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Zheng-Yi Chen, D.Phil.

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Distinguished Poster Award at MGH Scientific Symposium
2004 - 2006
Pfizer/AFAR Innovations in Aging Research Program
Research Leader, The 2005 Scientific American 50

My research interests include 1). Molecular basis of deafness. 2). Functional genomics of hearing. 3). Inner ear hair cell regeneration. 4). Gene therapy for genetic hearing loss.

My work involves understanding the molecular basis of genetic deafness. I mapped and cloned one of the first human deafness genes, Norrie disease. I identified an allelic disorder, XFEVR, which is caused by mutations in Norrie gene. I characterized the mouse model for Norrie disease and demonstrated that the defects in the inner ear vasculature are the primary cause of deafness, which is one of the first cases of genetic deafness due to vasculature defects. I cloned two myosin genes, myosin VIIa and Myosin VIIb, and defects in myosin VIIa is responsible for Usher type Ib syndrome, a deafness-blindness syndrome. Further, we have shown that a recessive non-syndromic deafness is caused by mutations in prestin, an outer hair cell motor protein.

I am the first to use the functional genomics approach to study mammalian inner ear. I used microarray analysis to comprehensively study the gene expression of the developing mouse vestibular organ, the utricle, through its life cycle, and identified the major pathways involved at single-cell-type resolution. I am the first to comprehensively profile genes expressed in human inner ear. We have obtained the most complete survey of genes expressed in the mammalian inner ear, as well as in purified sensory hair cells, with the highest cellular resolution. This study laid the foundation for our work on hair cell regeneration and inner ear stem cell biology.

Mammalian inner ear lacks the capacity to regenerate hair cells. Using functional genomics approach, we identified the retinoblastoma gene (Rb1) as a gene essential in cell cycle exit and postmitotic maintenance of hair cells. We showed that when the Rb1 is deleted in the inner ear, normally postmitotic hair cell progenitor cells undergo proliferation, which then proceed normally with hair cell specification, differentiation and become functional.

We created a hair-cell-specific Rb1 deletion model, and showed that the adult Rb1-null vestibular hair cells continue to proliferate and are functional at both the cellular and the system levels. In postnatal cochlea, Rb1-null hair cells die due to impaired maturation. Thus, pRb is also required for cochlear hair cell maturation and survival. The study is the first to demonstrate that in mammals functional hair cells can be regenerated through cell cycle re-entry of existing hair cells, which has important implication in regeneration of other postmitotic cells including neurons. Using the chick hair cell regeneration model for expression profiling, we identified two pathways: c-Myc and Fgf, in hair cell regeneration. Using the zebrafish model, we demonstrate that spontaneous regeneration of the lateral line neuromast hair cells can be suppressed by blocking c-myc or Fgf pathways pharmacologically or genetically. One of the most important goals is to renew proliferation and hair cell regeneration in adult and aged mammalian inner ear. We have recently identified a mechanism by which adult and aged mammalian inner ear cells can re-enter cell cycle. Further under a proper condition the dividing cells can transdifferentiate to functional hair cells that are connected to ganglion neurons. This exciting work sets a stage to restore hearing in deaf animals.

1 in 500 newborns suffer from genetic hearing loss and no treatment is yet available. Recent progress in CRSIPR/Cas9 mediated genome editing makes it possible to permanently edit DNA sequences as new treatment for genetic hearing loss. In collaboration with David Liu at Harvard University, we have developed a method by which the key CRISPR enzyme Cas9 can be directly delivered into mammalian inner ear in vivo for genome editing. Further using a genetic hearing loss transgenic mouse model we have demonstrated that such approach could lead to hearing restoration. We are expanding this technology so it can be applied to treat different types of genetic hearing loss. This study has implication in the development of CRISPR/Cas9 to treat other types of genetic diseases.

