David E. Cobrinik
Associate Professor
Research Ophthalmology
Keck School of Medicine
United States of America
Biography
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.
Research Interest
Research Ophthalmology
Publications
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Judkins A, Cobrinik D, Triche TJ. A Rapid and Sensitive Next-Generation Sequencing Method to Detect RB1 Mutations Improves Care for Retinoblastoma Patients and Their Families. J Mol Diagn. 2016 Jul;18(4):480-93.
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Qi DL, Cobrinik D. MDM2 but not MDM4 promotes retinoblastoma cell proliferation through p53-independent regulation of MYCN translation. Oncogene. 2017 Mar 30;36(13):1760-1769.