Constance Cepko

Inducted in 2009 for her contributions to our understanding of the development of the central nervous system and diseases that result in blindness.

Constance (Connie) Cepko and her colleagues study the mechanisms that cells use when they choose their fate during the development of the central nervous system. Their studies focus on the retina, a tractable model of the central nervous system, and on the mechanisms that lead to the death of retinal cells, which are frequently the target of diseases that lead to blindness.

Constance Cepko is searching for a way to keep retinal cells alive in patients with a genetic disease that kills off cells important to vision. This cross-section of diseased retina tissue shows supportive cells (green), called Müller glia, and macrophages (red) migrating into the retina (all cells in blue) to remove dying rods.

Cepko's lab is developing viral vectors to deliver genes that promote better nutrition within cones to promote their survival in a degenerating retina.

Through basic research on disease and development genes in model organisms, Cepko's group is discovering how these genes work in humans. As the retina develops, its progenitor cells (the offspring of embryonic stem cells) have to decide when to divide, what types of nerve cells to become, and how many of each type to form. Her team discovered that early progenitors alter the ratio of cell types that are needed for early development, and late progenitors alter the ratio of cell types appropriate for the late stage. Cepko's group studies the molecular basis for these intrinsic differences between early and late progenitors, and how they intersect with patterning genes to determine a cell's fate.

She is now identifying genes that, when faulty, contribute to retinitis pigmentosa or macular degeneration, the leading cause of blindness in older people. In retinitis pigmentosa, the retina's light-sensing cells degenerate; Cepko is investigating why photoreceptor cells die. For example, her group is studying diseases in which intrinsic defects in a rod gene cause rod cells to die. They have found that cone cells starve and follow the death of the rods, even though the cones' genes are not defective. By understanding reasons for this, they hope to generate new ideas for treating macular degeneration. Cepko's group has also developed methods for relatively rapid alteration of the expression levels of genes in vivo.

Dr. Cepko is Professor of Genetics and Ophthalmology at Harvard Medical School, and a Howard Hughes Medical Institute investigator. She was inducted into the National Academy of Sciences in 2003. She received her Ph.D. in biology from the Massachusetts Institute of Technology, and her B.S. in biochemistry and microbiology from the University of Maryland.

She is the recipient of the David Cogan Award for Outstanding Young Investigator in Vision Research, and the Alcon Institute Research Award for Vision. She is also a member of the American Academy of Arts and Sciences, Association for Research in Vision and Ophthalmology, and Society for Neuroscience.