Constance L. Cepko, Ph.D.

Professor of Genetics

Harvard Medical School
New Research Building, Room 360
77 Avenue Louis Pasteur
Boston, MA 02115
Tel: (617) 432-7618
Fax: (617) 432-7595
Email: cepko@genetics.med.harvard.edu
Predocs: 3 Postdocs: 10 Completed PhD's: 17

We are interested in the mechanisms that direct development of the central nervous system (CNS) of vertebrates. We are focusing our studies on the vertebrate retina, a relatively simple and well-characterized area of the CNS. We have used genomics approaches to examine gene expression over time during murine retinal development. We have further investigated the cellular specificity of expression patterns by performing in situ hybridization for >1500 genes with dynamic temporal patterns, and by performing gene profiling on single retinal cells. These studies led to the identification of many excellent candidate genes suspected to be important in development, along with many newly-characterized genes that are enriched or specific in their expression to photoreceptor cells. As many disease genes that affect vision have been found to exhibit photoreceptor-specific or enriched expression, these genes are an excellent set of candidate genes for these diseases. We are also characterizing gene expression changes that accompany photoreceptor death in murine models of the human diseases, retinitis pigmentosa, cone-rod dystrophy, and macular degeneration. Finally, genes that control the initial formation and pattern of the retina are being characterized in chicks as well as mice. To understand the function of genes identified in genomics and other screens, we are using retroviral transduction or electroporation in vivo or in vitro to misexpress genes or reduce gene function using RNAi. In vitro culture systems that mimic retinal development have been developed and are being used to investigate the role of the environment.

References:

• Corbo, J., Cepko, C. A hybrid photoreceptor expressing both rod and cone genes in a mouse model of enhanced S-Cone Syndrome. PloS Genetics 1(2):0140 (2005)
• Sen, J., Harpavat, S., Peters, M.A., and Cepko, C.L. Retinoic acid regulates the expression of dorsoventral topographic guidance molecules in the chick retina. Development 132(23):5147-5159 (2005)
• Jadhav AP, Mason HA, Cepko CL. Notch 1 inhibits photoreceptor production in the developing mammalian retina. Development 133(5):913-923 (2006).
• Wildner, H., Muller, T., Cho, S-H., Brohl, D., Cepko, C.L., Guillemot, F., and Birchmeier, C. dILA neurons in the dorsal spinal cord are the product of terminal and non-terminal asymmetric progenitor cell divisions, and require Mash1 for their development. Development 133(11):2105-2113 (2006)
• Kuo, W.P., Liu, F., Trimarchi, J., Punzo, C., Lombardi, M., Sarang, J., Whipple, M.A., Maysuria, M., Serikawa, K., Lee, S.Y., McCrann, D., Kang, J., Shearstone, J.R., Burke, J., Park, D.J., Wang, X., Rector, T.L., Ricciardi-Castagnoli, P., Perrin, S., Choi, S., Bumgarner, R., Kim, J.H., Short III, G.F., Freeman, M.W., Seed, B., Jensen, R., Church, G.M., Hovig, E., Cepko, C.L., Park, P., Ohno-Machado, L., Jenssen, T-K. A sequence oriented comparison of gene expression measurements across different hybridization-based technologies. Nature Biotechnology : in print. (2006)