Gary Rudnick, PhD
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About
Titles
Professor Emeritus of Pharmacology
Biography
Professor Rudnick is a graduate of Antioch College, where he received a B.S. in Chemistry in 1968. He performed graduate studies in the enzymology of amino acid racemases in the laboratory of Robert H. Abeles in the Graduate Department of Biochemistry at Brandeis University, receiving a Ph.D. in Biochemistry in 1974. His graduate studies led to an understanding of the structure and mechanism of proline racemase that was confirmed by the crystal structure of a homologous protein in 2006. From 1973-1975, Professor Rudnick performed postdoctoral research on lactose permease with H. Ronald Kaback at the Roche Institute of Molecular Biology. This work provided a greater understanding of binding and transport reactions using photoaffinity reagents and substrate analogs. In 1975, he left Roche to become an Assistant Professor in the Department of Pharmacology at Yale, and was promoted to Associate Professor in 1980 and Professor in 1991.
Professor Rudnick’s research at Yale has focused on the mechanism and structure of mammalian serotonin transporter (SERT). He developed a system of platelet plasma membrane vesicles with which to study the bioenergetics and mechanism of transport. These studies provided an understanding of the coupling of ion gradients to serotonin accumulation and also identified SERT as the molecular target for the antidepressant imipramine and the psychostimulant MDMA (ecstasy).
Beginning in the 1990s, Professor Rudnick’s laboratory has been studying the molecular characteristics of SERT and other neurotransmitter transporters expressed in cultured cells. These studies led to the identification of the serotonin binding site in SERT and of regions in the protein undergoing conformational changes during transport. The availability of a crystal structure for a homologous bacterial transporter in 2005 allowed Professor Rudnick and his colleagues to use the conformational changes to propose a conformational mechanism of transport that is gaining wide acceptance. Because SERT is structurally related to many other transporters, the proposed mechanism is likely to apply to transporters functioning in many diverse biological systems.
In addition to these mechanistic studies, Professor Rudnick’s laboratory has been investigating a spontaneously occurring SERT mutant associated with several psychiatric disorders. The mutation apparently inhibits removal of a phosphate group added to SERT by cGMP-dependent protein kinase. The mechanism by which this phosphate increases SERT activity is an active area of investigation.
Appointments
Pharmacology
EmeritusPrimary
Other Departments & Organizations
Education & Training
- PhD
- Brandeis University (1974)
- BS
- Antioch College, Chemistry (1968)
- Postdoc
- Roche Institute of Molecular Biology
Research
Links & Media
Media
The substrate binding site of LeuT
Substrate binding in LeuT creates a network including Tyr-108, the substrate carboxyl group and a sodium ion bound at the Na1 site. This interaction activates closing of the extracellular pathway, an essential step in transport.
News
- May 02, 2023Source: YaleNews
Study Identifies Compounds That Ease Depression, Opioid Withdrawal in Mice
- November 28, 2018Source: Aarhus University
Aarhus University names Gary Rudnick Honorary Skou Professor
- October 24, 2016Source: Yale Medicine
A Yale pharmacologist pursues the therapeutic potential of a psychedelic drug
- September 30, 2016
A Yale pharmacologist pursues the therapeutic potential of a psychedelic drug
Get In Touch
Contacts
Pharmacology
PO Box 208066, 333 Cedar Street
New Haven, CT 06520-8066
United States
Locations
Rudnick Lab
Lab