Gary Rudnick, PhD

Professor of Pharmacology

Research Interests

Biochemistry; Neurobiology; Neurochemistry; Neuropharmacology

Research Organizations

Interdepartmental Neuroscience Program

Office of Cooperative Research

Research Summary

Our research concerns the proteins involved in neurotransmitter recycling responsible for the reuptake of serotonin and other biogenic amines. We are interested in how the structure of these proteins determines their ability to couple ion gradients to substrate transport. The transporters are responsible for the process that terminates the action of serotonin, norepinephrine, and dopamine released into the synaptic cleft. They are targets for antidepressant drugs like fluoxetine (Prozac) and for stimulants such as cocaine and amphetamines, such as MDMA (ecstasy). Current efforts in the laboratory include the identification of the pathway by which serotonin passes through the membrane, including residues that are involved in substrate and inhibitor binding and those involved in conformational changes that accompany transport. We are also studying the regulation of serotonin transporter activity by phosphorylation, and we are investigating bacterial homologues of the neurotransmitter transporter family for insights into the structure of these proteins.

Extensive Research Description

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.

Selected Publications

Full List of PubMed Publications

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Contact Info

Gary Rudnick, PhD
Lab Location
Rudnick LabSterling Hall of Medicine, B-Wing
333 Cedar Street, Ste B334

New Haven, CT 06510
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Mailing Address
PharmacologyPO Box 208066
333 Cedar Street

New Haven, CT 06520-8066

Curriculum Vitae

Rudnick Lab

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.