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David E. Cobrinik, MD, PhD

Title(s)Associate Professor of Research Ophthalmology
Phone+1 323 361 2275
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    Collapse Biography 
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    1996  - 1999James S. McDonnell Foundation Scholar
    1992  - 1995Susan G. Komen Breast Cancer Foundation Postdoctoral Fellow
    1989  - 1992American Cancer Society Postdoctoral Fellow
    1983American Cancer Society Joseph S. Silber Pre-doctoral Fellow
    1982Oscar E. Schotté Award for Biological Research, Amherst College

    Collapse Overview 
    Collapse Overview
    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.

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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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    1. Munier FL, Beck-Popovic M, Chantada GL, Cobrinik D, Kivelä TT, Lohmann D, Maeder P, Moll AC, Carcaboso AM, Moulin A, Schaiquevich P, Bergin C, Dyson PJ, Houghton S, Puccinelli F, Vial Y, Gaillard MC, Stathopoulos C. Conservative management of retinoblastoma: Challenging orthodoxy without compromising the state of metastatic grace. "Alive, with good vision and no comorbidity". Prog Retin Eye Res. 2019 Jun 05; 100764. PMID: 31173880.
      View in: PubMed
    2. Li Z, Qi DL, Singh HP, Zou Y, Shen B, Cobrinik D. A novel thyroid hormone receptor isoform, TRß2-46, promotes SKP2 expression and retinoblastoma cell proliferation. J Biol Chem. 2019 02 22; 294(8):2961-2969. PMID: 30643022.
      View in: PubMed
    3. Singh HP, Wang S, Stachelek K, Lee S, Reid MW, Thornton ME, Craft CM, Grubbs BH, Cobrinik D. Developmental stage-specific proliferation and retinoblastoma genesis in RB-deficient human but not mouse cone precursors. Proc Natl Acad Sci U S A. 2018 10 02; 115(40):E9391-E9400. PMID: 30213853.
      View in: PubMed
    4. Berry JL, Xu L, Kooi I, Murphree AL, Prabakar RK, Reid M, Stachelek K, Le BHA, Welter L, Reiser BJ, Chévez-Barrios P, Jubran R, Lee TC, Kim JW, Kuhn P, Cobrinik D, Hicks J. Genomic cfDNA Analysis of Aqueous Humor in Retinoblastoma Predicts Eye Salvage: The Surrogate Tumor Biopsy for Retinoblastoma. Mol Cancer Res. 2018 11; 16(11):1701-1712. PMID: 30061186.
      View in: PubMed
    5. Berry JL, Cobrinik D, Hicks J. Potential of Aqueous Humor as a Surrogate Tumor Biopsy for Retinoblastoma-Reply. JAMA Ophthalmol. 2018 05 01; 136(5):598. PMID: 29566117.
      View in: PubMed
    6. Berry JL, Xu L, Murphree AL, Krishnan S, Stachelek K, Zolfaghari E, McGovern K, Lee TC, Carlsson A, Kuhn P, Kim JW, Cobrinik D, Hicks J. Potential of Aqueous Humor as a Surrogate Tumor Biopsy for Retinoblastoma. JAMA Ophthalmol. 2017 11 01; 135(11):1221-1230. PMID: 29049475.
      View in: PubMed
    7. Xu XL, Li Z, Liu A, Fan X, Hu DN, Qi DL, Chitty DW, Jia R, Qui J, Wang JQ, Sharaf J, Zou J, Weiss R, Huang H, Joseph WJ, Ng L, Rosen R, Shen B, Reid MW, Forrest D, Abramson DH, Singer S, Cobrinik D, Jhanwar SC. SKP2 Activation by Thyroid Hormone Receptor ß2 Bypasses Rb-Dependent Proliferation in Rb-Deficient Cells. Cancer Res. 2017 12 15; 77(24):6838-6850. PMID: 28972075.
      View in: PubMed
    8. Browne AW, Arnesano C, Harutyunyan N, Khuu T, Martinez JC, Pollack HA, Koos DS, Lee TC, Fraser SE, Moats RA, Aparicio JG, Cobrinik D. Structural and Functional Characterization of Human Stem-Cell-Derived Retinal Organoids by Live Imaging. Invest Ophthalmol Vis Sci. 2017 07 01; 58(9):3311-3318. PMID: 28672397.
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    9. Qi DL, Cobrinik D. MDM2 but not MDM4 promotes retinoblastoma cell proliferation through p53-independent regulation of MYCN translation. Oncogene. 2017 03 30; 36(13):1760-1769. PMID: 27748758.
      View in: PubMed
    10. Li WL, Buckley J, Sanchez-Lara PA, Maglinte DT, Viduetsky L, Tatarinova TV, Aparicio JG, Kim JW, Au M, Ostrow D, Lee TC, O'Gorman M, 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 07; 18(4):480-93. PMID: 27155049.
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    11. Berry JL, Cobrinik D, Kim JW. Detection and Intraretinal Localization of an 'Invisible' Retinoblastoma Using Optical Coherence Tomography. Ocul Oncol Pathol. 2016 Apr; 2(3):148-52. PMID: 27239455.
