UW Department of Ophthalmology: JOHN C SAARI, PhD

John C. Saari, PhD

Professor of Ophthalmology

and Biochemistry (Joint)

Office phone: (206) 543-5633

FAX: (206) 543-4414

jsaari@u.washington.edu

Saari Lab: (206) 543-5792

Laboratory Personnel:

Greg Garwin, Research Technologist

Jing Huang, MD, Research Technologist

Maria Nawrot, PhD, Research Technologist


	EDUCATION
	1961	BS, Chemistry, University of Oklahoma, Norman
	1963	MS, Biochemistry, University of Minnesota, Minneapolis/St. Paul
	1970	PhD, Biochemistry, University of Washington, Seattle
	POSTGRADUATE TRAINING
	1971-1972	Postdoctoral Fellow, Service de Biochimie Cellulaire, Institut Pasteur, Paris XV, France
	1973-1974	Research Associate, The Rockefeller University, New York, N.Y.
	FACULTY POSITIONS HELD
	1975-1979	Assistant Professor, Department of Ophthalmology; Adjunct, Biochemistry; University of Washington, Seattle
	1979-1984	Associate Professor, Department of Ophthalmology; Adjunct, Biochemistry; University of Washington, Seattle
	1984-1985	Associate Professor, Department of Ophthalmology; Joint, Biochemistry; University of Washington, Seattle
	1985-date	Professor, Department of Ophthalmology; Joint, Biochemistry; University of Washington, Seattle
	AWARDS
	Senior Scientific Investigator, Research to Prevent Blindness, Inc. (1993-date) Friedenwald Award (1999 Meeting of the Association for Research in Vision and Ophthalmology)
	SELECTED PROFESSIONAL RESPONSIBILITIES
	Association for Research in Vision and Ophthalmology (ARVO) Program Committee, Biochemistry Section, 1986-88 Federation of American Societies for Experimental Biology (FASEB) Retinoid Conference Co-Chair, June 1996 Retinoid Conference Chair, June 1998 National Eye Institute, National Institutes of Health (NEI/NIH) Visual Sciences C Study Section Member, 1990-93 (Full Term) EDITORIAL BOARD MEMBERSHIP Experimental Eye Research (1985-90) Investigative Ophthalmology & Visual Science (1992-97) Journal of Biological Chemistry (1992-97) Molecular Vision (1995-date)
	RESEARCH INTERESTS
	Light isomerizes 11-cis-retinal, the chromophore of vertebrate visual pigments; activates rhodopsin; and initiates the phototransduction cascade of reactions. The product of photoisomerization, all-trans-retinal, enters into a reaction pathway that regenerates the 11-cis-configuration and the native visual pigment. At any given physiologic level of illumination, a steady state is established in which the rate of visual pigment photoisomerization is equal to, and opposed by, the rate of regeneration. The log-sensitivity of the retina is inversely proportional to the steady-state level of bleached visual pigment. Thus, phototransduction, regeneration, and visual sensitivity are tightly linked in a process that has been called the visual pigment. Work in my laboratory is directed towards obtaining a molecular understanding of visual cycle reactions and retinoid transport processes. Recent studies employing HPLC analysis of visual cycle intermediates demonstrated that all-trans-retinal is the only retinoid that accumulates during steady-state cycling of the mouse visual system and that the rate of regeneration is very similar to the rate of decay of all-trans-retinal. This implies that all reactions and processes of the visual cycle that follow reduction of all-trans-retinal are rapid and that all-trans-retinol dehydrogenase (RDH) catalyzes a slow step. Thus, reduction of all-trans-retinal by RDH plays a pivotal role in the visual cycle because its rate determines entry of all-trans-retinal into the regeneration pathway, and it is the ultimate quenching reaction of phototransduction. Analysis of the retinoid composition and rhodopsin kinetics of transgenic mice is providing novel information about the roles of retinoid-binding proteins and phototransduction components in the visual cycle. Studies of the enzymology and molecular biology of visual cycle enzymes and proteins (for instances, all-trans-retinol dehydrogenase of photoreceptor cells and cellular retinaldehyde-binding protein of retinal pigment epithelium) will provide important tools for continued studies of the role of these components in inherited retinal diseases.
	RECENT PUBLICATIONS
	Stecher H, Gelb MH, SAARI JC, Palczewski K: Preferential release of 11-cis-retinol from retinal pigment epithelial cells in the presence of cellular retinaldehyde-binidng protein (CRALB). J Biol Chem 1999; 247: 8577-85 SAARI JC: The biochemistry of visual pigment regeneration. Friedenwald Lecture. Invest Ophthalmol Vis Sci 2000; 41: 337-48. Garwin GG, SAARI JC: High-performance liquid chromatography analysis of visual cycle retinoids. Meth Enzymol 2000; 316: 313-24. SAARI JC, Garwin GG, Haeseleer F, Jang G-F, Palczewski K: Phase partition and HPLC assays of retinoid dehydrogenase. Meth Enzymol 2000; 316: 359-71. Taylor MR, Van Epps HA, Kennedy MJ, SAARI JC, Hurley JB, Brockerhoff SE: Biochemical methods to analyze phototransduction and the visual cycle in zebrafish larvae. Meth Enzymol 2000; 316: 536-77. Van Hooser JP, Garwin GG, SAARI JC: Analysis of the visual cycle in transgenic mice. Meth Enzymol 2000; 316: 565-75. Sires BS, SAARI JC, Garwin GG, Hurst JS, van Kuijk FJGM: The color difference in orbital fat. Arch Ophthalmol 2001; 119: 868-71. SAARI JC, Nawrot M, Kennedy BN, Garwin GG, Hurley JB, Huang J, Possin DE, Crabb JW: Visual cycle impairment in cellular retinaldehyde-binding protein (CRALBP) knockout mice results in delayed dark adaptation. Neuron 2001; 29: 739-48. Kennedy MJ, Lee KA, Niemi GA, Craven KB, Garwin GG, SAARI JC, Hurley JB: Multiple phosphorylation of rhodopsin and the in vivo chemistry underlying rod photoreceptor dark adaptation. Neuron 2001; 31: 87-101. SAARI JC: The sights along route 65. Nature Genetics 2001; 29: 8-9. SAARI JC, Nawrot M, Garwin GG, Kennedy MJ, Hurley JB, Ghyselinck NB, Chambon P: Analysis of the visual cycle in cellular retinol-binding protein type I (CRBPI) null mice. Invest Ophthalmol Vis Sci (In Press).

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