Kevin J. Tracey

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Kevin J. Tracey
Kevin J. Tracey Headshot.jpg
Tracey in 2019
Born (1957-12-10) 10 December 1957 (age 66)
Fort Wayne, Indiana
Alma mater Boston University
Known forBioelectronic Medicine
Scientific career
Fields Neurosurgery, immunology
Institutions Feinstein Institute for Medical Research
Website feinstein.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]

Contents

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.[ citation needed ]

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 an 11-month-old girl 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 as a cytokine capable of causing shock and tissue injury. [7] 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. [8] 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. [8]

In the 1990s 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 to inhibit TNF production in the body. [5] 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". [9] [10] [11]

In 2007 he co-founded a company called SetPoint Medical which aimed to develop vagus nerve stimulation devices to treat autoimmune diseases. [9] [12] [10] The company started clinical trials in 2011, and in 2016 published results for treating patients with rheumatoid arthritis. [9] Vagus nerve stimulation has successfully blocked inflammation in clinical trials of rheumatoid arthritis and inflammatory bowel disease. [13]

The Tracey lab mapped the inflammatory reflex using genetic, immunological, and bioelectronic tools to define the molecular and neuroscience mechanisms. [8] An unexpected finding from this work is the vagus nerve, a parasympathetic nerve, controls the splenic nerve, a sympathetic nerve. [14] 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. [14] These regulatory T cells produce acetylcholine, the chemical signal to macrophages which turns off production of TNF and other inflammatory mediators. [14]

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. [15] 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. [16]

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. [17]

Awards and honors

Select publications

YearTitle [28] PublicationAuthor(s)Volume/Issue Citation
2022Identification of a brainstem locus that inhibits tumor necrosis factorPNASKressel 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 KJ10.1073/pnas.2008213117
2016Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritisPNASKoopman FA, Chavan SS, Miljko S, Grazio S, Sokolovic S, Schuurman PR, Mehta AD, Levine YA, Faltys M, Zitnik R, Tracey KJ, Tak PP10.1073/pnas.1605635113
2011Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuitScienceRosas-Ballina M, Olofsson PS, Ochani M, Valdés-Ferrer SI, Levine YA, Reardon C, Tusche MW, Pavlov VA, Andersson U, Chavan S, Mak TW, Tracey KJ10.1126/science.1209985
2003Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammationNatureWang 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 KJ10.1038/nature01339
2002The inflammatory reflexNatureTracey KJ10.1038/nature01321
2000Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxinNatureBorovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ10.1038/35013070
1999HMG-1 as a late mediator of endotoxin lethality in miceScienceWang 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 KJ10.1126/science.285.5425.248

Book and editorial activities

Related Research Articles

<span class="mw-page-title-main">Vagus nerve</span> Cranial nerve X, for visceral innervation

The vagus nerve, also known as the tenth cranial nerve, cranial nerve X, or simply CN X, is a cranial nerve that carries sensory fibers that create a pathway that interfaces with the parasympathetic control of the heart, lungs, and digestive tract. It comprises two nerves—the left and right vagus nerves—but they are typically referred to collectively as a single subsystem. The vagus is the longest nerve of the autonomic nervous system in the human body and comprises both sensory and motor fibers. The sensory fibers originate from neurons of the nodose ganglion, whereas the motor fibers come from neurons of the dorsal motor nucleus of the vagus and the nucleus ambiguus. The vagus was also historically called the pneumogastric nerve.

<span class="mw-page-title-main">Autonomic nervous system</span> Division of the nervous system supplying internal organs, smooth muscle and glands

The autonomic nervous system (ANS), formerly referred to as the vegetative nervous system, is a division of the nervous system that operates internal organs, smooth muscle and glands. The autonomic nervous system is a control system that acts largely unconsciously and regulates bodily functions, such as the heart rate, its force of contraction, digestion, respiratory rate, pupillary response, urination, and sexual arousal. This system is the primary mechanism in control of the fight-or-flight response.

<span class="mw-page-title-main">Macrophage</span> Type of white blood cell

Macrophages are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris, and foreign substances, which do not have proteins that are specific to healthy body cells on their surface. This process is called phagocytosis, which acts to defend the host against infection and injury.

<span class="mw-page-title-main">Parasympathetic nervous system</span> Division of the autonomic nervous system

The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of the autonomic nervous system, and sometimes considered an independent system.

<span class="mw-page-title-main">Tumor necrosis factor</span> Protein

Tumor necrosis factor is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homologous TNF domain.