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    12. Dimaras H, Corson TW, Cobrinik D, White A, Zhao J, Munier FL, Abramson DH, Shields CL, Chantada GL, Njuguna F, Gallie BL. Retinoblastoma. Nat Rev Dis Primers. 2015 08 27; 1:15021. PMID: 27189421.
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    13. Cobrinik D. Retinoblastoma Progression. EBioMedicine. 2015 Jul; 2(7):623-4. PMID: 26288828.
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    14. Xu XL, Singh HP, Wang L, Qi DL, Poulos BK, Abramson DH, Jhanwar SC, Cobrinik D. Rb suppresses human cone-precursor-derived retinoblastoma tumours. Nature. 2014 Oct 16; 514(7522):385-8. PMID: 25252974.
      View in: PubMed
    15. Cobrinik D, Ostrovnaya I, Hassimi M, Tickoo SK, Cheung IY, Cheung NK. Recurrent pre-existing and acquired DNA copy number alterations, including focal TERT gains, in neuroblastoma central nervous system metastases. Genes Chromosomes Cancer. 2013 Dec; 52(12):1150-66. PMID: 24123354.
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    16. Xing F, Persaud Y, Pratilas CA, Taylor BS, Janakiraman M, She QB, Gallardo H, Liu C, Merghoub T, Hefter B, Dolgalev I, Viale A, Heguy A, De Stanchina E, Cobrinik D, Bollag G, Wolchok J, Houghton A, Solit DB. Concurrent loss of the PTEN and RB1 tumor suppressors attenuates RAF dependence in melanomas harboring (V600E)BRAF. Oncogene. 2012 Jan 26; 31(4):446-57. PMID: 21725359.
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    17. Ciavarra G, Ho AT, Cobrinik D, Zacksenhaus E. Critical role of the Rb family in myoblast survival and fusion. PLoS One. 2011 Mar 10; 6(3):e17682. PMID: 21423694.
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    18. Xu XL, Lee TC, Offor N, Cheng C, Liu A, Fang Y, Jhanwar SC, Abramson DH, Cobrinik D. Tumor-associated retinal astrocytes promote retinoblastoma cell proliferation through production of IGFBP-5. Am J Pathol. 2010 Jul; 177(1):424-35. PMID: 20508032.
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    19. Wang H, Bauzon F, Ji P, Xu X, Sun D, Locker J, Sellers RS, Nakayama K, Nakayama KI, Cobrinik D, Zhu L. Skp2 is required for survival of aberrantly proliferating Rb1-deficient cells and for tumorigenesis in Rb1+/- mice. Nat Genet. 2010 Jan; 42(1):83-8. PMID: 19966802.
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    20. Xu XL, Fang Y, Lee TC, Forrest D, Gregory-Evans C, Almeida D, Liu A, Jhanwar SC, Abramson DH, Cobrinik D. Retinoblastoma has properties of a cone precursor tumor and depends upon cone-specific MDM2 signaling. Cell. 2009 Jun 12; 137(6):1018-31. PMID: 19524506.
      View in: PubMed
    21. Harb G, Vasavada RC, Cobrinik D, Stewart AF. The retinoblastoma protein and its homolog p130 regulate the G1/S transition in pancreatic beta-cells. Diabetes. 2009 Aug; 58(8):1852-62. PMID: 19509021.
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    22. Cobrinik D, Francis RO, Abramson DH, Lee TC. Rb induces a proliferative arrest and curtails Brn-2 expression in retinoblastoma cells. Mol Cancer. 2006 Dec 12; 5:72. PMID: 17163992.
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    23. Lee TC, Almeida D, Claros N, Abramson DH, Cobrinik D. Cell cycle-specific and cell type-specific expression of Rb in the developing human retina. Invest Ophthalmol Vis Sci. 2006 Dec; 47(12):5590-8. PMID: 17122153.
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    24. Elison JR, Cobrinik D, Claros N, Abramson DH, Lee TC. Small molecule inhibition of HDM2 leads to p53-mediated cell death in retinoblastoma cells. Arch Ophthalmol. 2006 Sep; 124(9):1269-75. PMID: 16966622.
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    25. Cobrinik D. Pocket proteins and cell cycle control. Oncogene. 2005 Apr 18; 24(17):2796-809. PMID: 15838516.
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    26. MacLean HE, Guo J, Knight MC, Zhang P, Cobrinik D, Kronenberg HM. The cyclin-dependent kinase inhibitor p57(Kip2) mediates proliferative actions of PTHrP in chondrocytes. J Clin Invest. 2004 May; 113(9):1334-43. PMID: 15124025.
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    27. Fang W, Mori T, Cobrinik D. Regulation of PML-dependent transcriptional repression by pRB and low penetrance pRB mutants. Oncogene. 2002 Aug 15; 21(36):5557-65. PMID: 12165854.
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    28. Laplantine E, Rossi F, Sahni M, Basilico C, Cobrinik D. FGF signaling targets the pRb-related p107 and p130 proteins to induce chondrocyte growth arrest. J Cell Biol. 2002 Aug 19; 158(4):741-50. PMID: 12177046.
