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Solomon H. Snyder, D.Phil., D.Sc., M.D.

Photo of Dr. Solomon H. Snyder, D.Phil., D.Sc., M.D.

Professor of Neuroscience

Research Interests: Neurotransmitters, second messengers and drug action in the nervous system

Contact for Research Inquiries

Wood Basic Science Building
725 North Wolfe Street
Baltimore, MD 21205 map
Phone: 410-955-3024
Fax: 410-955-3623

Background

Dr. Solomon H. Snyder is a distinguished service professor of neuroscience, pharmacology and psychiatry at the Johns Hopkins University School of Medicine. He is the founder of the Solomon H. Snyder Department of Neuroscience and served as its director from 1980 to 2006. He is world-renowned for his pioneering research in the identification of receptors for neurotransmitters and drugs and the elucidation of the actions of psychotropic agents.

Dr. Snyder completed his undergraduate work at Georgetown College and received his M.D. from the Georgetown Medical School. After further studies at the National Institutes of Health, he completed a residency in psychiatry at Johns Hopkins. He joined the Johns Hopkins faculty in 1966.

Among dozens of professional and academic honors, Dr. Snyder has received the U.S. National Academy of Science Award in Neuroscience, the Albany Prize in Medicine, the National Medal of Science, the Wolf Foundation Prize in Medicine and the Albert Lasker Award for Basic Biomedical Research. He holds Honorary Doctor of Science degrees from Northwestern University, Georgetown University, Ben Gurion University and the University of Maryland, among others.

Over the course of his distinguished career, he has authored or co-authored more than 1,000 peer-reviewed publications and seven books. He currently serves as Associate Editor of the Proceedings of the National Academy of Sciences of the U.S., and is a member of the United States National Academy of Sciences and a Fellow of the American Philosophical Society and the American Academy of Arts and Sciences.

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Titles

  • Professor of Neuroscience
  • Professor of Pharmacology and Molecular Sciences
  • Professor of Psychiatry and Behavioral Sciences

Education

Degrees

  • M.D., Georgetown University School of Medicine - Washington (District of Columbia) (1962)

Additional Training

Johns Hopkins University School of Medicine, Baltimore, MD, 1968, Residency in Psychiatry; National Institute of Mental Health, Bethesda, MD, 1965, Research Associate

Research & Publications

Research Summary

The Snyder lab is interested in atypical neurotransmitters such as the gasotransmitters nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S). Particular attention has been focused upon downstream targets of NO and H2S and the role of sulfhydration of the protein parkin in the pathophysiology of Parkinson’s disease. Additionally, the lab showed that Deprenyl, a drug used to treat Parkinson’s disease, acts by blocking the nitrosylation of GAPDH and its binding to Siah. Deprenyl-like drugs may be therapeutic in neurologic diseases and cocaine addiction.

The lab discovered that the striatal selectivity in Huntington’s Disease reflects the binding of the striatal-selective G protein Rhes to mutant huntingtin whose cytotoxicity arises from its inhibiting the promoter of the biosynthetic enzyme for H2S.

The lab has established that D-serine is a novel neurotransmitter, which acts by stimulating the “glycine” site of glutamate-NMDA receptors. The lab isolated and cloned serine racemase, which generates D- from L-serine. The pathophysiology of DISC1, whose mutation underlies psychotic disorders, reflects its binding to serine racemase to impair D-serine formation.

The lab has also identified, isolated and elucidated receptors for the second messenger IP3, which releases intracellular calcium. They have cloned a family of three IP6 kinases and a related enzyme, inositol polyphosphate multikinase (IPMK). Besides phosphorylating inositol phosphates, IPMK is a physiologic PI3 kinase that can facilitate protein translation and play a major role in transcriptional signaling. The importance of these events is evident in the abolition of immediate early gene induction in IPMK deleted mice.

