Ching-Kang Jason Chen, Ph.D.Associate Professor of Biochemistry & Molecular Biology
PO Box 980614
Richmond, VA 23298-0614
Telephone: (804) 828-9762
- B.S., 1985, Tunghai University, Taiwan
- M.S., 1987, National Taiwan University, Taiwan
- Ph.D., 1995, University of Washington
1996-2000, California Institute of Technology
We use biochemical, electrophysiological, and genetic tools to study the biology of vertebrate retinal photoreceptors. These post-mitotic and highly differentiated cells transduce visible light into electrical signals. Two types of morphologically distinctive photoreceptors are found in the retina. Rod photoreceptors, responsible for dim light vision due to their higher sensitivity, transduce light relatively slower. Cone photoreceptors, responsible for daytime vision and color vision, are less sensitive but transduce light much faster than rods. The biochemical reactions linking photon absorption to the generation of neural signals is a canonical G-protein signal transduction pathway called phototransduction, in which rod and cone photoreceptors use cGMP as a second messenger. Certain proteins are used by both photoreceptors but each type of cells expresses distinct sets of proteins for the task. Our long-term goal is to recount the molecular basis of the differences in sensitivity and response kinetics in rod and cone phototransduction. Our short-term aims are to determine the rate-limiting steps in the recovery of rod phototransduction pathway and to delineate the function of GRK7, a seventh member of the G-protein coupled receptor kinase family found in cone photoreceptors of several mammalian species including human.
Individuals whose photoreceptors sustain genetic or environmental insults suffer from photoreceptor degeneration, a clinical condition with very limited treatment options. Unlike other inherited degenerative diseases of the central nervous system, in which mutations occur with common structural features (as in the trinucleotide repeat expansion disease) or in groups of genes with related functions (as in Alzheimer’s disease), the degeneration of photoreceptors can be triggered by mutations in a wide variety of genes. As of May of 2005, 158 genetic loci are linked to retinal diseases and among them 110 genes are identified. A good portion of these genes are expressed in a photoreceptor-specific fashion while several others are ubiquitously expressed. Many animal models mimicking the phenotypic expression of mutations in human are identified or made by targeted genetics. None of the pathologic mechanisms in these models is known, but it is widely accepted that programmed cell death is centrally involved. We hypothesize that these multiple individual forms of photoreceptor degeneration converge down to just a few preapoptotic pathways. We will test the hypothesis by conditional targeted genetic approaches in mice. Our short-term aims are to determine the roles of caspase activation as well as the involvement of apoptosis-inducing factor (AIF) during photoreceptor degeneration. The long-term goal is to identify novel therapeutic and pharmaceutical modalities to diagnose/prevent/treat the degeneration of retinal photoreceptors.