The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. R01DC016875 (CHEN, ZHENG-YI) Jan 1, 2019 - Dec 31, 2023
    Development of Genome Editing as Treatment for Genetic Hearing Loss
    Role: Principal Investigator
  2. UG3TR002636 (CHEN, ZHENG-YI) Sep 18, 2018 - Jul 31, 2023
    Efficient in Vivo RNP-based Gene Editing in the Sensory Organ Inner Ear Using Bioreducible Lipid Nanoparticles
    Role: Principal Investigator
  3. R56DC006908 (CHEN, ZHENG-YI) Apr 1, 2005 - Jul 31, 2019
    Hair Cell Development
    Role: Principal Investigator
  4. R01DC006908 (CHEN, ZHENG-YI) Apr 1, 2005 - Mar 31, 2010
    Hair Cell Development
    Role: Principal Investigator
  5. R01DC004546 (CHEN, ZHENG-YI) Apr 1, 2001 - Mar 31, 2007
    Role: Principal Investigator

Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Scheffer DI, Shen J, Corey DP, Chen ZY. Gene Expression by Mouse Inner Ear Hair Cells during Development. J Neurosci. 2015 Apr 22; 35(16):6366-80. PMID: 25904789.
    Citations: 60     Fields:    Translation:AnimalsCells
  2. Scheffer DI, Zhang DS, Shen J, Indzhykulian A, Karavitaki KD, Xu YJ, Wang Q, Lin JJ, Chen ZY, Corey DP. XIRP2, an actin-binding protein essential for inner ear hair-cell stereocilia. Cell Rep. 2015 Mar 24; 10(11):1811-8. PMID: 25772365.
    Citations: 13     Fields:    Translation:AnimalsCells
  3. Li W, Wu J, Yang J, Sun S, Chai R, Chen ZY, Li H. Notch inhibition induces mitotically generated hair cells in mammalian cochleae via activating the Wnt pathway. Proc Natl Acad Sci U S A. 2015 Jan 06; 112(1):166-71. PMID: 25535395.
    Citations: 42     Fields:    Translation:AnimalsCells
  4. Zuris JA, Thompson DB, Shu Y, Guilinger JP, Bessen JL, Hu JH, Maeder ML, Joung JK, Chen ZY, Liu DR. Cationic lipid-mediated delivery of proteins enables efficient protein-based genome editing in vitro and in vivo. Nat Biotechnol. 2015 Jan; 33(1):73-80. PMID: 25357182.
    Citations: 185     Fields:    
  5. Li W, Sun S, Chen Y, Yu H, Chen ZY, Li H. Disrupting the interaction between retinoblastoma protein and Raf-1 leads to defects in progenitor cell proliferation and survival during early inner ear development. PLoS One. 2013; 8(12):e83726. PMID: 24391814.
    Citations: 1     Fields:    Translation:AnimalsCells
  6. Huang M, Kantardzhieva A, Scheffer D, Liberman MC, Chen ZY. Hair cell overexpression of Islet1 reduces age-related and noise-induced hearing loss. J Neurosci. 2013 Sep 18; 33(38):15086-94. PMID: 24048839.
    Citations: 8     Fields:    Translation:AnimalsCells
  7. Lu N, Chen Y, Wang Z, Chen G, Lin Q, Chen ZY, Li H. Sonic hedgehog initiates cochlear hair cell regeneration through downregulation of retinoblastoma protein. Biochem Biophys Res Commun. 2013 Jan 11; 430(2):700-5. PMID: 23211596.
    Citations: 7     Fields:    Translation:AnimalsCells
  8. Yan D, Xing Y, Ouyang X, Zhu J, Chen ZY, Lang H, Liu XZ. Analysis of miR-376 RNA cluster members in the mouse inner ear. Int J Exp Pathol. 2012 Dec; 93(6):450-7. PMID: 23136997.
    Citations: 9     Fields:    Translation:AnimalsCells
  9. Huang M, Sage C, Tang Y, Lee SG, Petrillo M, Hinds PW, Chen ZY. Overlapping and distinct pRb pathways in the mammalian auditory and vestibular organs. Cell Cycle. 2011 Jan 15; 10(2):337-51. PMID: 21239885.
    Citations: 16     Fields:    Translation:AnimalsCells
  10. Liu X, Han D, Li J, Han B, Ouyang X, Cheng J, Li X, Jin Z, Wang Y, Bitner-Glindzicz M, Kong X, Xu H, Kantardzhieva A, Eavey RD, Seidman CE, Seidman JG, Du LL, Chen ZY, Dai P, Teng M, Yan D, Yuan H. Loss-of-function mutations in the PRPS1 gene cause a type of nonsyndromic X-linked sensorineural deafness, DFN2. Am J Hum Genet. 2010 Jan; 86(1):65-71. PMID: 20021999.
