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Kevin J. Tracey

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Kevin J. Tracey (b. 10 December 1957, Fort Wayne, IN, USA) is Director of The Feinstein Institute for Medical Research and Professor and President of the Elmezzi Graduate School of Molecular Medicine in Manhasset, NY. Although trained as a neurosurgeon, he is an immunologist who studies the physiological and molecular mechanisms involved with inflammation and disease and, in particular, for investigating how the nervous system controls the responses of the immune system to a threat.

Principle scientific contributions

Tracey's studies unravel the molecular basis of inflammation, and discover how immunity is controlled by neural reflexes. His 1986 paper in Science [1] described the direct inflammatory activities of TNF, and his 1987 paper in Nature [2] showed that monoclonal antibodies against TNF can be used therapeutically to prevent inflammation and tissue injury. He continued to search for other molecules that could be therapeutically targeted, and in 1999 his team reported in Science [3] the discovery that HMGB1, a protein previously known only as a transcription factor, is an inflammatory mediator and drug target. HMGB1 is a mediator of potentially lethal systemic inflammation. Nat Rev Immunol [4]. This has possible applications in the treatment of rheumatoid arthritis, Crohn's disease, and multiple sclerosis.[5][6] Tracey also studies how immunity is controlled by neural reflexes. This mechanism connecting brain and body is analogous to the control of blood pressure and heart rate. The vagus nerve regulates innate immunity through a molecular mechanism of signal transduction dependent upon the nicotinic alpha 7 acetylcholine receptor, which is expressed on innate and adpative immune cells to control the response to invasion Nature [7] Nature [8] Nature [9]. The immune system can no longer be regarded as autonomous, but rather its output is coordinated by physiological units of reflex action Nat Rev Immunol [10].


Education and Appointments

Tracey received his B.S. (Chemistry) from Boston College in 1979 and his M.D. from Boston University in 1983. From 1983 to 1992 he trained as a neurosurgeon at the New York Hospital/Cornell University Medical Center and was a guest investigator at Rockefeller University, working in the laboratory of Anthony Cerami. In 1992, Tracey moved to North Shore University Hospital, where he practiced neurosurgery while building the research program. In 2001, he was appointed the founding program director for the General Clinical Research Center[11], which received designation from the National Center for Research Resources (NCRR) of the National Institutes of Health (NIH). In 2005, Tracey was appointed Director of The Feinstein Institute for Medical Research.

Aand honors

In 2009, Tracey received an honorary doctoral degree from the Karolinska Institute in Stockholm. He was elected as a member of the Association of American Physicians in 2009. In 2007, he delivered the DeWitt Stetten lectureship from The National Institutes of Health, and the Annual Clinical Science Lectureship in 2002 from the Karolinska Institute. Tracey has given invited lectureships at Harvard, Yale, The Rockefeller University, The Scripps Institute and the University of Texas Southwestern. He co-chaired the first international scientific congress addressing "The Inflammatory Reflex", a Nobel Symposium [12] in 2004 of the Karolinska Institute and co-chaired the "First HMGB1 Cytokine World Congress" in 2003 in Saltsjobaden, Sweden. Tracey is Editor in Chief of Molecular Medicine, and Advisory Editor of the Journal of Experimental Medicine. The Institute for Scientific Information named him a "Highly Cited Researcher in Immunology" [13]. Tracey is an elected member of the American Society of Clinical Investigation (2001).

His book Fatal Sequence: The Killer Within, was published by the Dana Press in 2005. In it, he recounts the hospital course of a young patient with sepsis who changed his life, and the series of remarkable events that shaped his research.

References

  1. ^ Science 24;234(4775):470-4.
  2. ^ Nature 23;330(6149):662-4.
  3. ^ Science 285(5425):248-51.
  4. ^ Nat Rev Immunol 5;(4):331-42.
  5. ^ Jacoby, Mary (December 29, 2001). "Foundations' founder yet to donate $67-million". St. Petersburg Times. {{cite web}}: Italic or bold markup not allowed in: |publisher= (help)
  6. ^ Jacoby, Mary (July 8, 2001). "Complex web benefits foundation founder". St. Petersburg Times. {{cite web}}: Italic or bold markup not allowed in: |publisher= (help)
  7. ^ Nature 421;(6921):384-8.
  8. ^ Nature 420;(6917):853-9.
  9. ^ Nature 405;(6785):458-62.
  10. ^ Nat Rev Immunol 9(6):418-28.
  11. ^ [1]
  12. ^ vp30
  13. ^ http://isihighlycited.com