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    29. Rossi F, MacLean HE, Yuan W, Francis RO, Semenova E, Lin CS, Kronenberg HM, Cobrinik D. p107 and p130 Coordinately regulate proliferation, Cbfa1 expression, and hypertrophic differentiation during endochondral bone development. Dev Biol. 2002 Jul 15; 247(2):271-85. PMID: 12086466.
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    30. Liberto M, Cobrinik D, Minden A. Rho regulates p21(CIP1), cyclin D1, and checkpoint control in mammary epithelial cells. Oncogene. 2002 Feb 28; 21(10):1590-9. PMID: 11896588.
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    31. Antman K, Benson MC, Chabot J, Cobrinik D, Grann VR, Jacobson JS, Joe AK, Katz AE, Kelly K, Neugut AI, Russo D, Tiersten A, Weinstein IB. Complementary and alternative medicine: the role of the cancer center. J Clin Oncol. 2001 Sep 15; 19(18 Suppl):55S-60S. PMID: 11560974.
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    32. Cheng L, Rossi F, Fang W, Mori T, Cobrinik D. Cdk2-dependent phosphorylation and functional inactivation of the pRB-related p130 protein in pRB(-), p16INK4A(+) tumor cells. J Biol Chem. 2000 Sep 29; 275(39):30317-25. PMID: 10906146.
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    33. Liberto M, Cobrinik D. Growth factor-dependent induction of p21(CIP1) by the green tea polyphenol, epigallocatechin gallate. Cancer Lett. 2000 Jun 30; 154(2):151-61. PMID: 10806303.
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    34. Hurford RK, Cobrinik D, Lee MH, Dyson N. pRB and p107/p130 are required for the regulated expression of different sets of E2F responsive genes. Genes Dev. 1997 Jun 01; 11(11):1447-63. PMID: 9192872.
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    35. Cobrinik D, Lee MH, Hannon G, Mulligan G, Bronson RT, Dyson N, Harlow E, Beach D, Weinberg RA, Jacks T. Shared role of the pRB-related p130 and p107 proteins in limb development. Genes Dev. 1996 Jul 01; 10(13):1633-44. PMID: 8682294.
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    36. Cobrinik D. Regulatory interactions among E2Fs and cell cycle control proteins. Curr Top Microbiol Immunol. 1996; 208:31-61. PMID: 8575212.
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    37. Sardet C, Vidal M, Cobrinik D, Geng Y, Onufryk C, Chen A, Weinberg RA. E2F-4 and E2F-5, two members of the E2F family, are expressed in the early phases of the cell cycle. Proc Natl Acad Sci U S A. 1995 Mar 14; 92(6):2403-7. PMID: 7892279.
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    38. Cobrinik D, Whyte P, Peeper DS, Jacks T, Weinberg RA. Cell cycle-specific association of E2F with the p130 E1A-binding protein. Genes Dev. 1993 Dec; 7(12A):2392-404. PMID: 8253385.
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    39. Cobrinik D, Dowdy SF, Hinds PW, Mittnacht S, Weinberg RA. The retinoblastoma protein and the regulation of cell cycling. Trends Biochem Sci. 1992 Aug; 17(8):312-5. PMID: 1412705.
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    40. Aiyar A, Cobrinik D, Ge Z, Kung HJ, Leis J. Interaction between retroviral U5 RNA and the T psi C loop of the tRNA(Trp) primer is required for efficient initiation of reverse transcription. J Virol. 1992 Apr; 66(4):2464-72. PMID: 1548772.
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    41. Cobrinik D, Aiyar A, Ge Z, Katzman M, Huang H, Leis J. Overlapping retrovirus U5 sequence elements are required for efficient integration and initiation of reverse transcription. J Virol. 1991 Jul; 65(7):3864-72. PMID: 1710292.
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    42. Cobrinik D, Soskey L, Leis J. A retroviral RNA secondary structure required for efficient initiation of reverse transcription. J Virol. 1988 Oct; 62(10):3622-30. PMID: 2458484.
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    43. Terry R, Soltis DA, Katzman M, Cobrinik D, Leis J, Skalka AM. Properties of avian sarcoma-leukosis virus pp32-related pol-endonucleases produced in Escherichia coli. J Virol. 1988 Jul; 62(7):2358-65. PMID: 2836618.
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    44. Cobrinik D, Katz R, Terry R, Skalka AM, Leis J. Avian sarcoma and leukosis virus pol-endonuclease recognition of the tandem long terminal repeat junction: minimum site required for cleavage is also required for viral growth. J Virol. 1987 Jun; 61(6):1999-2008. PMID: 3033327.
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    45. Duyk G, Longiaru M, Cobrinik D, Kowal R, deHaseth P, Skalka AM, Leis J. Circles with two tandem long terminal repeats are specifically cleaved by pol gene-associated endonuclease from avian sarcoma and leukosis viruses: nucleotide sequences required for site-specific cleavage. J Virol. 1985 Nov; 56(2):589-99. PMID: 2414465.
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