Lab

Neurotransmitters, second messengers and drug action in the nervous system

Information processing in the brain reflects communication among neurons via neurotransmitters. The major chemical classes of neurotransmitters are biogenic amines, amino acids and peptides. During the past few years we have identified and characterized novel transmitters or neuromodulators which overturn much dogma in the field. For instance, we discovered that nitric oxide (NO) satisfies the major criteria of a neurotransmitter, as NO synthase is localized to specific neuronal populations and inhibitors of the enzyme block neurotransmission in certain systems. Yet NO is a gas which cannot be stored in synaptic vesicles, released by exocytosis, or act at receptor proteins on cell membranes. In vascular stroke excess release of the excitatory amino acid neurotransmitter glutamate activates NO synthase to form NO that mediates neurotoxicity. Evidence for this includes the blockade of stroke damage by inhibitors of NO synthase and a lesser amount of stroke damage in the brains of mice lacking the neuronal form of NO synthase. In mice in which the gene for the neuronal NO synthase has been "knocked out" we observe dramatic alterations in social and sexual behavior indicating a prominent role for NO in aggression and sexual attraction.

At least one other gas, carbon monoxide (CO) may be a neurotransmitter. CO is formed by the action of the enzyme heme oxygenase, which cleaves the heme ring liberating CO and forming biliverdin, which is converted to bilirubin. We found that a neuronal form of heme oxygenase occurs in discrete neuronal populations in the brain, and CO formed from it may be involved in regulating levels of cyclic GMP. Just as NO, formed in the endothelial layer of blood vessels, diffuses to the smooth muscle and is a major normal relaxing element of blood vessels, CO is formed by heme oxygenase in the endothelium and also relaxes blood vessels. Besides forming CO, heme oxygenase action gives rise to ferrous iron and biliverdin which is rapidly reduced to bilirubin. We have shown that bilirubin is a key neuronal antioxidant neuroprotectant. Low nanomolar concentrations of bilirubin reverse the oxidant effects of 10,000 times higher concentrations of oxidants, an amplification mediated by a unique bilverdin reductase cycle. When bilirubin acts as an antioxidant, it is oxidized to biliverdin. Biliverdin reductase rapidly reforms bilirubin. Deletion of biliverdin reductase from cells leads to excess oxidation and cell death.

D-serine may be a neurotransmitter, as improbable as the gases, being the "wrong" isomer and occurring in glia, not neurons. Levels of D-serine in the brain are a third those of L-serine, and it is the only D-amino acid to occur in substantial levels in the brain. Our immunohistochemical maps reveal D-serine in a unique population of glia, which ensheathe nerve terminals selectively in regions of the brain enriched in the subtype of glutamate receptor referred to as the N-methyl-D-aspartate (NMDA) receptor. NMDA receptors had been thought to be co-activated by the amino acids glycine and glutamate. D-Serine appears to be the normal stimulus for the glycine site of this receptor. D-Serine is released from these astrocytes by glutamate acting at the AMPA subtype of receptor. Selective destruction of D-serine by D-amino acid oxidase markedly reduces NMDA neurotransmission. A novel enzyme, serine racemase, transforms L- to D-serine. It binds to GRIP, a scaffolding protein that links serine racemase to AMPA receptors so that glutamate transmission markedly activate the enzyme with associated release of D-serine (Figure 1: Diagram of nitric oxide (NO) and carbon monoxide (CO) disposition at synapses).

These two substances have been characterized in our laboratory as atypical neurotransmitters. As gases, they cannot be stored in synaptic vesicles, released by exocytosis or bind to receptor proteins on the external surface of neurons. They are formed "on demand" by activation of their biosynthetic enzymes. Neuronal depolarization leads to calcium influx that binds to calmodulin, stimulating NO synthase as well as heme oxygenase-9. Both NO and CO diffuse into adjacent cells to activate guanylyl cyclase to form cyclic GMP. Additionally, NO S-nitrosylates a wide range of proteins.

