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Krzysztof Palczewski, PhDE.K. Bishop Professor, OphthalmologyAdjunct Professor, PharmacologyJoint Professor, ChemistryLaboratory Website· Office Telephone: (206) 543-9074· Fax Direct to Office: (206) 221-6784· Laboratory (RR835): (206) 543-3084· Laboratory (RR837): (206) 543-4899· Laboratory (RR843): (206) 543-6399· Laboratory (RR847/849): 543-7489palczews@u.washington.eduAdministrative Coordinator: (206) 221-5295 |
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LABORATORY PERSONNEL: |
Andrei M. Alekseev, PhD, Senior FellowYu-Guang He, MD, Vitreoretinal FellowYoshikazu Imanishi, PhD Senior FellowGeeng-Fu Jang, PhD, Senior FellowVladimir A. Kuksa, PhD, Senior FellowAkiko Maeda, MD, PhD, Senior FellowTadao Maeda, MD, PhD, Senior FellowJosh McBee, MS, Predoctoral Research AssociateIzabela Sokol, PhD, Senior FellowJ. Preston Van Hooser, BS, Research Technologist |
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EDUCATION | |||
| 1980 | MS, Organic Chemistry, University of Wroclaw, Poland | ||
| 1986 | PhD, Biochemistry, Technical University of Wroclaw, Poland | ||
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POSTGRADUATE TRAINING | |||
| 1980-1986 | Junior/Senior Research Fellow, Department of Biochemistry, Technical University of Wroclaw, Poland | ||
| 1983 | (Feb-July) Research Assistant, Southern Illinois University, Carbondale, Ill. | ||
| 1986-1988 | Postdoctoral Fellow, University of Florida, Gainesville | ||
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FACULTY POSITIONS HELD | |||
| 1988-1989 | Assistant Research Scientist, Department of Ophthalmology, University of Florida, Gainesville | ||
| 1990-1992 | Assistant Scientist II, Robert S. Dow Neurological Sciences Institute and Department of Ophthalmology, Good Samaritan Hospital and Medical Center, Portland, Ore. | ||
| 1990-1992 | Assistant Professor of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland | ||
| 1990-1992 | Research Assistant Professor of Ophthalmology, Oregon Health Sciences University, Portland | ||
| 1990-date | Adjunct Research Scientist, Department of Ophthalmology, University of Florida, Gainesville | ||
| 1991-1992 | Associate Scientist I, Robert S. Dow Neurological Sciences Institute, Good Samaritan Hospital and Medical Center, Portland, Ore. | ||
| 1992-1994 | Assistant Professor, Department of Ophthalmology; Department of Pharmacology (Adjunct); University of Washington, Seattle | ||
| 1992-date | Affiliate, Center on Human Development and Disability (CHDD), University of Washington, Seattle | ||
| 1994-1997 | Associate Professor, Department of Ophthalmology; Pharmacology (Adjunct), University of Washington, Seattle | ||
| 1997-1999 | Professor, Department of Ophthalmology, University of Washington, Seattle | ||
| 1997-date | Professor (Adjunct), Pharmacology, University of Washington, Seattle | ||
| 1998-date | Professor (Joint), Department of Chemistry, University of Washington, Seattle | ||
| 1999-date | E.K. Bishop Professor, Department of Ophthalmology, University of Washington, Seattle | ||
| 1999-date | Research Affiliate, Regional Primate Research Center, University of Washington, Seattle | ||
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HONORS | |||
| Polish Academy of Science (1978, '85) | |||
| Polish Ministry of Education (1986) | |||
| NIH Study Section, Ad hoc Participant (1990, '95, '96, '99) | |||
| Jules and Doris Stein Research to Prevent Blindness Professor (1992-99) | |||
| Cogan Award, Association for Research in Vision and Ophthalmology (1996) | |||
| Alcon Research Institute Award (2001) | |||
EDITORIAL BOARD MEMBERSHIP | |||
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Investigative Ophthalmology & Visual Science Acta Biochimica Polonica (Polish Biochemical Society, Polish Academy of Sciences) | |||
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RESEARCH INTERESTS | |||
Vision displays an amazing dynamic range, allowing detection of visual stimuli over a 106-fold variation in illumination intensities. Light captured by rod and cone cells of the retina triggers phototransduction.  