David E. Cobrinik, MD, PhD
|Title(s)||Associate Professor of Research Ophthalmology|
|Address||CHL 4650 W Sunset Blvd|
Los Angeles CA 90027
|Phone||+1 323 361 2275|
||1999||James S. McDonnell Foundation Scholar|
||1995||Susan G. Komen Breast Cancer Foundation Postdoctoral Fellow|
||1992||American Cancer Society Postdoctoral Fellow|
|1983||American Cancer Society Joseph S. Silber Pre-doctoral Fellow|
|1982||Oscar E. Schotté Award for Biological Research, Amherst College|
Our research seeks to improve understanding of retinal development and its relationship to retinal diseases. This goal stems from my long interest in a childhood retinal tumor called retinoblastoma, a cancer that develops in response to inactivation of the RB1 tumor suppressor gene and loss of functional pRB protein. One of our goals is to understand why cells of the retina but not other tissues routinely form cancers in response to pRB loss, and to use this knowledge to develop more effective therapies for retinoblastoma and other RB1-mutant cancers. We recently found that retinoblastomas arise from cone photoreceptor precursors, and that cone precursor-specific proliferation-related signaling pathways collaborate with pRB loss to enable tumorigenesis. This finding suggests that cone precursors signaling pathways can be targeted to suppress retinoblastoma development. Current studies aim to 1) define developmental signaling pathways that sensitize retinal cells to Rb loss, 2) define the step-by-step events through which Rb loss converts normal retinal cells to malignant retinoblastomas, and 3) target novel vulnerabilities in the pRB-deficient cone precursor circuitry.
With our colleagues at the CHLA Vision Center we also model retinal development and diseases using human pluripotent stem cells. We can produce normal-appearing developing retinas in vitro, opening the door to previously unimagined vision research opportunities. Current efforts aim to define similarities and differences between human retina produced in vitro and in vivo, and to thereby improve the verisimilitude of the in vitro retinal development model.