Lab Website: Solomon Snyder Laboratory

Selected Publications

View all on Pubmed

  1. Sen N, Paul BD, Gadalla MM, Mustafa AK, Sen T, Xu R, Kim S, Snyder SH. (2012) "Hydrogen sulfide-linked sulfhydration of NF-κB mediates its antiapoptotic actions." Mol Cell 2012 Jan 13;45(1):13-24.
  2. Subramaniam S, Napolitano F, Mealer RG, Kim S, Errico F, Barrow R, Shahani N, Tyagi R, Snyder SH, Usiello A. (2011) "Rhes, a striatal-enriched small G protein, mediates mTOR signaling and L-DOPA-induced dyskinesia." Nat Neurosci 2011 Dec 18;15(2):191-3.
  3. Sen N, Snyder SH. (2011) "Neurotrophin-mediated degradation of histone methyltransferase by S-nitrosylation cascade regulates neuronal differentiation." Proc Natl Acad Sci USA 2011 Dec 13; 108(50):20178-83. Epub 2011 Nov 28.
  4. Chakraborty A, Kim S, Snyder SH. (2011) "Inositol pyrophosphates as mammalian cell signals." Sci Signal 2011 Aug 23; 4(188):re1.
  5. Kim S, Kim SF, Maag D, Maxwell MJ, Resnick AC, Juluri KR, Chakraborty A, Koldobskiy MA, Cha SH, Barrow R, Snowman AM, Snyder SH. (2011) "Amino acid signaling to mTOR mediated by inositol polyphosphate multikinase." Cell Metab 2011 Feb 2; 13(2)215-21.
  6. Kornberg MD, Sen N, Hara MR, Juluri KR, Nguyen JV, Snowman AM, Law L, Hester LD, Snyder SH. (2010) "GAPDH mediates nitrosylation of nuclear proteins." Nat Cell Biol 2010 Nov;12(11):1094-100. Epub 2010 Oct 24.
  7. Chakraborty A, Koldobskiy MA, Bello NT, Maxwell M, Potter JJ, Juluri KR, Maag D, Kim S, Huang AS, Dailey MJ, Saleh M, Snowman AM, Moran TH, Mezey E, Snyder SH. (2010) "Inositol pyrophosphates inhibit Akt signaling, thereby regulating insulin sensitivity and weight gain." Cell 2010 Dec 10;143(6):897-910.
  8. Mustafa AK, Gadalla MM, Sen N, Kim S, Mu W, Gazi SK, Barrow RK, Yang G, Wang R, Snyder SH. (2009) "H2S signals through protein S-sulfydration." Sci Signal 2009 Nov 10;2(96):ra72.
  9. Subramaniam S, Sixt KM, Barrow R, Snyder SH. (2009) "Rhes, a striatal specific protein, mediates mutant-huntingtin cytotoxicity." Science 2009 Jun 5;324(5932):1327-30.
  10. Yang G, Wu L, Jiang B, Yang W, Qi J, Cao K, Meng Q, Mustafa AK, Mu W Zhang S, Snyder SH, Wang R. (2008) "H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase." Science 2008 Oct 24;322(5901):587-90.
  11. Kim SF, Huri DA, Snyder SH. (2005) "Inducible nitric oxide synthase binds, s-nitrosylates, and activates cyclooxygenase-2." Science 2005 Dec 23;310(5756):1966-70.
  12. Hara MR, Agrawal N, Kim SF, Cascio MB, Fujimuro M, Ozeki Y, Takahashi M, Cheah JH, Tankou SK, Hester LD, Ferris CD, Hayward SD, Snyder SH, Sawa A. (2005) "S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding." Nat Cell Biol 2005 Jul;7(7):665-74.
  13. van Rossum DB, Patterson RL, Sharma S, Barrow RK, Kornberg M, Gill DL, Snyder SH. (2005) "Phospholipase Cg1 controls surface expression of TRPC3 through an intermolecular PH domain." Nature 2005 Mar 3;434:99-104.
  14. Saiardi A, Bhandari R, Resnick AC, Snowman AM, Snyder SH. (2004) "Phosphorylation of proteins by inositol pyrophosphates." Science 2004 Dec 17;306(5704):2101-5.

