Kevin J. Tracey

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 Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, 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]

Kevin J. Tracey
Tracey in 2019
Born (1957-12-10) 10 December 1957
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

Early life

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.

Academic appointments

In 1992, Tracey moved to Northwell Health,[4] 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

Tracey studies inflammation; he turned to immunological research and inflammation after training as a neurosurgeon, due to his puzzlement over what happened to a young woman in his care who died of sepsis.[5] Training as both a neurosurgeon and immunologist merged in discovery of the mechanism by which neurons control the immune system.[6]

In the early 1980s, Tracey and colleagues described the inflammatory activity of TNF and other cytokines. 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.[5] 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. [7] The discovery of HMGB1 as a damaged associated molecular pattern offered a mechanism for how sterile injury, which causes HMGB1 release, causes inflammation even in the absence of infection.[7]

In the 1990's an accidental result in the Tracey lab led to a discovery of how the brain normally inhibits the production of TNF.[5] They had developed an anti-inflammatory named CNI-1493, or semapimod.[5] Unexpectedly, the CNI-1493 stimulated the vagus nerve which once activated turned down TNF production in the body.[5] Reasoning the discovery of the vagus nerve controlling the immune system, he next studied the effects of stimulating the vagus nerve with electricity to alleviate inflammation, called "the inflammatory reflex".[8][9]In 2007 he co-founded a company called SetPoint Medical which aimed to develop vagus nerve stimulation devices to treat autoimmune diseases.[8][10][9] The company started clinical trials in 2011, and results published in 2016.[8] 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.[11]

In May 2018, Tracey was part of a team that 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.[12]

In February 2019, Tracey along with a team led by Tak Mak, PhD and Maureen Cox, PhD, reported that T cell–derived acetylcholine (ACh) play an important role in regulating immunity.[13]

Awards and honors

Book and editorial activities
  • Tracey, K. J. (2005). Fatal Sequence: The Killer Within. New York: Dana Press. ISBN 978-1932594065.
  • Editor-in-chief, Bioelectronic Medicine[23]
  • Advisory Editor, Journal of Experimental Medicine[24]
  • Contributing Editor, Molecular Medicine[25]

List of Publications

 Due to the number of articles Tracey published, this section is a work in progress. [26]

