# 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 the Zucker School of Medicine, and president of the Elmezzi Graduate School of Molecular Medicine 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.

## 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 with Russel Patterson. During this time he was also a guest investigator at Rockefeller University.

## Academic appointments

In 1992, Tracey moved to Northwell Health, 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).

## Research

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. Training as both a neurosurgeon and immunologist merged in discovery of the mechanism by which neurons control the immune system.
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. 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. 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. 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.
In the 1990s an accidental result in the Tracey lab led to a discovery of how the brain normally inhibits the production of TNF. They had developed an anti-inflammatory named CNI-1493, or semapimod. Unexpectedly, the CNI-1493 stimulated the vagus nerve to inhibit TNF production in the body. 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".
In 2007 he co-founded a company called SetPoint Medical which aimed to develop vagus nerve stimulation devices to treat autoimmune diseases. The company started clinical trials in 2011, and in 2016 published results for treating patients with rheumatoid arthritis. Vagus nerve stimulation has successfully blocked inflammation in clinical trials of rheumatoid arthritis and inflammatory bowel disease.
The Tracey lab mapped the inflammatory reflex using genetic, immunological, and bioelectronic tools to define the molecular and neuroscience mechanisms. An unexpected finding from this work is the vagus nerve, a parasympathetic nerve, controls the splenic nerve, a sympathetic nerve. 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. These regulatory T cells produce acetylcholine, the chemical signal to macrophages which turns off production of TNF and other inflammatory mediators.
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. 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.
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.

## Awards and honors

* Hans Wigzell Research Foundation's Science Prize, 2023
* Crain's Business New York "Most Notable Leaders in Healthcare, 2023
* Fellow, American Institute for Medical and Biological Engineering, 2020
* Harvey Lecture Series, Harvey Society, 2018
* Fellow, American Association for the Advancement of Science, 2015
* Grenvik lectureship, University of Pittsburgh, 2013
* Member, Association of American Physicians, 2009
* Nancy Bucher lecture, Boston University School of Medicine, 2009
* Honorary doctorate from the Karolinska Institute, 2009
* Highly Cited Researcher in Immunology.
* DeWitt Stetten Jr. lectureship, National Institute of Health, 2007
* Member, American Society of Clinical Investigation, 2001
* Recognized as one of the most cited researchers, listed among the top 1,000 worldwide, PLOS Biology, The Public Library of Science Magazine

## Select publications

| Year | Title | Publication | Author(s) | Volume/Issue Citation |
| 2024 | Consolidating roles of neuroimmune reflexes: specificity of afferent, central, and efferent signals in homeostatic immune networks | Cold Spring Harbor Laboratory Press | Kevin J. Tracey | 0.1101/gad.352287.124 |
| 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

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