Ernest Marshall Wright, Ph.D., D.Sc.

Work Address:
10833 Le Conte Ave.
CHS 53-317
Los Angeles, CA 90095

Professor, Physiology
Member, Brain Research Institute, CTSI, JCCC Cancer Molecular Imaging, JCCC Genitourinary Oncology Program Area, Molecular, Cellular & Integrative Physiology GPB Home Area, Workforce Development
Research Interests
The major goal of this program is to understand how ion gradients drive the accumulation of sugars, amino acids, dipeptides, osmolytes and neurotransmitters in cells. Our approach is to express cloned Na and H driven transporters in heterologous expressions systems and to monitor transport using biophysical techniques. Structure/function relations are explored using mutants and chimeras, and regulation is studied by activating protein kinases. In addition, we are working on a genetic disease called glucose-galactose malabsorption that is caused by defects in the intestinal Na/glucose cotransporter. Patients with the disease are screened for mutations and then we seek to unravel why the mutation causes defective sugar absorption. So far, we have identified missense, nonsense and splice-site mutations, and in the case of the missense mutations it appears that trafficking of the protein to the plasma membrane is impaired. Therapies are being developed to cure the disease.

Ernest Wright, professor of physiology and Mellinkoff Professor in Medicine at the David Geffen School of Medicine at UCLA, has been named a 2005 Fellow to the Royal Society, an honor considered one of the highest accolades a scientist can achieve next to the Nobel Prize. Born in Belfast, Ireland, Wright joined the faculty of the medical school in 1967, and was tapped to chair the physiology department in 1987. His research focuses on the structure, function and genetics of transport proteins, which act as gatekeepers for the body by carrying essential molecules in and out of cells. In 2003, his research team identified a new protein that senses changes in glucose, the blood sugar that fuels body function. The UCLA discovery could lead to the development of new drugs to control diabetes and obesity. I n his 38-year tenure at UCLA, Wright has mentored more than 40 postdoctoral fellows and graduate students. During his career, he received the Senator Jacob K. Javits Neuroscience Investigator Award from the National Institutes of Health from 1985 to 1992, and was named the Walter B. Cannon Distinguished Lecturer by the American Physiological Society in 1989, the G.W. Harris Lecturer by the British Physiological Society in 1990 and a Fellow of the Biophysical Society in 2005. He has served on the editorial boards for several physiology journals, consults for the National Institutes of Health, and is a scientific advisor to the Eli and Edythe L. Broad Medical Foundation in Los Angeles. Wright earned his doctorate degrees in physiology from London University and Sheffield University in England, and conducted his research fellowship at Harvard University in Boston.


A selected list of publications:

