.1209985
2003 Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation Nature Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, Li JH, Wang H, Yang H, Ulloa L, Al-Abed Y, Czura CJ, Tracey KJ 10.1038/nature01339
2002 The inflammatory reflex Nature Tracey KJ 10.1038/nature01321
2000 Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin Nature Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ 10.1038/35013070
1999 HMG-1 as a late mediator of endotoxin lethality in mice Science Wang H, Bloom O, Zhang M, Vishnubhakat JM, Ombrellino M, Che J, Frazier A, Yang H, Ivanova S, Borovikova L, Manogue KR, Faist E, Abraham E, Andersson J, Andersson U, Molina PE, Abumrad NN, Sama A, Tracey KJ 10.1126/science.285.5425.248

Book and editorial activities

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  • Tracey, K. J. (2005). Fatal Sequence: The Killer Within. New York: Dana Press. ISBN 978-1932594065.
  • Editor-in-chief, Bioelectronic Medicine[30]
  • Advisory Editor, Journal of Experimental Medicine[31]
  • Contributing Editor, Molecular Medicine[32]

References

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  1. ^ a b "Elmezzi Graduate School". 23 May 2024.
  2. ^ Baas, Jeroen; Klavans, Richard; Boyack, Kevin; Ioannidis, John P. A. (2019). "Bibliometrics". Supplementary data tables for "A standardized citation metrics author database annotated for scientific field" (PLoS Biology 2019). Vol. 1. Mendeley. doi:10.17632/btchxktzyw.1. Retrieved 29 September 2019.
  3. ^ "Cornell Neurological Surgery Alumni". 23 January 2013.
  4. ^ "Lecturer Will Discuss Replacing Drugs with Electronic Devices". Kidney News. 8 (10/11): 31. October 2016.
  5. ^ "The Generator by Emily Anthes".
  6. ^ a b c d e Carlson, Emily (September 2010). "Up Close With: Kevin Tracey" (PDF). Findings. Office of Communications and Public Liaison National Institute of General Medical Sciences. pp. 9–16.
  7. ^ Tracey, K. J. (2009). "Reflex control of immunity". Nature Reviews. Immunology. 9 (6): 418–428. doi:10.1038/nri2566. PMC 4535331. PMID 19461672.
  8. ^ Tracey, Kevin (24 October 1986). "Shock and tissue injury induced by recombinant human cachectin". Science. 234 (4775): 470–474. Bibcode:1986Sci...234..470T. doi:10.1126/science.3764421. PMID 3764421. Retrieved 9 June 2021.
  9. ^ a b c Jong, Roh; Dong, Sohn (13 August 2018). "Damage-Associated Molecular Patterns in Inflammatory Diseases". Immune Network. 18 (4): e27. doi:10.4110/in.2018.18.e27. PMC 6117512. PMID 30181915.
  10. ^ a b c Fox, D (3 May 2017). "The shock tactics set to shake up immunology". Nature. 545 (7652): 20–22. Bibcode:2017Natur.545...20F. doi:10.1038/545020a. PMID 28470211. S2CID 4385501. Open access icon
  11. ^ a b Behar, Michael (23 May 2014). "Can the Nervous System Be Hacked?". The New York Times.
  12. ^ Finley, Allysia (22 July 2022). "Electricity Is the New Medical Miracle". The Wall Street Journal. Retrieved 25 August 2022.
  13. ^ Garde, Damien (2013). "SetPoint Medical – 2013 Fierce 15". FierceBiotech.
  14. ^ Waltz, Emily (14 June 2018). "Battling Crohn's Disease with Vagus Nerve Stimulation". Spectrum IEEE. Retrieved 23 February 2021.
  15. ^ a b c Rosas-Ballina, M., et al. "Acetylcholine-Synthesizing T Cells Relay Neural Signals in a Vagus Nerve Circuit". Science, vol. 334, no. 6052, 2011, pp. 98–101., doi:10.1126/science.1209985.
  16. ^ Holme, Frida (May 2018). "Scientists Wants to Decode Body-Brain Nerve Signals to Diagnose Illness". Frontline Genomics.
  17. ^ Zeller, Gregory (February 2019). "Tracey, Global Team Unearth New Bioelectronic Clue". InnovateLI.
  18. ^ "Researchers Discover Possible Pathway of Vagus Nerve's Inflammatory Response". Pain Medicine News. Retrieved 9 June 2021.
  19. ^ "AIMBE College of Fellows Class of 2020". AIMBE. American Institute for Medical and Biological Engineering. Retrieved 14 July 2022.
  20. ^ "The Harvey Society: Lecture Series". The Harvey Society. Retrieved 6 February 2019.
  21. ^ "Grenvik lectureship".
  22. ^ "The Association of American Physicians". The Association of American Physicians. Retrieved 12 February 2019.
  23. ^ "The Nancy L. R. Bucher Seminar Series". Boston University School of Medicine. Retrieved 12 February 2019.
  24. ^ Maria Sjögren. "Honorary doctors at Karolinska Institutet 2009 – Prizes and Awards – Karolinska Institutet". Ki.se. Retrieved 7 February 2013.
  25. ^ "ISI Highly Cited Researchers".
  26. ^ "2007 Stetten Lecture – Physiology and Immunology of the Cholinergic Anti-inflammatory Pathway". NIH National Institute of General Medical Sciences. Retrieved 8 February 2019.
  27. ^ "Member Directory". The American Society of Clinical Investigation. Retrieved 12 February 2019.
  28. ^ Baas, Jeroen; Klavans, Richard; Boyack, Kevin; Ioannidis, John P. A. (2019). "Bibliometrics". Supplementary data tables for "A standardized citation metrics author database annotated for scientific field" (PLoS Biology 2019). Vol. 1. Mendeley. doi:10.17632/btchxktzyw.1. Retrieved 29 September 2019.
  29. ^ "Tracey KJ PubMed Publications". Retrieved 2 November 2021.
  30. ^ "Bioelectronic Medicine". Springer Nature. Retrieved 6 February 2019.
  31. ^ "Journal of Experimental Medicine". Rockefeller University Press. Retrieved 6 February 2019.
  32. ^ "Molecular Medicine Editorial Board". Springer Nature. Retrieved 6 February 2019.
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