Psychoneuroimmunology (PNI), also referred to as psychoendoneuroimmunology (PENI) or psychoneuroendocrinoimmunology (PNEI), is the study of the interaction between psychological processes and the nervous and immune systems of the human body. It is a subfield of psychosomatic medicine. PNI takes an interdisciplinary approach, incorporating psychology, neuroscience, immunology, physiology, genetics, pharmacology, molecular biology, psychiatry, behavioral medicine, infectious diseases, endocrinology, and rheumatology.

<span class="mw-page-title-main">Innate immune system</span> One of the two main immunity strategies

The innate, or nonspecific, immune system is one of the two main immunity strategies in vertebrates. The innate immune system is an alternate defense strategy and is the dominant immune system response found in plants, fungi, prokaryotes, and invertebrates.

Neuroimmunology is a field combining neuroscience, the study of the nervous system, and immunology, the study of the immune system. Neuroimmunologists seek to better understand the interactions of these two complex systems during development, homeostasis, and response to injuries. A long-term goal of this rapidly developing research area is to further develop our understanding of the pathology of certain neurological diseases, some of which have no clear etiology. In doing so, neuroimmunology contributes to development of new pharmacological treatments for several neurological conditions. Many types of interactions involve both the nervous and immune systems including the physiological functioning of the two systems in health and disease, malfunction of either and or both systems that leads to disorders, and the physical, chemical, and environmental stressors that affect the two systems on a daily basis.

<span class="mw-page-title-main">Neuroimmune system</span>

The neuroimmune system is a system of structures and processes involving the biochemical and electrophysiological interactions between the nervous system and immune system which protect neurons from pathogens. It serves to protect neurons against disease by maintaining selectively permeable barriers, mediating neuroinflammation and wound healing in damaged neurons, and mobilizing host defenses against pathogens.

<span class="mw-page-title-main">CD137</span> Member of the tumor necrosis factor (TNF) receptor family

CD137, a member of the tumor necrosis factor (TNF) receptor family, is a type 1 transmembrane protein, expressed on surfaces of leukocytes and non-immune cells. Its alternative names are tumor necrosis factor receptor superfamily member 9 (TNFRSF9), 4-1BB, and induced by lymphocyte activation (ILA). It is of interest to immunologists as a co-stimulatory immune checkpoint molecule, and as a potential target in cancer immunotherapy.

The cholinergic anti-inflammatory pathway regulates the innate immune response to injury, pathogens, and tissue ischemia. It is the efferent, or motor arm of the inflammatory reflex, the neural circuit that responds to and regulates the inflammatory response.

<span class="mw-page-title-main">Toll-like receptor 9</span> Protein-coding gene in the species Homo sapiens

Toll-like receptor 9 is a protein that in humans is encoded by the TLR9 gene. TLR9 has also been designated as CD289. It is a member of the toll-like receptor (TLR) family. TLR9 is an important receptor expressed in immune system cells including dendritic cells, macrophages, natural killer cells, and other antigen presenting cells. TLR9 is expressed on endosomes internalized from the plasma membrane, binds DNA, and triggers signaling cascades that lead to a pro-inflammatory cytokine response. Cancer, infection, and tissue damage can all modulate TLR9 expression and activation. TLR9 is also an important factor in autoimmune diseases, and there is active research into synthetic TLR9 agonists and antagonists that help regulate autoimmune inflammation.

<span class="mw-page-title-main">HMGB1</span> Mammalian protein found in Homo sapiens

High mobility group box 1 protein, also known as high-mobility group protein 1 (HMG-1) and amphoterin, is a protein that in humans is encoded by the HMGB1 gene.

Damage-associated molecular patterns (DAMPs) are molecules within cells that are a component of the innate immune response released from damaged or dying cells due to trauma or an infection by a pathogen. They are also known as danger signals, and alarmins because they serve as warning signs to alert the organism to any damage or infection to its cells. DAMPs are endogenous danger signals that are discharged to the extracellular space in response to damage to the cell from mechanical trauma or a pathogen. Once a DAMP is released from the cell, it promotes a noninfectious inflammatory response by binding to a pattern recognition receptor. Inflammation is a key aspect of the innate immune response; it is used to help mitigate future damage to the organism by removing harmful invaders from the affected area and start the healing process. As an example, the cytokine IL-1α is a DAMP that originates within the nucleus of the cell which, once released to the extracellular space, binds to the PRR IL-1R, which in turn initiates an inflammatory response to the trauma or pathogen that initiated the release of IL-1α. In contrast to the noninfectious inflammatory response produced by DAMPs, pathogen-associated molecular patterns initiate and perpetuate the infectious pathogen-induced inflammatory response. Many DAMPs are nuclear or cytosolic proteins with defined intracellular function that are released outside the cell following tissue injury. This displacement from the intracellular space to the extracellular space moves the DAMPs from a reducing to an oxidizing environment, causing their functional denaturation, resulting in their loss of function. Outside of the aforementioned nuclear and cytosolic DAMPs, there are other DAMPs originated from different sources, such as mitochondria, granules, the extracellular matrix, the endoplasmic reticulum, and the plasma membrane.