    Citations: 29     Fields:    Translation:HumansAnimalsCells
  11. Zhu Y, Li Q, Chen ZY, Kun Y, Liu L, Liu X, Yuan H, Zhai S, Han D, Dai P. Mitochondrial haplotype and phenotype of 13 Chinese families may suggest multi-original evolution of mitochondrial C1494T mutation. Mitochondrion. 2009; 9(6):418-28.
  12. Huang M, Sage C, Li H, Xiang M, Heller S, Chen ZY. Diverse expression patterns of LIM-homeodomain transcription factors (LIM-HDs) in mammalian inner ear development. Dev Dyn. 2008 Nov; 237(11):3305-12. PMID: 18942141.
    Citations: 17     Fields:    Translation:AnimalsCells
  13. Edge AS, Chen ZY. Hair cell regeneration. Curr Opin Neurobiol. 2008 Aug; 18(4):377-82. PMID: 18929656.
    Citations: 33     Fields:    Translation:HumansAnimalsCells
  14. Williamson RE, Darrow KN, Giersch AB, Resendes BL, Huang M, Conrad GW, Chen ZY, Liberman MC, Morton CC, Tasheva ES. Expression studies of osteoglycin/mimecan (OGN) in the cochlea and auditory phenotype of Ogn-deficient mice. Hear Res. 2008 Mar; 237(1-2):57-65. PMID: 18243607.
    Citations: 8     Fields:    Translation:HumansAnimals
  15. Scheffer D, Sage C, Plazas PV, Huang M, Wedemeyer C, Zhang DS, Chen ZY, Elgoyhen AB, Corey DP, Pingault V. The a1 subunit of nicotinic acetylcholine receptors in the inner ear: transcriptional regulation by ATOH1 and co-expression with the ? subunit in hair cells. J Neurochem. 2007 Dec; 103(6):2651-64. PMID: 17961150.
    Citations: 10     Fields:    Translation:AnimalsCells
  16. Scheffe D, Sage C, Plazas PV, Huang MQ, Zhang DS, Chen ZY, Elgoyhen AB, Corey DP, Pingault V. The α1 subunit of nicotinic acetylcholine receptors in the inner ear: transcriptional regulation by ATOH1 and co-expression with the g subunit in hair cells. J Neurochem. 2007; (Epub ahead of print).
  17. Chen ZY. Cell cycle, differentiation and regeneration: where to begin? Cell Cycle. 2006 Nov; 5(22):2609-12. PMID: 17106260.
    Citations: 8     Fields:    Translation:HumansAnimalsCells
  18. Sage C, Huang M, Vollrath MA, Brown MC, Hinds PW, Corey DP, Vetter DE, Chen ZY. Essential role of retinoblastoma protein in mammalian hair cell development and hearing. Proc Natl Acad Sci U S A. 2006 May 09; 103(19):7345-50. PMID: 16648263.
    Citations: 66     Fields:    Translation:AnimalsCells
  19. Yan D, Li F, Hall ML, Sage C, Hu WH, Giallourakis C, Upadhyay G, Ouyang XM, Du LL, Bethea JR, Chen ZY, Yajnik V, Liu XZ. An isoform of GTPase regulator DOCK4 localizes to the stereocilia in the inner ear and binds to harmonin (USH1C). J Mol Biol. 2006 03 31; 357(3):755-64. PMID: 16464467.
    Citations: 12     Fields:    Translation:HumansAnimalsCells
  20. Sage C, Huang M, Karimi K, Gutierrez G, Vollrath MA, Zhang DS, García-Añoveros J, Hinds PW, Corwin JT, Corey DP, Chen ZY. Proliferation of functional hair cells in vivo in the absence of the retinoblastoma protein. Science. 2005 Feb 18; 307(5712):1114-8. PMID: 15653467.
    Citations: 97     Fields:    Translation:AnimalsCells
  21. Li H, Liu H, Sage C, Huang M, Chen ZY, Heller S. Islet-1 expression in the developing chicken inner ear. J Comp Neurol. 2004 Sep 06; 477(1):1-10. PMID: 15281076.