Wright Ernest M   Glucose transport families SLC5 and SLC50 Molecular aspects of medicine, ; 34(2-3): 183-96.
Yu Amy S, Hirayama Bruce A, Timbol Gerald, Liu Jie, Diez-Sampedro Ana, Kepe Vladimir, Satyamurthy Nagichettiar, Huang Sung-Cheng, Wright Ernest M, Barrio Jorge R   Regional distribution of SGLT activity in rat brain in vivo American journal of physiology. Cell physiology, 2013; 304(3): C240-7.
Sala-Rabanal Monica, Hirayama Bruce A, Loo Donald D F, Chaptal Vincent, Abramson Jeff, Wright Ernest M   Bridging the gap between structure and kinetics of human SGLT1 American journal of physiology. Cell physiology, 2012; 302(9): C1293-305.
Ghezzi Chiara, Wright Ernest M   Regulation of the human Na+ dependent glucose cotransporter hSGLT2 American journal of physiology. Cell physiology, 2012; .
Hummel Charles S, Lu Chuan, Liu Jie, Ghezzi Chiari, Hirayama Bruce A, Loo Donald D F, Kepe Vladimir, Barrio Jorge R, Wright Ernest M   Structural selectivity of human SGLT inhibitors American journal of physiology. Cell physiology, 2012; 302(2): C373-82.
Jiang Xuan, Loo Donald D F, Hirayama Bruce A, Wright Ernest M   The importance of being aromatic: π interactions in sodium symporters Biochemistry, 2012; 51(47): 9480-7.
Wright Ernest M, Loo Donald D F, Hirayama Bruce A   Biology of human sodium glucose transporters Physiological reviews, 2011; 91(2): 733-94.
Sala-Rabanal, M, Hirayama, BA, Loo, DDF, Chaptal, V, Abramson, J, and Wright, EM.   Bridging the Gap between Structure and Kinetics of Human SGLT1 Am J Physiol Cell Physiol; , 2011; 2011 Dec 7. [Epub ahead of print]: .
Zampighi Guido A, Schietroma Cataldo, Zampighi Lorenzo M, Woodruff Michael, Wright Ernest M, Brecha Nicholas C   Conical tomography of a ribbon synapse: structural evidence for vesicle fusion PloS one, 2011; 6(3): e16944.
Hummel Charles S, Lu Chuan, Loo Donald D F, Hirayama Bruce A, Voss Andrew A, Wright Ernest M   Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and SGLT2 American journal of physiology. Cell physiology, 2011; 300(1): C14-21.
Hummel, CS, Lu, C, Liu, J, Gheezi, C, Hirayama, BA, Loo, DDF, Kepe, V, Barrio, JR, Wright, EM.   Structural selectivity of human SGLT inhibitors. Am J Physiol Cell Physiol, 2011; 302(2): C373 - C382.
Yu Amy S, Hirayama Bruce A, Timbol Gerald, Liu Jie, Basarah Ernest, Kepe Vladimir, Satyamurthy Nagichettiar, Huang Sung-Cheng, Wright Ernest M, Barrio Jorge R   Functional expression of SGLTs in rat brain American journal of physiology. Cell physiology, 2010; 299(6): C1277-84.
Watanabe Akira, Choe Seungho, Chaptal Vincent, Rosenberg John M, Wright Ernest M, Grabe Michael, Abramson Jeff   The mechanism of sodium and substrate release from the binding pocket of vSGLT Nature, 2010; 468(7326): 988-91.
Choe Seungho, Rosenberg John M, Abramson Jeff, Wright Ernest M, Grabe Michael   Water permeation through the sodium-dependent galactose cotransporter vSGLT Biophysical journal, 2010; 99(7): L56-8.
Bakris George L, Fonseca Vivian A, Sharma Kumar, Wright Ernest M   Renal sodium-glucose transport: role in diabetes mellitus and potential clinical implications Kidney international, 2009; 75(12): 1272-7.
Abramson Jeff, Wright Ernest M   Structure and function of Na(+)-symporters with inverted repeats Current opinion in structural biology, 2009; 19(4): 425-32.
Zampighi Guido A, Fain Nick, Zampighi Lorenzo M, Cantele Francesca, Lanzavecchia Salvatore, Wright Ernest M   Conical electron tomography of a chemical synapse: polyhedral cages dock vesicles to the active zone The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008; 28(16): 4151-60.
Loo Donald D F, Hirayama Bruce A, Sala-Rabanal Monica, Wright Ernest M   How drugs interact with transporters: SGLT1 as a model The Journal of membrane biology, 2008; 223(2): 87-106.
Sala-Rabanal Monica, Loo Donald D F, Hirayama Bruce A, Wright Ernest M   Molecular mechanism of dipeptide and drug transport by the human renal H+/oligopeptide cotransporter hPEPT2 American journal of physiology. Renal physiology, 2008; 294(6): F1422-32.
Faham Salem, Watanabe Akira, Besserer Gabriel Mercado, Cascio Duilio, Specht Alexandre, Hirayama Bruce A, Wright Ernest M, Abramson Jeff   The crystal structure of a sodium galactose transporter reveals mechanistic insights into Na+/sugar symport Science (New York, N.Y.), 2008; 321(5890): 810-4.
Voss Andrew A, Díez-Sampedro Ana, Hirayama Bruce A, Loo Donald D F, Wright Ernest M   Imino sugars are potent agonists of the human glucose sensor SGLT3 Molecular pharmacology, 2007; 71(2): 628-34.
Hirayama Bruce A, Loo Donald D F, Díez-Sampedro Ana, Leung Daisy W, Meinild Anne-Kristine, Lai-Bing Mary, Turk Eric, Wright Ernest M   Sodium-dependent reorganization of the sugar-binding site of SGLT1 Biochemistry, 2007; 46(46): 13391-406.
Turk Eric, Gasymov Oktay K, Lanza Seren, Horwitz Joseph, Wright Ernest M   A reinvestigation of the secondary structure of functionally active vSGLT, the vibrio sodium/galactose cotransporter Biochemistry, 2006; 45(5): 1470-9.
Loo Donald D F, Hirayama Bruce A, Karakossian Movses H, Meinild Anne-Kristine, Wright Ernest M   Conformational dynamics of hSGLT1 during Na+/glucose cotransport The Journal of general physiology, 2006; 128(6): 701-20.
