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Gary Rudnick, PhD

Professor Emeritus of Pharmacology
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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

Education & Training

PhD
Brandeis University (1974)
BS
Antioch College, Chemistry (1968)
Postdoc
Roche Institute of Molecular Biology

Research

Overview

We are studying the conformational changes that transport proteins undergo in moving their substrates across biological membranes.

Part of this work focuses on identifying the parts of neurotransmitter transporters (particularly serotonin transporter) that interact with substrates and ions.

We are also examining bacterial homologues of neurotransmitter transporters as model systems for understanding the mechanistic principles of transport.

Another area of research is the regulation of serotonin transport by cyclic GMP, which is defective in some individuals carrying mutant forms of the transporter and is associated with several psychiatric disorders.


The Rudnick Lab has closed down subsequent to Professor Rudnick transitioning to emeritus status.

Medical Subject Headings (MeSH)

Biochemistry; Neurobiology; Neurochemistry; Neuropharmacology

Research at a Glance

Yale Co-Authors

Frequent collaborators of Gary Rudnick's published research.

Publications

2024

2023

2019

2018

2017

2016

2015

Get In Touch

Contacts

Academic Office Number
Lab Number
Office Fax Number
Mailing Address

Pharmacology

PO Box 208066, 333 Cedar Street

New Haven, CT 06520-8066

United States

Administrative Support

Locations

  • Rudnick Lab

    Lab

    Sterling Hall of Medicine, B-Wing

    333 Cedar Street, Ste B334

    New Haven, CT 06510

    Appointments

    203.785.4547