    Citations: 21     Fields:    Translation:AnimalsCells
  22. Chen ZY. Applications of genomics in the inner ear. Pharmacogenomics. 2003 Nov; 4(6):735-45. PMID: 14596637.
    Citations:    Fields:    Translation:HumansAnimals
  23. Liu XZ, Ouyang XM, Xia XJ, Zheng J, Pandya A, Li F, Du LL, Welch KO, Petit C, Smith RJ, Webb BT, Yan D, Arnos KS, Corey D, Dallos P, Nance WE, Chen ZY. Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss. Hum Mol Genet. 2003 May 15; 12(10):1155-62. PMID: 12719379.
    Citations: 65     Fields:    Translation:HumansCells
  24. Chen ZY, Corey DP. Understanding inner ear development with gene expression profiling. J Neurobiol. 2002 Nov 05; 53(2):276-85. PMID: 12382281.
    Citations: 7     Fields:    Translation:HumansAnimals
  25. Blanton SH, Liang CY, Cai MW, Pandya A, Du LL, Landa B, Mummalanni S, Li KS, Chen ZY, Qin XN, Liu YF, Balkany T, Nance WE, Liu XZ. A novel locus for autosomal dominant non-syndromic deafness (DFNA41) maps to chromosome 12q24-qter. J Med Genet. 2002 Aug; 39(8):567-70. PMID: 12161595.
    Citations: 10     Fields:    Translation:HumansCells
  26. Chen ZY, Corey DP. An inner ear gene expression database. J Assoc Res Otolaryngol. 2002 Jun; 3(2):140-8. PMID: 12162364.
    Citations: 17     Fields:    Translation:Animals
  27. Rehm HL, Zhang DS, Brown MC, Burgess B, Halpin C, Berger W, Morton CC, Corey DP, Chen ZY. Vascular defects and sensorineural deafness in a mouse model of Norrie disease. J Neurosci. 2002 Jun 01; 22(11):4286-92. PMID: 12040033.
    Citations: 34     Fields:    Translation:HumansAnimalsCells
  28. Liu XZ, Xia XJ, Adams J, Chen ZY, Welch KO, Tekin M, Ouyang XM, Kristiansen A, Pandya A, Balkany T, Arnos KS, Nance WE. Mutations in GJA1 (connexin 43) are associated with non-syndromic autosomal recessive deafness. Hum Mol Genet. 2001 Dec 01; 10(25):2945-51. PMID: 11741837.
    Citations: 20     Fields:    Translation:HumansAnimalsCells
  29. Chen ZY, Hasson T, Zhang DS, Schwender BJ, Derfler BH, Mooseker MS, Corey DP. Myosin-VIIb, a novel unconventional myosin, is a constituent of microvilli in transporting epithelia. Genomics. 2001 Mar 15; 72(3):285-96. PMID: 11401444.
    Citations: 17     Fields:    Translation:AnimalsCells
  30. Holt JR, Johns DC, Wang S, Chen ZY, Dunn RJ, Marban E, Corey DP. Functional expression of exogenous proteins in mammalian sensory hair cells infected with adenoviral vectors. J Neurophysiol. 1999 Apr; 81(4):1881-8. PMID: 10200223.
    Citations: 22     Fields:    Translation:AnimalsCells
  31. Kelley PM, Weston MD, Chen ZY, Orten DJ, Hasson T, Overbeck LD, Pinnt J, Talmadge CB, Ing P, Mooseker MS, Corey D, Sumegi J, Kimberling WJ. The genomic structure of the gene defective in Usher syndrome type Ib (MYO7A). Genomics. 1997 Feb 15; 40(1):73-9. PMID: 9070921.
    Citations: 7     Fields:    Translation:HumansCells
  32. Weston MD, Kelley PM, Overbeck LD, Wagenaar M, Orten DJ, Hasson T, Chen ZY, Corey D, Mooseker M, Sumegi J, Cremers C, Moller C, Jacobson SG, Gorin MB, Kimberling WJ. Myosin VIIA mutation screening in 189 Usher syndrome type 1 patients. Am J Hum Genet. 1996 Nov; 59(5):1074-83. PMID: 8900236.
