- Assistant Professor of Ophthalmology at CUMC
Environmental phenomena such as light, gravity, the earth’s magnetic pull, food, and our atmosphere are, for all practical purposes, inescapable. By providing the context for genetic variation, the environment has dictated our very evolution. That is, the human body’s unique response to the environment defines who we are as a species. Our objective is to elucidate and to improve the way humans interact with the environment on a molecular level. By doing so, we are begin to understand what happens during the course of disease and are discovering ways to improve and prolong life.
Rather than being constrained by any particular discipline, we approach scientific discovery by allowing the question at hand define our approach. This line of attack involves combining tools and knowledge from multiple scientific disciplines ranging from chemistry to biology in order to tackle fundamental problems of great interest. There are no rules here.
Solar radiation is an ubiquitous and essential component of our environment. Originating from nuclear fusion at the sun’s solar core, it travels to the sun’s surface and escapes into space as sunlight. This radiant energy is filtered through the atmosphere and the surrounding layer of ozone before reaching earth. One of our major goals is to discover ways in which light effects living organisms and biological processes, to control and manipulate these interactions to improve health. The eye, as our light-sensing organ, is a natural target for such investigations; however light also penetrates nearly all other organs. On a clear day the amount of light that penetrates your skull would allow you to comfortably read a book. Our research is built on basic questions. For example, humans are continuously exposed to increased levels of incandescent and/or fluorescent lighting, both of which have different spectral compositions than natural sunlight. What are the implications of this exposure, if any, for human health?
Oxygen & Energy
Oxygen is produced when water is split into its molecular components—oxygen and hydrogen—during photosynthesis. Hydrogen, as the lighter molecule, escapes our atmosphere, while oxygen is inhaled into our circulatory system where it makes its way from capillary blood to intracellular mitochondrial organelles, where it is burned for energy during the production of ATP. As declines in ATP are often associated with disease, we are also interested in how cells burn oxygen and store its energy as ATP.
Much like too much oxygen causes a candle to burn more quickly, too much oxygen becomes toxic and the proper storage and transport of oxygen within cells in critical. Oxidative damage is believed to be a root cause of aging and its associated diseases. We attempt to better understand the how cells to protect themselves from oxidative damage by studying how oxygen moves within cells.
We approach scientific discovery by allowing the question at hand define our approach. This line of attack involves combining tools and knowledge from multiple scientific disciplines ranging from chemistry to biology in order to tackle fundamental problems of great interest. There are no rules here.“
THE ROLE AND MECHANISMS OF LIPFUSCIN FORMATION IN MACULAR DEGENERATION (Federal Gov)
Feb 1 2011 - Jan 31 2017
PHASE 1 SAFETY AND PHARMACOKINETICS OF ALK001 IN PEOPLE OVER 60 (Federal Gov)
Sep 1 2012 - Aug 31 2013
DEUTERIUM ENRICHMENT OF VITAMIN A SLOWS LIPOFUSION (Private)
Apr 1 2010 - Mar 31 2013
THE DESIGN AND BIOLOGICAL TESTING OF RED VISION EYE DROPS (Federal Gov)
Oct 1 2007 - May 31 2011
Qu, J., Ma, L., Zhang, J., Jockusch, S., Washington, I. Dietary chlorophyll metabolites catalyze the photo reduction of plasma ubiquinone, Photochemistry and Photobiology, 2012, in press.
Qu, J., Ma, L., Washington, I. Retinal coenzyme Q in the bovine eye. Biofactors, 37(5):393-398, 2011.
Kaufman, Y., Ma, L., Washington, I. Deuterium enrichment of vitamin A at the C20 position slows the formation of detrimental vitamin a dimers in wild-type rodents. J. Biol. Chem., 286(10):7958-7965, 2011.
Ma, L., Kaufman, Y., Zhang, J., Washington, I. C20-D3-vitamin A slows lipofuscin accumulation and electrophysiological retinal degeneration in a mouse model of Stargardt’s disease. J. Biol. Chem., 286(10):7966-7974.