Year Title Publication Author(s) Volume/Issue Citation
2019 Choline acetyltransferase-expressing T cells are required to control chronic viral infection Science Cox MA, Duncan GS, Lin GHY, Steinberg BE, Yu LX, Brenner D, Buckler LN, Elia AJ, Wakeham AC, Nieman B, Dominguez-Brauer C, Elford AR, Gill KT, Kubli SP, Haight J, Berger T, Ohashi PS, Tracey KJ, Olofsson PS, Mak TW. 10.1126/science.aau9072
2019 HMGB1-C1q complexes regulate macrophage function by switching between leukotriene and specialized proresolving mediator biosynthesis PNAS Liu T, Xiang A, Peng T, Doran AC, Tracey KJ, Barnes BJ, Tabas I, Son M, Diamond B. 10.1073/pnas.1907490116
2018 Molecular and Functional Neuroscience in Immunity Annual Review of Immunology Pavlov VA, Chavan SS, Tracey KJ. 10.1146/annurev-immunol-042617-053158
2018 Identification of cytokine-specific sensory neural signals by decoding murine vagus nerve activity PNAS Zanos TP, Silverman HA, Levy T, Tsaava T, Battinelli E, Lorraine PW, Ashe JM, Chavan SS, Tracey KJ, Bouton CE. 10.1073/pnas.1719083115
2018 The Endotoxin Delivery Protein HMGB1 Mediates Caspase-11-Dependent Lethality in Sepsis Immunity Deng M, Tang Y, Li W, Wang X, Zhang R, Zhang X, Zhao X, Liu J, Tang C, Liu Z, Huang Y, Peng H, Xiao L, Tang D, Scott MJ, Wang Q, Liu J, Xiao X, Watkins S, Li J, Yang H, Wang H, Chen F, Tracey KJ, Billiar TR, Lu B. 10.1016/j.immuni.2018.08.016
2017 Mechanisms and Therapeutic Relevance of Neuro-immune Communication Immunity Chavan SS, Pavlov VA, Tracey KJ. 10.1016/j.immuni.2017.06.008
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
2015 MD-2 is required for disulfide HMGB1-dependent TLR4 signaling Journal of Experimental Medicine Yang H, Wang H, Ju Z, Ragab AA, Lundbäck P, Long W, Valdes-Ferrer SI, He M, Pribis JP, Li J, Lu B, Gero D, Szabo C, Antoine DJ, Harris HE, Golenbock DT, Meng J, Roth J, Chavan SS, Andersson U, Billiar TR, Tracey KJ, Al-Abed Y. 10.1084/jem.20141318
2015 Sepsis: a roadmap for future research The Lancet Infectious Diseases Cohen J, Vincent JL, Adhikari NK, Machado FR, Angus DC, Calandra T, Jaton K, Giulieri S, Delaloye J, Opal S, Tracey K, van der Poll T, Pelfrene E. 10.1016/S1473-3099(15)70112-X
2014 JAK/STAT1 signaling promotes HMGB1 hyperacetylation and nuclear translocation PNAS Lu B, Antoine DJ, Kwan K, Lundbäck P, Wähämaa H, Schierbeck H, Robinson M, Van Zoelen MA, Yang H, Li J, Erlandsson-Harris H, Chavan SS, Wang H, Andersson U, Tracey KJ. 10.1073/pnas.1316925111
2014 Sepsis: current dogma and new perspectives Immunity Deutschman CS, Tracey KJ. 10.1016/j.immuni.2014.04.001
2014 Hypertension: an immune disorder? Immunity Tracey KJ. 10.1016/j.immuni.2014.11.007
2013 Lymphocyte-derived ACh regulates local innate but not adaptive immunity PNAS Reardon C, Duncan GS, Brüstle A, Brenner D, Tusche MW, Olofsson PS, Rosas-Ballina M, Tracey KJ, Mak TW. 10.1073/pnas.1221655110
2013 Sepsis definitions: time for change Lancet Vincent JL, Opal SM, Marshall JC, Tracey KJ. 10.1016/S0140-6736(12)61815-7
2012 Reflex principles of immunological homeostasis Annual Review of Immunology Andersson U, Tracey KJ. 10.1146/annurev-immunol-020711-075015
2012 Neural reflexes in inflammation and immunity Journal of Experimental Medicine Andersson U, Tracey KJ. 10.1084/jem.20120571
2012 Novel role of PKR in inflammasome activation and HMGB1 release Nature Lu B, Nakamura T, Inouye K, Li J, Tang Y, Lundbäck P, Valdes-Ferrer SI, Olofsson PS, Kalb T, Roth J, Zou Y, Erlandsson-Harris H, Yang H, Ting JP, Wang H, Andersson U, Antoine DJ, Chavan SS, Hotamisligil GS, Tracey KJ. 10.1038/nature11290
2011 HMGB1 is a therapeutic target for sterile inflammation and infection Annual Review of Immunology Andersson U, Tracey KJ. 10.1146/annurev-immunol-030409-101323
2011 Mapping the immunological homunculus PNAS Diamond B, Tracey KJ. 10.1073/pnas.1100329108
2011 Thyroxine is a potential endogenous antagonist of macrophage migration inhibitory factor (MIF) activity PNAS Al-Abed Y, Metz CN, Cheng KF, Aljabari B, VanPatten S, Blau S, Lee H, Ochani M, Pavlov VA, Coleman T, Meurice N, Tracey KJ, Miller EJ. 10.1073/pnas.1017624108
2011 Cell biology. Ancient neurons regulate immunity Science Tracey KJ. 10.1126/science.1206353
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
2010 A critical cysteine is required for HMGB1 binding to Toll-like receptor 4 and activation of macrophage cytokine release PNAS Yang H, Hreggvidsdottir HS, Palmblad K, Wang H, Ochani M, Li J, Lu B, Chavan S, Rosas-Ballina M, Al-Abed Y, Akira S, Bierhaus A, Erlandsson-Harris H, Andersson U, Tracey KJ. 10.1073/pnas.1003893107
2009 Reflex control of immunity Nature Reviews Immunology Tracey KJ. 10.1038/nri2566
2008 Splenic nerve is required for cholinergic anti inflammatory pathway control of TNF in endotoxemia PNAS Rosas-Ballina M, Ochani M, Parrish WR, Ochani K, Harris YT, Huston JM, Chavan S, Tracey KJ. 10.1073/pnas.0803237105
2007 Physiology and immunology of the cholinergic anti inflammatory pathway Journal of Clinical Investigation Tracey KJ. 10.1172/JCI30555
2006 Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia PNAS Pavlov VA, Ochani M, Gallowitsch-Puerta M, Ochani K, Huston JM, Czura CJ, Al-Abed Y, Tracey KJ. 10.1073/pnas.0600506103
2005 Cholinergic stimulation blocks endothelial cell activation and leukocyte recruitment during inflammation Journal of Experimental Medicine Saeed RW, Varma S, Peng-Nemeroff T, Sherry B, Balakhaneh D, Huston J, Tracey KJ, Al-Abed Y, Metz CN. 10.1084/jem.20040463
2004 Reversing established sepsis with antagonists of endogenous high-mobility group box 1 PNAS Yang H, Ochani M, Li J, Qiang X, Tanovic M, Harris HE, Susarla SM, Ulloa L, Wang H, DiRaimo R, Czura CJ, Wang H, Roth J, Warren HS, Fink MP, Fenton MJ, Andersson U, Tracey KJ. 10.1073/pnas.2434651100
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
2002 Neuroprotection in cerebral ischemia by neutralization of 3-aminopropanal PNAS Ivanova S, Batliwalla F, Mocco J, Kiss S, Huang J, Mack W, Coon A, Eaton JW, Al-Abed Y, Gregersen PK, Shohami E, Connolly ES Jr, Tracey KJ. 10.1073/pnas.082609299
2002 Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation PNAS Ulloa L, Ochani M, Yang H, Tanovic M, Halperin D, Yang R, Czura CJ, Fink MP, Tracey KJ. 10.1073/pnas.192222999
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
1998 The tetravalent guanylhydrazone CNI-1493 blocks the toxic effects of interleukin-2 without diminishing antitumor efficacy PNAS Kemeny MM, Botchkina GI, Ochani M, Bianchi M, Urmacher C, Tracey KJ. 10.1073/pnas.95.8.4561
1998 Fetuin (alpha2-HS-glycoprotein) opsonizes cationic macrophagedeactivating molecules PNAS Wang H, Zhang M, Bianchi M, Sherry B, Sama A, Tracey KJ. 10.1073/pnas.95.24.14429
1997 Spermine inhibits proinflammatory cytokine synthesis in human mononuclear cells: a counterregulatory mechanism that restrains the immune response Journal of Experimental Medicine Zhang M, Caragine T, Wang H, Cohen PS, Botchkina G, Soda K, Bianchi M, Ulrich P, Cerami A, Sherry B, Tracey KJ. 10.1084/jem.185.10.1759
1997 Fetuin protects the fetus from TNF Lancet Wang H, Zhang M, Soda K, Sama A, Tracey KJ. 10.1016/S0140-6736(05)62030-2
1996 Suppression of proinflammatory cytokines in monocytes by a tetravalent guanylhydrazone Journal of Experimental Medicine Bianchi M, Bloom O, Raabe T, Cohen PS, Chesney J, Sherry B, Schmidtmayerova H, Calandra T, Zhang X, Bukrinsky M, Ulrich P, Cerami A, Tracey KJ. 10.1084/jem.183.3.927
1996 CNI-1493 inhibits monocyte/macrophage tumor necrosis factor by suppression of translation efficiency PNAS Cohen PS, Nakshatri H, Dennis J, Caragine T, Bianchi M, Cerami A, Tracey KJ. 10.1073/pnas.93.9.3967
1993 MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia Nature Bernhagen J, Calandra T, Mitchell RA, Martin SB, Tracey KJ, Voelter W, Manogue KR, Cerami A, Bucala R. 10.1038/365756a0
1988 Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation Journal of Experimental Medicine Tracey KJ, Wei H, Manogue KR, Fong Y, Hesse DG, Nguyen HT, Kuo GC, Beutler B, Cotran RS, Cerami A, et al. 10.1084/jem.167.3.1211
1987 Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia Nature Tracey KJ, Fong Y, Hesse DG, Manogue KR, Lee AT, Kuo GC, Lowry SF, Cerami A. 10.1038/330662a0
1986 Cachectin/tumor necrosis factor mediates changes of skeletal muscle plasma membrane potential Journal of Experimental Medicine Tracey KJ, Lowry SF, Beutler B, Cerami A, Albert JD, Shires GT. 10.1084/jem.164.4.1368
1986 Shock and tissue injury induced by recombinant human cachectin Science Tracey KJ, Beutler B, Lowry SF, Merryweather J, Wolpe S, Milsark IW, Hariri RJ, Fahey TJ 3rd, Zentella A, Albert JD, et al. 10.1126/science.3764421