Bioelectronics is a field of research in the convergence of biology and electronics.

An inflammatory cytokine or proinflammatory cytokine is a type of signaling molecule that is secreted from immune cells like helper T cells (Th) and macrophages, and certain other cell types that promote inflammation. They include interleukin-1 (IL-1), IL-6, IL-12, and IL-18, tumor necrosis factor alpha (TNF-α), interferon gamma (IFNγ), and granulocyte-macrophage colony stimulating factor (GM-CSF) and play an important role in mediating the innate immune response. Inflammatory cytokines are predominantly produced by and involved in the upregulation of inflammatory reactions.

The inflammatory reflex is a neural circuit that regulates the immune response to injury and invasion. All reflexes have an afferent and efferent arc. The Inflammatory reflex has a sensory afferent arc, which is activated by cytokines, and a motor or efferent arc, which transmits action potentials in the vagus nerve to suppress cytokine production. Increased signaling in the efferent arc inhibits inflammation and prevents organ damage.

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References

  1. 1 2 "Elmezzi Graduate School".
  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. ↑ "The Generator by Emily Anthes".
  5. 1 2 3 4 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. ↑ 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.
  8. 1 2 3 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.
  9. 1 2 3 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 logo PLoS transparent.svg
  10. 1 2 Behar, Michael (23 May 2014). "Can the Nervous System Be Hacked?". The New York Times.
  11. ↑ Finley, Allysia (22 July 2022). "Electricity Is the New Medical Miracle". The Wall Street Journal. Retrieved 25 August 2022.
  12. ↑ Garde, Damien (2013). "SetPoint Medical – 2013 Fierce 15". FierceBiotech.
  13. ↑ Waltz, Emily (14 June 2018). "Battling Crohn's Disease with Vagus Nerve Stimulation". Spectrum IEEE. Retrieved 23 February 2021.
  14. 1 2 3 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.
  15. ↑ Holme, Frida (May 2018). "Scientists Wants to Decode Body-Brain Nerve Signals to Diagnose Illness". Frontline Genomics.
  16. ↑ Zeller, Gregory (February 2019). "Tracey, Global Team Unearth New Bioelectronic Clue". InnovateLI.
  17. ↑ "Researchers Discover Possible Pathway of Vagus Nerve's Inflammatory Response". Pain Medicine News. Retrieved 9 June 2021.
  18. ↑ "AIMBE College of Fellows Class of 2020". AIMBE. American Institute for Medical and Biological Engineering. Retrieved 14 July 2022.
  19. ↑ "The Harvey Society: Lecture Series". The Harvey Society. Retrieved 6 February 2019.
  20. ↑ "Grenvik lectureship".
  21. ↑ "The Association of American Physicians". The Association of American Physicians. Retrieved 12 February 2019.
  22. ↑ "The Nancy L. R. Bucher Seminar Series". Boston University School of Medicine. Retrieved 12 February 2019.
  23. ↑ Maria Sjögren. "Honorary doctors at Karolinska Institutet 2009 – Prizes and Awards – Karolinska Institutet". Ki.se. Retrieved 7 February 2013.
  24. ↑ "ISI Highly Cited Researchers".
  25. ↑ "2007 Stetten Lecture – Physiology and Immunology of the Cholinergic Anti-inflammatory Pathway". NIH National Institute of General Medical Sciences. Retrieved 8 February 2019.
  26. ↑ "Member Directory". The American Society of Clinical Investigation. Retrieved 12 February 2019.
  27. ↑ 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.
  28. ↑ "Tracey KJ PubMed Publications" . Retrieved 2 November 2021.
  29. ↑ "Bioelectronic Medicine". Springer Nature. Retrieved 6 February 2019.
  30. ↑ "Journal of Experimental Medicine". Rockefeller University Press. Retrieved 6 February 2019.
  31. ↑ "Molecular Medicine Editorial Board". Springer Nature. Retrieved 6 February 2019.
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