Qu, J., Kaufman, Y., Washington, I. Coenzyme Q10 in the Human Retina. Invest Ophthalmol Vis Sci., 50:1814-1818, 2009.
Washington, I., Zhou, J., Jockusch, S., Turro, N.J., Nakanishi,K., Sparrow, J.R. Chlorophyll Derivatives as Visual Pigments for Super Vision in the Red. Photochem. Photobiol. Sci., 6:775-779, 2007.
Lebedeva, I.V., Washington, I., Sarkar, D., Clark, J.A., Fine, R.L., Dent, P., Curiel, D.T., Turro, N.J., Fisher, P.B. Strategy for Reversing Resistance to a Single Anti-Cancer Agent in Human Prostate and Pancreatic Carcinomas. Proc. Natl. Acad. Sci. U. S. A.,104:3484-3489, 2007.
Isayama, T., Alexeev, D., Clint, M., Washington, I., Nakanishi, K., Turro, N.J. An Accessory Chromophore in Red Vision.Nature, 443:649, 2006.
Washington, I., Turro, N.J., Nakanishi, K. Superoxidation of Retinoic Acid. Photchemistry and Photobiology, 82:1394–1397, 2006.
Washington, I., Jockusch, S., Itagaki, Y., Turro, N.J., Nakanishi, K. Superoxidation of Bisretinoids. Angew. Chem. Int. Ed.,117: 7259-7262, 2005.
Poon, T., Sivaguru, J., Franz, R., Jockusch, S., Martinez, C., Washington, I., Adam, W., Inoue, Y., Turro, N.J. Temperature and Solvent Control of the Stereoselectivity in the Reactions of Singlet Oxygen with Oxazolidinone-Substituted Enecarbamates. J. Am. Chem. Soc.,126:10498-10499, 2004.
Washington, I., Brooks, C., Turro, N.J., Nakanishi, K. Porphyrins As Photosensitizers To Enhance Night Vision. J. Am. Chem. Soc., 126:9892-9893, 2004.
Prakesch, M., Gree, D., Gree, R., Carter, J., Washington, I., Houk, K.N. Stereoselectivity of Nitrile Oxide Cycloadditions to Chiral Allylic Fluorides: Experiment and Theory. Chem. Eur. J., 9:5664-5672, 2003.
Poon, T., Turro, N.J., Chapman, J., Lakshminarasimhan, P., Lei, X., Jockusch, S., Franz, R., Washington, I., Adam, W., Bosio, S.G. Stereochemical Features of the Physical and Chemical Interactions of Singlet Oxygen With Enecarbamates. Org. Lett., 5:4951-4953, 2003.
Washington, I., Houk, K.N., Armstrong, A. Strategies for the Design of Organic Aziridination Reagents and Catalysts: Transition Structures for Alkene Aziridinations by NH Transfer. J. Org. Chem., 68:6497-6501, 2003.
Washington, I., Houk, K.N. Epoxidations by Peracid Anions in Water: Ambiphilic Oxenoid Reactivity and Stereoselectivity. Org. Lett., 4:2661-2664,2002.
Washington, I., Houk, K.N. CH—O hydrogen bonding influences pie–facial stereoselective epoxidations. Angew. Chem. Int. Ed., 40:4485-4488, 2001.
Gree, D., Vallerie, L., Gree, R., Toupet, L., Washington, I., Pelicier, JP., Villacampa, M., Perez, J.M., Houk, K.N. Conformations of Allylic Fluorides and Stereoselectivities of Their Diels-Alder Cycloadditions. J. Org. Chem., 66:2374-2381, 2001.
Armstrong, A., Washington, I., Houk, K.N. Transition State Stereoelectronics in Alkene Epoxidations by Fluorinated Dioxiranes. J. Am. Chem. Soc., 122:6297-6298, 2000.
Washington, I, Houk, K.N. Transition States and Origins of Stereoselectivity of Epoxidations by Oxaziridinium Salts. J. Am. Chem. Soc., 122:2948-2949, 2000.