Donal D.F. Loo, Bruce A. Hirayama, Movses H. Karakossian, Anne-Kristine Meinild and Ernest M. Wright   Conformational dynamics ofr hSGLT1 during Na/glucose cotransport, J. General Physiology, 2006; 128(6): 701-720.
Sala-Rabanal Monica, Loo Donald D F, Hirayama Bruce A, Turk Eric, Wright Ernest M   Molecular interactions between dipeptides, drugs and the human intestinal H+ -oligopeptide cotransporter hPEPT1 The Journal of physiology, 2006; 574(Pt 1): 149-66.
Loo Donald D F, Hirayama Bruce A, Cha Albert, Bezanilla Francisco, Wright Ernest M   Perturbation analysis of the voltage-sensitive conformational changes of the Na+/glucose cotransporter The Journal of general physiology, 2005; 125(1): 13-36.
Díez-Sampedro Ana, Loo Donald D F, Wright Ernest M, Zampighi Guido A, Hirayama Bruce A   Coupled sodium/glucose cotransport by SGLT1 requires a negative charge at position 454 Biochemistry, 2004; 43(41): 13175-84.
Veenstra Marloes, Lanza Seren, Hirayama Bruce A, Turk Eric, Wright Ernest M   Local conformational changes in the Vibrio Na+/galactose cotransporter Biochemistry, 2004; 43(12): 3620-7.
Wright Ernest M, Loo Donald D F, Hirayama Bruce A, Turk Eric   Surprising versatility of Na+-glucose cotransporters: SLC5 Physiology (Bethesda, Md.), 2004; 19(1): 370-6.
Wright Ernest M, Turk Eric   The sodium/glucose cotransport family SLC5 Pflügers Archiv : European journal of physiology, 2004; 447(5): 510-8.
Diez-Sampedro Ana, Hirayama Bruce A, Osswald Christina, Gorboulev Valentin, Baumgarten Katharina, Volk Christopher, Wright Ernest M, Koepsell Hermann   A glucose sensor hiding in a family of transporters Proceedings of the National Academy of Sciences of the United States of America, 2003; 100(20): 11753-8.
Sarkar Hemanta K, Wright Ernest M, Boorer Kathryn J, Loo Donald D F   Electrophysiological properties of the mouse Na+/Cl(-)-dependent taurine transporter (mTauT-1): steady-state kinetics: stoichiometry of taurine transport Advances in experimental medicine and biology, 2003; 526(5): 197-204.
Quick Matthias, Tomasevic Jelena, Wright Ernest M   Functional asymmetry of the human Na+/glucose transporter (hSGLT1) in bacterial membrane vesicles Biochemistry, 2003; 42(30): 9147-52.
Wright Ernest M, Martín Martín G, Turk Eric   Intestinal absorption in health and disease--sugars Best practice & research. Clinical gastroenterology, 2003; 17(6): 943-56.
Zampighi Guido A, Kreman Michael, Lanzavecchia Salvatore, Turk Eric, Eskandari Sepehr, Zampighi Lorenzo, Wright Ernest M   Structure of functional single AQP0 channels in phospholipid membranes Journal of molecular biology, 2003; 325(1): 201-10.
Quick Matthias, Wright Ernest M   Employing Escherichia coli to functionally express, purify, and characterize a human transporter Proceedings of the National Academy of Sciences of the United States of America, 2002; 99(13): 8597-601.
Meinild Anne-Kristine, Hirayama Bruce A, Wright Ernest M, Loo Donald D F   Fluorescence studies of ligand-induced conformational changes of the Na(+)/glucose cotransporter Biochemistry, 2002; 41(4): 1250-8.
le Coutre Johannes, Turk Eric, Kaback H Ronald, Wright Ernest M   Ligand-induced differences in secondary structure of the Vibrio parahaemolyticus Na+/galactose cotransporter Biochemistry, 2002; 41(25): 8082-6.
Fischer Wolf-N, Loo Donald D F, Koch Wolfgang, Ludewig Uwe, Boorer Kathryn J, Tegeder Mechthild, Rentsch Doris, Wright Ernest M, Frommer Wolf B   Low and high affinity amino acid H+-cotransporters for cellular import of neutral and charged amino acids The Plant journal : for cell and molecular biology, 2002; 29(6): 717-31.
Wright Ernest M, Turk Eric, Martin Martin G   Molecular basis for glucose-galactose malabsorption Cell biochemistry and biophysics, 2002; 36(2-3): 115-21.
Loo Donald D F, Wright Ernest M, Zeuthen Thomas   Water pumps The Journal of physiology, 2002; 542(Pt 1): 53-60.
Loo Donald D.F., Wright Ernest M., Meinild Anne-Kristine, Klaerke Dan A., Zeuthen Thomas   Commentary on "Epithelial Fluid Transport--A Century of Investigation" News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society, 1999; 14: 98-100.
Eskandari S, Snyder PM, Kreman M, Zampighi GA, Welsh MJ, Wright EM   Number of subunits comprising the epithelial sodium channel The Journal of biological chemistry. , 1999; 274(38): 27281-6.
Loo DDF.,Hirayama BA., Gallarado EM, Lam JT.,Turk E., Wright EM.   Conformational changes copule Na and glucose transport, PNAS, 1998; 95: 7789-7794.
Eskandari S, Wright EM, Kreman M, Starace DM, Zampighi GA   Structural analysis of cloned plasma membrane proteins by freeze-fracture electron microscopy Proceedings of the National Academy of Sciences of the United States of America. , 1998; 95(19): 11235-40.
Meinild A, Klaerke DA, Loo DD, Wright EM, Zeuthen T   The human Na+-glucose cotransporter is a molecular water pump The Journal of physiology. , 1998; 508 ( Pt 1): 15-21.
Turk E and Wright EM   Membrane Topological Motifs in the SGLT Cotransporter Family, J. Membrane Biology, 1997; 159: 1-20.
Eskandari S, Loo DDF, Dai G, Levy R, Wright EM and Carracso N   Thyroid Na+/I-Symporter: Mechanisms, Stoichiometry, and Specificity, J. Biol. Chem, 1997; 272: 27230-27238.
Mart-n MG, Turk E, Lostao MP, Kerner C, Wright EM   Defects in Na+/glucose cotransporter (SGLT1) trafficking and function cause glucose-galactose malabsorption Nature genetics. , 1996; 12(2): 216-20.