Kevin J. Tracey
Encyclopedia
Kevin J. Tracey, a scientist and inventor, was born in Fort Wayne, Indiana
on 10 December 1957. He is President of the Feinstein Institute for Medical Research and Professor and President of the Elmezzi Graduate School of Molecular Medicine in Manhasset, New York.
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
under Prof. Russel Patterson. During this time he was also a guest investigator at Rockefeller University
.
, in Manhasset, New York, where he practiced neurosurgery and established the Laboratory of Biomedical Science. In 2005 he was appointed President of the Feinstein Institute for Medical Research, and Professor and President of the Elmezzi Graduate School of Molecular Medicine in Manhasset, New York. In 2008 ]North Shore LIJ partnered with Hofstra University to establish a new School of Medicine at Hofstra University
.
, and mechanisms of neural signaling that control immune responses. In the early 1980's, he and colleagues described the direct inflammatory activity of tumor necrosis factor-alpha (TNF). This was followed by the first report that monoclonal antibodies against TNF can be effectively used as a therapeutic agent. As confirmed by an expanding field of research, TNF is a mediator of septic shock, but not sepsis. This prompted Tracey to search for another putative mediator of sepsis, culminating in 1999 by the identification of HMGB1
, a protein previously known as a DNA-binding transcription factor, as an inflammatory mediator and drug target.
Reasoning that evolution conferred protective mechanisms to prevent the unrestrained release of TNF and HMGB1, and that the nervous system provides crucial homeostatic control on oragn phsyiology, Tracey proposed a mechanism for the neural control of TNF and HMGB1. Termed the "Inflammatory reflex
", action potentials carried in the vagus nerve regulate cytokine release and innate immunity. The neurophysiological mechanism is that action potentials transmitted in the vagus nerve activate the release of acetylcholine
, a neurotransmitter
, that interacts with alpha-7 nicotinic receptor
s expressed on the cell surface of macrophages that produce TNF and other cytokines. The interaction of acetylcholine with alpha-7 nicotinic receptors prevents cytokine release by downregulating nuclear activation of NFkB. Stimulating the vagus nerve signals inhibits potentially damaging cytokine responses, and protect against organ damage caused by unregulated or excessive cytokine release. In 2011 he and his colleagues discovered a T cell subset that secretes acetylcholine in the spleen when activated by signals arising in the vagus nerve. These cells are regulated by incoming neurotransmission arising in the brain stem, and respond by producing the terminal neurotransmitter required to complete the Inflammatory Reflex. The neural circuit may be exploited to therapeutic advantage, because application of electrodes to stimulate the vagus nerve (vagus nerve stimulation
) protects against damaging inflammation in experimental arthritis, colitis, ischemia, myocardial infarction, congestive heart failure, and other conditions. The importance of the inflammatory reflex in controlling inflammation establishes the concept that the immune system does not function autonomously, but rather its output is coordinated by physiological units of reflex action.
, and severe sepsis.
Fort Wayne, Indiana
Fort Wayne is a city in the US state of Indiana and the county seat of Allen County. The population was 253,691 at the 2010 Census making it the 74th largest city in the United States and the second largest in Indiana...
on 10 December 1957. He is President of the Feinstein Institute for Medical Research and Professor and President of the Elmezzi Graduate School of Molecular Medicine in Manhasset, New York.
Education
Kevin J. Tracey received his B.S. in Chemistry from Boston CollegeBoston College
Boston College is a private Jesuit research university located in the village of Chestnut Hill, Massachusetts, USA. The main campus is bisected by the border between the cities of Boston and Newton. It has 9,200 full-time undergraduates and 4,000 graduate students. Its name reflects its early...
in 1979 and his M.D. from Boston University
Boston University
Boston University is a private research university located in Boston, Massachusetts. With more than 4,000 faculty members and more than 31,000 students, Boston University is one of the largest private universities in the United States and one of Boston's largest employers...
in 1983. From 1983 to 1992 he trained in neurosurgery at the New York Hospital
New York Hospital
New York Hospital or “Old New York Hospital” or “City Hospital” was the oldest hospital in New York City and the second oldest hospital in the United States.-Early History:...
/Cornell University
Cornell University
Cornell University is an Ivy League university located in Ithaca, New York, United States. It is a private land-grant university, receiving annual funding from the State of New York for certain educational missions...
under Prof. Russel Patterson. During this time he was also a guest investigator at Rockefeller University
Rockefeller University
The Rockefeller University is a private university offering postgraduate and postdoctoral education. It has a strong concentration in the biological sciences. It is also known for producing numerous Nobel laureates...
.
Academic appointments
In 1992, Tracey moved to the North Shore-LIJ Health SystemNorth Shore-LIJ Health System
The North Shore-Long Island Jewish Health System was founded in 1997 with the merger of the North Shore Health System and LIJ Medical Center, creating a healthcare network that now includes 15 hospitals , The Feinstein Institute for Medical Research, rehabilitation and skilled nursing facilities, ...
, in Manhasset, New York, where he practiced neurosurgery and established the Laboratory of Biomedical Science. In 2005 he was appointed President of the Feinstein Institute for Medical Research, and Professor and President of the Elmezzi Graduate School of Molecular Medicine in Manhasset, New York. In 2008 ]North Shore LIJ partnered with Hofstra University to establish a new School of Medicine at Hofstra University
Hofstra University
Hofstra University is a private, nonsectarian institution of higher learning located in the Village of Hempstead, New York, United States, about east of New York City: less than an hour away by train or car...
.