Academic Affiliations & Courses

Graduate Program Affiliation

BCMB Program
Cellular and Molecular Medicine Graduate Program
Neuroscience Graduate Program
Pharmacology Graduate Program

Activities & Honors

Honors

  • Einstein Award for Research in Psychiatry and Related Disciplines, Albert Einstein College of Medicine of Yeshiva University, 1984
  • Baxter Award, American Association of Medical Colleges, 1995
  • Julius Axelrod Mentorship Award, American College of Neuropsychopharmacology, 2005
  • Daniel H. Efron Award, American College of Neuropsychopharmacology, 1974
  • Stanley Dean Award, American College of Psychiatrists, 1978
  • Scientific Achievement Award, American Medical Association, 1985
  • Judd Marmor Prize, American Psychiatric Association, 2000
  • Distinguished Service Award, American Psychiatric Association, 1989
  • Special Presidential Commendation, American Psychiatric Association, 1985
  • Hofheimer Award, American Psychiatric Association, 1972
  • Goodman and Gilman Award, American Society for Pharmacology and Experimental Therapeutics, 1980
  • John Jacob Abel Award, American Society for Pharmacology and Experimental Therapeutics, 1970
  • Distinguished Research Award, Association for Research in Nervous and Mental Disease, 1978
  • Edward J. Sachar Memorial Award, Columbia University, 1986
  • Van Dyke Award, Columbia University, 1978
  • Van Giesen Award, Columbia University, 1977
  • Joseph Priestley Prize, Dickinson College, 1992
  • Vittorio Erspamer Award, FIDIA Research Foundation, 1990
  • Sense of Smell Award, Fragrance Research Fund, 1987
  • Bower Award, Franklin Institute, 1992
  • Sarnat Award, Institute of Medicine, 2001
  • Goldman-Rakic Award, National Alliance for Research on Schizophrenia and Depression, 2002
  • Lieber Prize, National Alliance for Research on Schizophrenia and Depression, 2001
  • Salmon Prize, New York Academy of Medicine, 2001
  • National Institute on Drug Abuse, Research Pacesetter Award, 1977
  • Taylor Award, Roberts Institute, 1990
  • A.E. Bennett Award, Society for Biological Psychiatry, 1970
  • Ralph Gerard Prize, Society for Neuroscience, 2000
  • Edward Perl Award, University of North Carolina, 2007
  • Dickson Prize, University of Pittsburgh, 1983
  • Wolf Prize in Medicine, Wolf Foundation, 1983
  • Award in Neuroscience, US National Academy of Science , 2013
  • Albany Prize in Medicine, 2007
  • National Medal of Science, 2005
  • Achievement Award, Society for Biomolecular Screening , 2000
  • City of Medicine Award, 2000
  • Bristol-Myers Squibb Award for Distinguished Achievement in Neuroscience Research, 1996
  • Award for Biomedical Research, Pasarow Foundation , 1991
  • Camelback Humanitarian Award, 1985
  • Ciba-Geigy Drew Award in Biomedical Research, 1985
  • Taylor Manor Award, 1981
  • Anna Monica Award in Biological Psychiatry, 1979
  • Albert Lasker Medical Research Award for Basic Biomedical Research, 1978
  • Outstanding Young Scientist, Maryland Academy of Sciences , 1969

Memberships

  • American Academy of Arts and Sciences
    Fellow
  • American Philosophical Society
    Fellow
  • Institute of Medicine
    Fellow
  • Neuroscience Research Program
    Associate
  • U.S. National Academy of Sciences
    Member

Professional Activities

  • Associate Editor, Proceedings of the National Academy of Sciences
  • Board, Peabody Conservatory, 2005
  • Board, Foundation for the NIH, 1994
  • Board, Shriver Hall Concert Series, 1994
  • Board, Baltimore Symphony Orchestra, 1992
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