    Citations: 29     Fields:    Translation:HumansCells
  33. Chen ZY, Hasson T, Kelley PM, Schwender BJ, Schwartz MF, Ramakrishnan M, Kimberling WJ, Mooseker MS, Corey DP. Molecular cloning and domain structure of human myosin-VIIa, the gene product defective in Usher syndrome 1B. Genomics. 1996 Sep 15; 36(3):440-8. PMID: 8884267.
    Citations: 29     Fields:    Translation:HumansAnimalsCells
  34. Hasson T, Skowron JF, Gilbert DJ, Avraham KB, Perry WL, Bement WM, Anderson BL, Sherr EH, Chen ZY, Greene LA, Ward DC, Corey DP, Mooseker MS, Copeland NG, Jenkins NA. Mapping of unconventional myosins in mouse and human. Genomics. 1996 Sep 15; 36(3):431-9. PMID: 8884266.
    Citations: 8     Fields:    Translation:HumansAnimals
  35. Battinelli EM, Boyd Y, Craig IW, Breakefield XO, Chen ZY. Characterization and mapping of the mouse NDP (Norrie disease) locus (Ndp). Mamm Genome. 1996 Feb; 7(2):93-7. PMID: 8835523.
    Citations: 1     Fields:    Translation:HumansAnimalsCells
  36. Black GC, Coleman MP, Chen ZY, Nemeth AH, Davies KE, Craig IW. A bidirectional YAC walk from the Norrie disease (NDP) locus. Genomics. 1995 Feb 10; 25(3):644-9. PMID: 7759098.
    Citations:    Fields:    Translation:HumansCells
  37. Schuback DE, Chen ZY, Craig IW, Breakefield XO, Sims KB. Mutations in the Norrie disease gene. Hum Mutat. 1995; 5(4):285-92. PMID: 7627181.
    Citations: 13     Fields:    Translation:HumansCells
  38. Chen ZY, Denney RM, Breakefield XO. Norrie disease and MAO genes: nearest neighbors. Hum Mol Genet. 1995; 4 Spec No:1729-37. PMID: 8541872.
    Citations: 5     Fields:    Translation:HumansAnimalsCells
  39. Bergen A-AB, Berger W, Chen ZY, Diergaarde,P, Battinelli EM, Warburg M, Bleeker-Wagemakers LM, Ropers HH, Craig IW. Norrie disease. Molecular Genetics of Inherited Eye Disorders (Wright AF and Jay B, ed). 1994; 321-338.
  40. Chen ZY, Battinelli EM, Fielder A, Bundey S, Sims K, Breakefield XO, Craig IW. A mutation in the Norrie disease gene (NDP) associated with X-linked familial exudative vitreoretinopathy. Nat Genet. 1993 Oct; 5(2):180-3. PMID: 8252044.
    Citations: 63     Fields:    Translation:HumansCells
  41. Chen ZY, Battinelli EM, Woodruff G, Young I, Breakefield XO, Craig IW. Characterization of a mutation within the NDP gene in a family with a manifesting female carrier. Hum Mol Genet. 1993 Oct; 2(10):1727-9. PMID: 8268931.
    Citations: 6     Fields:    Translation:HumansCells
  42. Chen ZY, Battinelli EM, Hendriks RW, Powell JF, Middleton-Price H, Sims KB, Breakefield XO, Craig IW. Norrie disease gene: characterization of deletions and possible function. Genomics. 1993 May; 16(2):533-5. PMID: 8314592.
    Citations: 6     Fields:    Translation:HumansAnimalsCells
  43. Hendriks RW, Chen ZY, Hinds H, Schuurman RK, Craig IW. Carrier detection in X-linked immunodeficiencies. I: A PCR-based X chromosome inactivation assay at the MAOA locus. Immunodeficiency. 1993; 4(1-4):209-11. PMID: 8167702.
    Citations:    Fields:    Translation:HumansCells
  44. Hinds H, Craig IW, Chen ZY, Kraakman ME, Schuurman RK, Hendriks RW. Carrier detection in X-linked immunodeficiencies. II: An X inactivation assay based on differential methylation of a line-1 repeat at the DXS255 locus. Immunodeficiency. 1993; 4(1-4):213-5. PMID: 8167703.
