Tuesday, Sept. 26, 2006, 11:45 a.m. – 12:15 p.m.

Searle Center Lecture Hall

(with broadcast to Fitzpatrick CIEMAS lobby)

Classic neurotransmitters were easy to conceptualize, following the paradigm of acetylcholine, being stored in neuronal vesicles and acting on membrane receptors. Recent putative transmitters so change the model that the term ‘neurotransmitter’ seems obsolete.

 

Gases such as nitric oxide and carbon monoxide cannot be stored in vesicles nor act at membrane receptors. The D-isomer of serine is a transmitter which occurs in glia. Messengers regulating intracellular events of many cells, but especially neurons, are altering signaling conceptualizations. The inositol phosphate IP3 is well known to release intracellular calcium, but other inositol polyphosphates have unprecedented actions. Thus the energetic pyrophosphate IP7 physiologically phosphorylates protein targets and, unlike ATP, it appears to pyrophosphorylate them.

 

While nitric oxide signals physiologically, it also initiates a death cascade by nitrosylating the housekeeping glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) which acquires the capacity to bind to the ubiquitin-3-ligase Siah, enter the nucleus and kill cells, possibly by enhancing the protein acetylase activity of p300/CBP.

Dr. Snyder received his undergraduate and medical training at Georgetown University (MD 1962); Research Associate training with Julius Axelrod at the NIH (1963-1965); and psychiatric training at the Johns Hopkins Hospital (1965-1968). In 1966 he joined the faculty of the Johns Hopkins University School of Medicine as an Assistant Professor of Pharmacology. In 1968 he was named an Associate Professor of both Pharmacology and Psychiatry, and he became Professor in 1970. In 1980, he established the Department of Neuroscience and served as its Director until earlier this year (2006). He is presently Distinguished Service Professor of Neuroscience, Pharmacology and Psychiatry.

 

Many advances in molecular neuroscience have stemmed from Dr. Snyder's identification of receptors for neurotransmitters and drugs and elucidation of the actions of psychotropic agents. He pioneered the labeling of receptors by reversible ligand binding in the identification of opiate receptors and extended this technique to all the major neurotransmitter receptors in the brain. In characterizing each new group of receptors, he also elucidated actions of major neuroactive drugs. The isolation and subsequent cloning of receptor proteins stems from the ability to label, and thus monitor, receptors by using these ligand binding techniques.

 

Dr. Snyder is the recipient of numerous professional honors, including the Albert Lasker Award for Basic Biomedical Research (1978), the National Medal of Science (2005), the Wolf Foundation Prize in Medicine (1983), the Dickson Prize of the University of Pittsburgh (1983), the Bower Award of the Franklin Institute (1991), the Bristol-Myers Squibb Award for Distinguished Achievement in Neuroscience Research (1996) and the Gerard Prize of the Society for Neuroscience (2000). He has also been awarded numerous Honorary Doctor of Science degrees.

 

He is a member of the United States National Academy of Sciences and a Fellow of the American Academy of Arts and Sciences and the American Philosophical Society. He is the author of more than 1000 journal articles and several books including Uses of Marijuana (1971), Madness and the Brain (1974), The Troubled Mind (1976), Biological Aspects of Abnormal Behavior (1980), Drugs and the Brain (1986), and Brainstorming (1989).

 

The application of Dr. Snyder's techniques has enhanced the development of new agents in the pharmaceutical industry by enabling rapid screening of large numbers of candidate drugs. Dr. Snyder applied receptor techniques to elucidate intracellular messenger systems including isolation of inositol 1,4,5,-trisphosphate receptors and elucidation of inositol pyrophosphates as phosphorylating agents.

 

He has established gases as a new class of neurotransmitters, beginning with his demonstrating the role of nitric oxide in mediating glutamate synaptic transmission and neurotoxicity. His isolation and molecular cloning of nitric oxide synthase led to major insights into the neurotransmitter functions of nitric oxide throughout the body. Subsequently, he established carbon monoxide as another gaseous transmitter and D-serine as a glial derived endogenous ligand of glutamate-NMDA receptors.

 

He also has discovered novel mechanisms of cell death involving a nitric oxide-glyceraldehyde-3-phosphate dehydrogenase-Siah pathway as well as an IP3-cytochrome C-calcium cascade.