Key Publications

  • 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 (1999). Identification of HMG-1 as a late mediator of endotoxin lethality in mice. Science 285(5425):248-251.
  • Andersson U, Wang H, Palmblad K, Aveberger AC, Bloom O, Erlander-Harris H, Janson A, Kokkola R, Zhang M, Yang H, Tracey KJ (2000). High mobility group 1 protein (HMG1) stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med 192(4):565-570.
  • 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 (2004). Reversing established sepsis with antagonists of endogenous high-mobility group box 1. Proc Natl Acad Sci USA 101(1):296-301.
  • Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ (2000). Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405:458-62.
  • Bernik TR, Friedman ST, Ochani M, DiRaimo R, Ulloa L, Yang H, Sudan S, Czura CJ, Ivanova S, Tracey KJ (2002). Pharmacological stimulation of the Cholinergic Antiinflammatory Pathway. J Exp Med 195:781-788.
  • Tracey KJ (2002) The Inflammatory Reflex. Nature 420:853-859.
  • Wang H, Yu M, Amella CA, Ochani M, Tanovic M, Susarla S, Li JH, Wang H, Ulloa L, Al-Abed Y, Czura CJ, Tracey KJ (2003) Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation. Nature 421:384-388.
  • Wang H, Liao H, Ochani M, Justiniani M, Lin X, Yang L, Al-Abed Y, Wang H, Metz C, Miller EJ, Tracey KJ, Ulloa L (2004). Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med. 10:1216-21.
  • Huston JM, Ochani M, Rosas-Ballina M, Liao H, Ochani K, Pavlov VA, Gallowitsch-Puerta M, Ashok M, Czura CJ, Foxwell B, Tracey KJ, Ulloa L (2006). Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis. J Exp Med. 203:1623-8.
  • Pavlov VA, Ochani M, Gallowitsch-Puerta M, Ochani K, Huston JM, Czura CJ, Al-Abed Y, Tracey KJ (2006). Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia. Proc Natl Acad Sci U S A. 103:5219-23.
  • 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 (1999). Identification of HMG-1 as a late mediator of endotoxin lethality in mice. Science 285(5425):248-251.
  • Andersson U, Wang H, Palmblad K, Aveberger AC, Bloom O, Erlander-Harris H, Janson A, Kokkola R, Zhang M, Yang H, Tracey KJ (2000). High mobility group 1 protein (HMG1) stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med 192(4):565-570.
  • 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 (2004). Reversing established sepsis with antagonists of endogenous high-mobility group box 1. Proc Natl Acad Sci USA 101(1):296-301.
  • Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ (2000). Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405:458-62.
  • Bernik TR, Friedman ST, Ochani M, DiRaimo R, Ulloa L, Yang H, Sudan S, Czura CJ, Ivanova S, Tracey KJ (2002). Pharmacological stimulation of the Cholinergic Antiinflammatory Pathway. J Exp Med 195:781-788.
  • Tracey KJ (2002) The Inflammatory Reflex. Nature 420:853-859.
  • Wang H, Yu M, Amella CA, Ochani M, Tanovic M, Susarla S, Li JH, Wang H, Ulloa L, Al-Abed Y, Czura CJ, Tracey KJ (2003) Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation. Nature 421:384-388.
  • Wang H, Liao H, Ochani M, Justiniani M, Lin X, Yang L, Al-Abed Y, Wang H, Metz C, Miller EJ, Tracey KJ, Ulloa L (2004). Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med. 10:1216-21.
  • Huston JM, Ochani M, Rosas-Ballina M, Liao H, Ochani K, Pavlov VA, Gallowitsch-Puerta M, Ashok M, Czura CJ, Foxwell B, Tracey KJ, Ulloa L (2006). Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis. J Exp Med. 203:1623-8.
  • Pavlov VA, Ochani M, Gallowitsch-Puerta M, Ochani K, Huston JM, Czura CJ, Al-Abed Y, Tracey KJ (2006). Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia. Proc Natl Acad Sci U S A. 103:5219-23.
  • Tracey KJ (2007). Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest. 117:289-96.* Tracey KJ (2007). Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest. 117:289-96.* Tracey KJ, Beutler B, Lowry SF, Merryweather J, Wolpe S, Milsark IW, Hariri RJ, Fahey III TJ, Zentella A, Albert JD, Shires GT, Cerami A (1986). Shock and tissue injury induced by recombinant human cachectin. Science 234:470 474.
  • 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 bacteremia in baboons. Nature 330:662-664.
  • 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 (1999). Identification of HMG-1 as a late mediator of endotoxin lethality in mice. Science 285(5425):248-251.
  • Andersson U, Wang H, Palmblad K, Aveberger AC, Bloom O, Erlander-Harris H, Janson A, Kokkola R, Zhang M, Yang H, Tracey KJ (2000). High mobility group 1 protein (HMG1) stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med 192(4):565-570.
  • 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 (2004). Reversing established sepsis with antagonists of endogenous high-mobility group box 1. Proc Natl Acad Sci USA 101(1):296-301.
  • Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ (2000). Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405:458-62.
  • Bernik TR, Friedman ST, Ochani M, DiRaimo R, Ulloa L, Yang H, Sudan S, Czura CJ, Ivanova S, Tracey KJ (2002). Pharmacological stimulation of the Cholinergic Antiinflammatory Pathway. J Exp Med 195:781-788.
  • Tracey KJ (2002) The Inflammatory Reflex. Nature 420:853-859.
  • Wang H, Yu M, Amella CA, Ochani M, Tanovic M, Susarla S, Li JH, Wang H, Ulloa L, Al-Abed Y, Czura CJ, Tracey KJ (2003) Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation. Nature 421:384-388.
  • Wang H, Liao H, Ochani M, Justiniani M, Lin X, Yang L, Al-Abed Y, Wang H, Metz C, Miller EJ, Tracey KJ, Ulloa L (2004). Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med. 10:1216-21.
  • Huston JM, Ochani M, Rosas-Ballina M, Liao H, Ochani K, Pavlov VA, Gallowitsch-Puerta M, Ashok M, Czura CJ, Foxwell B, Tracey KJ, Ulloa L (2006). Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis. J Exp Med. 203:1623-8.
  • Pavlov VA, Ochani M, Gallowitsch-Puerta M, Ochani K, Huston JM, Czura CJ, Al-Abed Y, Tracey KJ (2006). Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia. Proc Natl Acad Sci U S A. 103:5219-23.
  • Tracey KJ (2007). Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest. 117:289-96.
  • Rosas-Ballina M, Ochani M, Parrish WR, Ochani K, Harris YT, Huston JM, Chavan S,. Tracey KJ (2008). The splenic nerve is required for cholinergic anti-inflammatory pathway control of TNF in endotoxemia. Proc Natl Acad Sci U S A., in press.
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