    Citations:    Fields:    Translation:HumansCells
  45. Breakefield XO, Chen ZY, Tivol E, Shalish C, Craig IW. Molecular genetics and inheritance of human MAO-A and MAO-B. Monoamine Oxidase: Its Role in Normal and Disease States. 1993; 95-112.
  46. Hendriks RW, Chen ZY, Hinds H, Schuurman RK, Craig IW. An X chromosome inactivation assay based on differential methylation of a CpG island coupled to a VNTR polymorphism at the 5' end of the monoamine oxidase A gene. Hum Mol Genet. 1992 Nov; 1(8):662. PMID: 1301186.
    Citations: 3     Fields:    Translation:Cells
  47. Hendriks RW, Hinds H, Chen ZY, Craig IW. The hypervariable DXS255 locus contains a LINE-1 repetitive element with a CpG island that is extensively methylated only on the active X chromosome. Genomics. 1992 Nov; 14(3):598-603. PMID: 1385307.
    Citations: 11     Fields:    Translation:HumansCells
  48. Chen ZY, Powell JF, Hsu YP, Breakefield XO, Craig IW. Organization of the human monoamine oxidase genes and long-range physical mapping around them. Genomics. 1992 Sep; 14(1):75-82. PMID: 1427833.
    Citations: 8     Fields:    Translation:HumansCells
  49. Hendriks RW, Chen ZY, Hinds H, Schuurman RK, Craig IW. An X chromosome inactivation assay based on differential methylation of a CpG island coupled to a VNTR polymorphism at the 5' end of the monoamine oxidase A gene. Hum Mol Genet. 1992 Jun; 1(3):187-94. PMID: 1303176.
    Citations: 7     Fields:    Translation:HumansCells
  50. Chen ZY, Hendriks RW, Jobling MA, Powell JF, Breakefield XO, Sims KB, Craig IW. Isolation and characterization of a candidate gene for Norrie disease. Nat Genet. 1992 Jun; 1(3):204-8. PMID: 1303236.
    Citations: 27     Fields:    Translation:HumansCells
  51. Chen ZY, Sims KB, Coleman M, Donnai D, Monaco A, Breakefield XO, Davies KE, Craig IW. Characterization of a YAC containing part or all of the Norrie disease locus. Hum Mol Genet. 1992 Jun; 1(3):161-4. PMID: 1303171.
    Citations: 2     Fields:    Translation:HumansCells
  52. Sims KB, Lebo RV, Benson G, Shalish C, Schuback D, Chen ZY, Bruns G, Craig IW, Golbus MS, Breakefield XO. The Norrie disease gene maps to a 150 kb region on chromosome Xp11.3. Hum Mol Genet. 1992 May; 1(2):83-9. PMID: 1301161.
    Citations: 5     Fields:    Translation:HumansCells
  53. Zheng-Yi Chen. Molecular Study of Human Sex Chromosomes. 1992.
  54. Chen ZY, Hotamisligil GS, Huang JK, Wen L, Ezzeddine D, Aydin-Muderrisoglu N, Powell JF, Huang RH, Breakefield XO, Craig I, et al. Structure of the human gene for monoamine oxidase type A. Nucleic Acids Res. 1991 Aug 25; 19(16):4537-41. PMID: 1886775.
    Citations: 9     Fields:    Translation:HumansCells
  55. Laval SH, Chen ZY, Boyd Y. The properdin structural locus (Pfc) lies close to the locus for tissue inhibitor of metallothionine proteases (Timp) on the mouse X chromosome. Genomics. 1991 Aug; 10(4):1030-4. PMID: 1916808.
    Citations: 6     Fields:    Translation:AnimalsCells
  56. Black GC, Chen ZY, Craig IW, Powell JF. Dinucleotide repeat polymorphism at the MAOA locus. Nucleic Acids Res. 1991 Feb 11; 19(3):689. PMID: 2011543.
    Citations: 23     Fields:    Translation:HumansCells
  57. Riley S, Black G, Chen ZY, Hatchwell E, Lorenz B, Meitinger T, Powell J, Wittwer B, Craig IW. An approach to cloning the proximal locus for X-linked retinitis pigmentosa. Degenerative Retinopathies: Advances in Clinical and Genetic Research. 1991; 119-128.
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Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.