This cascade of chemical reactions is similar in both types of cells and is responsible for generating a neuronal signal. Phototransduction proceeds through a series of highly specific interactions between proteins that are critical for normal photoreceptor function; however, rod and cone cells exhibit distinct response kinetics and sensitivities to different intensities and wavelengths of light. Another difference between these cells is their degree of desensitization to background light. As a more thorough understanding of phototransduction emerges at the chemical level and new photoreceptor proteins are discovered, so, too, does our understanding of human retinopathies that result from mutations of proteins involved. Restoration of the inactive receptor conformation in vertebrates requires the formation of 11-cis-retinal from an all-trans- precursor via a pathway of enzymatic reactions called the visual cycle. The first step of the visual cycle, the reduction of all-trans-retinal to all-trans-retinol, takes place in photoreceptor outer segments, whereas the other reactions, including isomerization, occur within the retinal pigment epithelium. Purification of enzymes from the visual cycle eluded enzymologists for years. Consequently, there is no molecular information about the enzymes, and their properties and regulation have not been established. A chemical and molecular understanding of the regeneration process may have important implications for understanding common human retinopathies such as age-related macular degeneration and retinitis pigmentosa.The long-term objectives of our laboratory are to understand the molecular events initiated by light in photoreceptor cells. Specifically, we are examining the biochemical and functional aspects of phototransduction that are critical for the restoration of the dark condition of the cell. These studies focus on new biochemical information about the steps in phototransduction that are, as yet, poorly understood but critical for normal function of photoreceptors. Rigorous chemical analysis of events during phototransduction and regeneration, analysis of the post-translational modification proteins involved, and identification of new chemical and protein components and intermediates are the immediate goals of our laboratory. Phototransduction is an archetype of signal transduction pathways initiated by activation of the G protein-coupled receptors, including the adrenergic, muscarinic, opioid, and other receptors. Our overall understanding of this general mode of signal transduction is being advanced by novel findings in phototransduction. | |||
RECENT SIGNIFICANT PUBLICATIONS | |||
PALCZEWSKI K, Buczylko J, Kaplan MW, Polans AS, Crabb J: Mechanism of rhodopsin kinase activation. J Biol Chem 1991; 266: 12949-55. Hofmann KP, Pulvermüller A, Buczylko J, Van Hooser P, PALCZEWSKI K: The role of arrestin in regeneration pathway of rhodopsin. J Biol Chem 1992; 267: 15701-6. PALCZEWSKI K, Subbaraya I, Gorczyca WA, Helekar BS, Ruiz CC, Ohguro H, Huang J, Zhao X, Crabb JW, Johnson RS, Walsh KA, Gray-Keller MP, Detwiler PB, Baehr W: Molecular cloning and characterization of retinal photoreceptor guanylyl cyclase activating protein. Neuron 1994; 13: 395-404. Ohguro H, Van Hooser JP, Milam AH, PALCZEWSKI K: Rhodopsin phosphorylation and dephosphorylation in vivo. J Biol Chem 1995; 270: 14259-62. Sokal I, Li N, Surgucheva I, Warren MJ, Payne AM, Bhattacharya SS, Baehr W, PALCZEWSKI K: GCAP1 (Y99C) mutant is constitutively active in autosomal dominant cone dystrophy. Molecular Cell 1998; 2(1): 129-33. Otto-Bruc AE, Fariss RN, Van Hooser JP, PALCZEWSKI K: Phosphorylation of photolyzed rhodopsin is calcium-insensitive in retina permeabilized by alpha-toxin. Proc Natl Acad Sci USA 1998; 95: 15014-19. Haeseleer F, Sokal I, Verlinde CLMJ, Erdjument-Bromage H, Tempst P, Pronin AN, Benovic JL, Fariss RN, PALCZEWSKI K: Five members of a novel Ca2+-binding protein (CaBP) subfamily with similarity to calmodulin. J Biol Chem 2000; 275: 1247-60. PALCZEWSKI K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M: Crystal structure of rhodopsin: a G-protein-coupled receptor. Science 2000; 289: 739-45. Teller DC, Okada T, Behnke CA, PALCZEWSKI K, Stenkamp RE: Advances in determination of a high-resolution three-dimensional structure of rhodopsin, a model of G-protein-coupled receptors (GCPRs). Biochemistry 2001; 40: 7761-72. Polans A, Baehr W, PALCZEWSKI K: Turned on by Ca2+! The physiology and pathology of Ca2+-binding proteins in the retina. Trends in Neurosci 1996; 19: 547-54. PALCZEWSKI K, Polans AS, Baehr W, Ames JB: Ca2+-binding proteins in the retina: structure, function, and the etiology of human visual diseases. BioEssays 2000; 22: 337-50. Okada T, Ernst OP, PALCZEWSKI K, Hofmann KP: Activation of rhodopsin: New insights from structural and biochemical studies. Trends Biochem Sci 2001; 26: 318-24. McBee JK, PALCZEWSKI K, Baehr W, Pepperberg DR: "Confronting Complexity: the Interlink of Phototransduction and Retinoid Metabolism in the Vertebrate retina," In: Osborne NN & Chader GJ (eds.): Progress in Retinal Research, vol. 20. Copyright 2001 Elsevier Science Ltd.; pp. 469-529. | |||
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