Cheryl M. Craft

Mary D. Allen Chair in Vision Research, Doheny Eye Institute
Professor, Ophthalmology and Cell and Neurobiology
Founding Chair, Department of Cell and Neurobiology (1994 - 2004)

Research Topics

1. Molecular Neurobiology
2. Gene regulation
3. Genetics of inherited blindness
4. Visual Arrestins
5. Photoreceptor G-protein coupled receptor
6. Cone phototransduction
7. Knockout Mice Models

Research Overview

The endowed Mary D. Allen (MDA) Laboratory for Vision Research, Doheny Eye Institute, was established in 1994 to focus on molecular and cell biology of inherited forms of blindness, including age related macular degeneration and retinitis pigmentosa. Dr. Cheryl M. Craft and her research team investigate retinal photoreceptors in health and disease and light/dark gene regulation. The NEI/NIH funded research program focuses on the mechanisms involved in cone pigment G-protein signal transduction pathways:

(1) With the identification of a superfamily of arrestin proteins (Craft, Whitmore, and Wiechmann, 1994; Craft and Whitmore, 1995), visual arrestins are critical players in cone pigment photoreceptor signaling. Arrestin1 mutations are responsible for a form of retinitis pigmentosa, known as Oguchi?s Disease. Our discovering of a second visual arrestin in cones now focuses on current research with mouse and Xenopus models to analyze the gene structure/function. In parallel to basic transcriptional regulation experiments, series of genetic knockouts to examine the electrophysiological, biochemical and morphological phenotype of the cone transduction machinery without this cone opsin regulator are ongoing (Zhu et al., 2003, Danielle et al., 2005).

(2) Also in Dr. Craft's group has worked with retinal tumor cell lines to study the cone photoreceptor enriched signal transduction cascade phenotype and the developmental triggers involved in differentiation (Li et al., 2003, Zhang et al., 2004). Using Affymetrix Gene Chip technology, we determined the genes that regulate and modulate differentiation that may be essential for the long-term survival of this retinal cell line and potentially embryonic stem cells. Ongoing work is examining if these differentiated retinal cells will be useful in a transplantation models to retain the cytoarchitecture of the degenerating retina. Additional structure/function studies by a 2005 neuroscience doctoral graduate, Shiyi (Echo) Wei Pickrell, Ph.D., deciphered the molecular ?zipcodes? for expression of retinal genes involved in the signal transduction pathway utilizing the Xenopus laevis Green Fluorescent Protein reporting system, molecular transfection of mutated and altered promoter regions, Cre-targeted cone mice (Pickrell et al., 2003, Akimoto et al., 2004).

(3) Dr. Craft developed a retinal yeast two-hybrid library screening technology and discovered significant protein partners for phosducin isoforms: SUG1 is involved in proteosomal degradation and CRX is a cone rod homeobox transcription factor (Mol. Cell Biol., 2000). Phosducin, normally found in the cytoplasm, regulates Gbg binding proteins; however, phosducin also can enter the nucleus and inhibit the transcriptional activity of CRX, the major developmental regulator that determines the cone and rod photoreceptor lineage. Current work identified novel synaptic interacting partners, including CPE, that involve the survival of photoreceptor function (Zhu et al., 2005).