Principal scientific contributions
Tracey studies the molecular basis of inflammationInflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
, and mechanisms of neural signaling that control immune responses. In the early 1980's, he and colleagues described the direct inflammatory activity of tumor necrosis factor-alpha (TNF). This was followed by the first report that monoclonal antibodies against TNF can be effectively used as a therapeutic agent. As confirmed by an expanding field of research, TNF is a mediator of septic shock, but not sepsis. This prompted Tracey to search for another putative mediator of sepsis, culminating in 1999 by the identification of HMGB1
HMGB1
High-mobility group protein B1, also known as high-mobility group protein 1 and amphoterin, is a protein that in humans is encoded by the HMGB1 gene.HMG-1 belongs to high mobility group.-Role in Inflammation:...
, a protein previously known as a DNA-binding transcription factor, as an inflammatory mediator and drug target.
Reasoning that evolution conferred protective mechanisms to prevent the unrestrained release of TNF and HMGB1, and that the nervous system provides crucial homeostatic control on oragn phsyiology, Tracey proposed a mechanism for the neural control of TNF and HMGB1. Termed the "Inflammatory reflex
Inflammatory reflex
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...
", action potentials carried in the vagus nerve regulate cytokine release and innate immunity. The neurophysiological mechanism is that action potentials transmitted in the vagus nerve activate the release of acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
, a neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
, that interacts with alpha-7 nicotinic receptor
Alpha-7 nicotinic receptor
The alpha-7 nicotinic receptor, also known as the α7 receptor, is a type of nicotinic acetylcholine receptor, consisting entirely of α7 subunits....
s expressed on the cell surface of macrophages that produce TNF and other cytokines. The interaction of acetylcholine with alpha-7 nicotinic receptors prevents cytokine release by downregulating nuclear activation of NFkB. Stimulating the vagus nerve signals inhibits potentially damaging cytokine responses, and protect against organ damage caused by unregulated or excessive cytokine release. In 2011 he and his colleagues discovered a T cell subset that secretes acetylcholine in the spleen when activated by signals arising in the vagus nerve. These cells are regulated by incoming neurotransmission arising in the brain stem, and respond by producing the terminal neurotransmitter required to complete the Inflammatory Reflex. The neural circuit may be exploited to therapeutic advantage, because application of electrodes to stimulate the vagus nerve (vagus nerve stimulation
Vagus nerve stimulation
Vagus nerve stimulation is an adjunctive treatment for certain types of intractable epilepsy and treatment-resistant depression.- Mechanism of action :...
) protects against damaging inflammation in experimental arthritis, colitis, ischemia, myocardial infarction, congestive heart failure, and other conditions. The importance of the inflammatory reflex in controlling inflammation establishes the concept that the immune system does not function autonomously, but rather its output is coordinated by physiological units of reflex action.
Awards and honors
- Honorary doctorate from the Karolinska Institute in Stockholm, 2009
- Association of American PhysiciansAssociation of American PhysiciansThe Association of American Physicians is a medical society founded in 1885 by the Canadian physician Sir William Osler and six other distinguished physicians of his era, for "the advancement of scientific and practical medicine." Election to the AAP is an honor extended to individuals with...
, 2009 - DeWitt Stetten lectureship National Institutes of HealthNational Institutes of HealthThe National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
, 2007 - Annual Clinical Science Lectureship Karolinska Institute, 2002
- Invited lectureships at Harvard, YaleYALERapidMiner, formerly YALE , is an environment for machine learning, data mining, text mining, predictive analytics, and business analytics. It is used for research, education, training, rapid prototyping, application development, and industrial applications...
, The Rockefeller University, The Scripps Institute and the University of Texas Southwestern - Co-chair of the first international scientific congress addressing "The Inflammatory Reflex", a Nobel Symposium of the Karolinska Institute, 2004
- Co-chair of the "First HMGB1 Cytokine World Congress" in Saltsjöbaden, Sweden, in 2003
- Editor in Chief: Molecular MedicineMolecular Medicine (journal)Molecular Medicine is a peer-reviewed open access medical journal published by The Feinstein Institute for Medical Research. It was established in 1994 and is currently published in paper format six times annually. Manuscripts are posted online when they are accepted for publication...
, and Advisory Editor: Journal of Experimental MedicineJournal of Experimental MedicineThe Journal of Experimental Medicine is a peer-reviewed academic journal published by the Rockefeller University Press that publishes research papers and commentaries on the physiological, pathological, and molecular mechanisms that encompass the host response to disease... - American Society of Clinical Investigation (2001)
- Highly Cited Researcher in Immunology.
Book
Tracey's book Fatal Sequence: The Killer Within, recounts the course of a young patient with sepsis, a case that influenced Tracey's research into the molecular basis of septic shockSeptic shock
Septic shock is a medical emergency caused by decreased tissue perfusion and oxygen delivery as a result of severe infection and sepsis, though the microbe may be systemic or localized to a particular site. It can cause multiple organ dysfunction syndrome and death...
, and severe sepsis.
Multimedia
- "Physiology and Immunology of the Cholinergic Anti-Inflammatory Pathway" Stetten Lecture Videocast, October 24, 2007
- "Nervous System/Immune System Connection" Stetten Podcast Interview, November 2, 2007
- "The Inflammatory Reflex" Centricity Series Video Talk, December 17, 2007
- NIGMS, September 2010.
External links
- at The Feinstein Institute for Medical Research
- at Albert Einstein College of Medicine
- The Dana Foundation
- Scientific Publications – All publications of articles by Kevin J. Tracey listed in PubMed