Rudnick, Gary - Yale University - Biological & Biomedical Sciences

个人简介

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. PhD Brandeis University (1974) Postdoc Roche Institute of Molecular Biology

研究领域

Biochemistry; Neurobiology; Neurochemistry; Neuropharmacology

近期论文

查看导师新发文章（温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

Cyclic GMP-dependent stimulation of serotonin transport does not involve direct transporter phosphorylation by cGMP-dependent protein kinase. Wong A, Zhang YW, Jeschke GR, Turk BE, Rudnick G. Cyclic-GMP-dependent stimulation of serotonin transport does not involve direct transporter phosphorylation by cGMP-dependent protein kinase. J Biol Chem. 2012 Aug 31. [Epub ahead of print] The mechanistic basis for noncompetitive ibogaine inhibition of serotonin and dopamine transporters. Bulling S, Schicker K, Zhang YW, Steinkellner T, Stockner T, Gruber CW, Boehm S, Freissmuth M, Rudnick G, Sitte HH, Sandtner W. The mechanistic basis for noncompetitive ibogaine inhibition of serotonin and dopamine transporters. J. Biol. Chem. 2012;287(22):18524-34 Reconstructing a chloride binding site in a bacterial neurotransmitter transporter homologue. Tavoulari S., Rizwan, A.N., Forrest, L.R. and Rudnick G. Reconstructing a chloride binding site in a bacterial neurotransmitter transporter homologue. (2011) J Biol Chem 286: 2834-2842. Myristoylation of cGMP-dependent protein kinase dictates isoform specificity for serotonin transporter regulation. Zhang, Y-W and Rudnick, G. Myristoylation of cGMP-dependent protein kinase dictates isoform specificity for serotonin transporter regulation. (2011) J Biol Chem 286: 2461-2468. Ligand effects on cross-linking support a conformational mechanism for serotonin transport. Tao Z, Zhang YW, Agyiri A, Rudnick G. Ligand effects on cross-linking support a conformational mechanism for serotonin transport. JBC. 2009;284(49):33807-14. Fluoxetine (Prozac) binding to serotonin transporter is modulated by chloride and conformational changes. Tavoulari S, Forrest LR, Rudnick G. Fluoxetine (Prozac) binding to serotonin transporter is modulated by chloride and conformational changes. J Neurosci. 2009 Jul 29;29(30):9635-43. Mechanism for alternating access in neurotransmitter transporters. Forrest LR, Zhang YW, Jacobs MT, Gesmonde J, Xie L, Honig BH, Rudnick G. Mechanism for alternating access in neurotransmitter transporters. Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10338-43 Zhang YW, Turk BE, Rudnick G: Control of serotonin transporter phosphorylation by conformational state. Proc Natl Acad Sci U S A. 2016 May 17; 2016 May 2. PMID: 27140629 Tavoulari S, Margheritis E, Nagarajan A, DeWitt DC, Zhang YW, Rosado E, Ravera S, Rhoades E, Forrest LR, Rudnick G: Two Na+ Sites Control Conformational Change in a Neurotransmitter Transporter Homolog. J Biol Chem. 2016 Jan 15; 2015 Nov 18. PMID: 26582198 Sandtner W, Stockner T, Hasenhuetl PS, Partilla JS, Seddik A, Zhang YW, Cao J, Holy M, Steinkellner T, Rudnick G, Baumann MH, Ecker GF, Newman AH, Sitte HH: Binding Mode Selection Determines the Action of Ecstasy Homologs at Monoamine Transporters. Mol Pharmacol. 2016 Jan; 2015 Oct 30. PMID: 26519222 Fenollar-Ferrer C, Stockner T, Schwarz TC, Pal A, Gotovina J, Hofmaier T, Jayaraman K, Adhikary S, Kudlacek O, Mehdipour AR, Tavoulari S, Rudnick G, Singh SK, Konrat R, Sitte HH, Forrest LR: Structure and regulatory interactions of the cytoplasmic terminal domains of serotonin transporter. Biochemistry. 2014 Aug 26; 2014 Aug 15. PMID: 25093911 Rudnick G, Krämer R, Blakely RD, Murphy DL, Verrey F: The SLC6 transporters: perspectives on structure, functions, regulation, and models for transporter dysfunction. Pflugers Arch. 2014 Jan; 2013 Dec 13. PMID: 24337881 Rudnick G: How do transporters couple solute movements? Mol Membr Biol. 2013 Nov. PMID: 24147977 Wong A, Zhang YW, Jeschke GR, Turk BE, Rudnick G: Cyclic GMP-dependent stimulation of serotonin transport does not involve direct transporter phosphorylation by cGMP-dependent protein kinase. J Biol Chem. 2012 Oct 19; 2012 Aug 31. PMID: 22942288 Bulling S, Schicker K, Zhang YW, Steinkellner T, Stockner T, Gruber CW, Boehm S, Freissmuth M, Rudnick G, Sitte HH, Sandtner W: The mechanistic basis for noncompetitive ibogaine inhibition of serotonin and dopamine transporters. J Biol Chem. 2012 May 25; 2012 Mar 26. PMID: 22451652 Schicker K, Uzelac Z, Gesmonde J, Bulling S, Stockner T, Freissmuth M, Boehm S, Rudnick G, Sitte HH, Sandtner W: Unifying concept of serotonin transporter-associated currents. J Biol Chem. 2012 Jan 2; 2011 Nov 9. PMID: 22072712 Rudnick G: Cytoplasmic permeation pathway of neurotransmitter transporters. Biochemistry. 2011 Sep 6; 2011 Aug 10. PMID: 21774491 Henry LK, Iwamoto H, Field JR, Kaufmann K, Dawson ES, Jacobs MT, Adams C, Felts B, Zdravkovic I, Armstrong V, Combs S, Solis E, Rudnick G, Noskov SY, DeFelice LJ, Meiler J, Blakely RD: A conserved asparagine residue in transmembrane segment 1 (TM1) of serotonin transporter dictates chloride-coupled neurotransmitter transport. J Biol Chem. 2011 Sep 2; 2011 Jul 5. PMID: 21730057