References
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  2. "Supplementary data tables for "A standardized citation metrics author database annotated for scientific field" (PLoS Biology 2019)". Mendeley. Retrieved 29 September 2019.
  3. "Cornell Neurological Surgery Alumni". 23 January 2013.
  4. "The Generator by Emily Anthes".
  5. 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.
  6. Tracey, K. J. (2009). "Reflex control of immunity". Nature Reviews. Immunology. 9 (6): 418–428. doi:10.1038/nri2566. PMC 4535331. PMID 19461672.
  7. Jong, Roh; Dong, Sohn (13 August 2018). "Damage-Associated Molecular Patterns in Inflammatory Diseases". Immune Network. doi:10.4110/in.2018.18.e27. PMC 6117512. PMID 30181915.
  8. 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.
  9. Behar, Michael (23 May 2014). "Can the Nervous System Be Hacked?". The New York Times.
  10. Garde, Damien (2013). "SetPoint Medical – 2013 Fierce 15". FierceBiotech.
  11. 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.
  12. Holme, Frida (May 2018). "Scientists Wants to Decode Body-Brain Nerve Signals to Diagnose Illness". Frontline Genomics.
  13. Zeller, Gregory (February 2019). "Tracey, Global Team Unearth New Bioelectronic Clue". InnovateLI.
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