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profileEric Adam Pierce, M.D., Ph.D.

TitleProfessor of Ophthalmology
InstitutionMassachusetts Eye and Ear Infirmary
DepartmentOphthalmology
AddressMassachusetts Eye & Ear Infirmary
Ophthalmology, Room 563A
243 Charles St
Boston MA 02114
Phone617/573-6906
Fax617/573-6920
vCardDownload vCard (login for email)

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Please note that the correct contact information is as follows:
Tel: 617-573-6917
Fax: 617-573-6920
Email: eric_pierce@meei.harvard.edu


Molecular Genetics of Inherited Blindness
Inherited retinal degenerations such as retinitis pigmentosa (RP) are common causes of blindness. The overall goals of our research program are to improve our understanding of the molecular bases of inherited retinal degenerations and related cilia disorders so that rational therapies can be developed for these diseases.

We currently have 4 active research projects directed towards these goals:

1. The Biology and Diseases of Photoreceptor Sensory Cilia
Cilia are present on most cells in the human body. These structures are typically sensory organelles, and are involved in many critical aspects of cell biology and development. The photoreceptor sensory cilium (PSC) elaborated by each rod and cone photoreceptor cell of the retina is a classic example. Consistent with the importance of cilia in biology, mutations in genes that encode cilia components are common causes of disease. Mutations that cause inherited retinal degenerations, which are common causes of blindness, have been identified in genes encoding more than 40 PSC proteins to date. These disorders are characterized by PSC dysfunction, followed by degeneration and death of the photoreceptor cells, resulting in loss of vision.

We are interested in studying how photoreceptor sensory cilia are built and maintained, and how these processes are disrupted in disease. For example, while there has been notable progress identifying the genetic causes of inherited retinal degenerations and other cilia disorders, the genes that harbor mutations which cause disease in half of patients with inherited retinal degeneration remain to be identified. To help understand PSCs better, and facilitate identification of new retinal degeneration disease genes, we performed a series of proteomic analyses to identify all of the proteins in mouse photoreceptor sensory cilia. The results show that PSCs are made of almost 2000 proteins, including ~1500 proteins not detected in cilia from lower organisms. This database of PSC proteins has already proved to be very useful. For example, in the past year we have used the list of genes that encode novel PSC proteins to help identify one confirmed and four potential new retinal degeneration disease genes.

Retinitis Pigmentosa 1
Part of our work on PSCs is focused on the retinitis pigmentosa 1 (RP1) protein. Mutations in RP1 are a common cause of dominant RP, which is the most common form of inherited retinal degeneration. Work in our lab has found that the RP1 protein is a photoreceptor microtubule-associated protein that is required for the correct formation of PSCs. We are now working to identify proteins that interact with RP1 in order to further define how it participates in PSC formation, and study how its mutations lead to photoreceptor cell death. We are also beginning to test potential therapies for RP1 disease, including gene augmentation therapy, in point mutation Rp1 knockin mice.

2. RNA Splicing Factor Retinitis Pigmentosa
Mutations in genes that encode the RNA splicing factors are common causes retinitis pigmentosa (RP). Despite their prevalence, the pathogenesis of these disorders is not understood. The splicing factors affected, pre-mRNA processing factor (PRPF) 3, PRPF6, PRPF8, PRPF31 are highly conserved components of the spliceosome, the complex which excises introns from nascent RNA transcripts to generate mature mRNAs. Since RNA splicing is required in all cells, it is not clear how mutations in these ubiquitous proteins lead to retina-specific disease. We hypothesize that mutations in these RNA splicing factors disrupt RNA splicing and lead to the generation of aberrant transcripts and proteins in the retina and other tissues, one or more of which are pathogenic in the retina. We have generated Prpf3 and Prpf8 knockin mice, and obtained Prpf31 mutant mice from collaborators, to investigate the pathogenesis of the RNA splicing factor forms of RP. We are now using next generation sequencing based transcriptome analyses to identify aberrant mRNAs that may be pathogenic in these disorders.

3. Inherited Macular Degeneration
Age-related macular degeneration (AMD) is one of the most common cause of vision loss in developed countries. The most characteristic clinical finding in the retinas of patients with AMD is drusen, or extracellular deposits of protein, lipid and debris that accumulate underneath the retinal pigment epithelium (RPE). At present, the etiology of drusen in AMD is not known, and there are only limited treatments are available to prevent the progression of AMD. In order to gain insight into the pathogenesis of AMD, we are studying an inherited form of macular degeneration called Doyne honeycomb retinal dystrophy (DHRD)/Malattia Leventinese (ML). Both DHRD and ML are caused by a single mutation, Arg-345 to Trp (R345W), in the EFEMP1 or Fibulin-3 gene. We have used gene targeting techniques to introduce this mutation into the Efemp1 gene of mice. We have found that the Efemp1-R345W knockin mice develop AMD-like deposits under their retinas, and are now using proteomic analyses to study the pathogenesis of these lesions.

4. Oligonucleotide-Directed Gene Targeting and Gene Correction
The fundamental premise of this project that oligodeoxynucleotides (ODNs) can be used to introduce sequence-specific alterations into the genomic DNA of stem cells. In mouse embryonic stem (ES) cells, the goal of ODN-mediated gene targeting is to create knock-in mouse models of human disease. In adult and induced pluripotent stem cells (iPS), the use of ODNs is directed toward the therapeutic correction of pathogenic mutations in human disease genes. Results generated from our research and from other investigators in the past several years have demonstrated proof of principle for this approach. We are workinng to build on these successes to develop strategies for broad application of ODN-mediated gene correction for the treatment of human disease and ODN-mediated gene targeting for the generation of mouse models of disease.


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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.
R01EY026904     (PIERCE, ERIC A)Sep 30, 2017 - Jun 30, 2022
NIH/NEI
Genetic Causes and Genetic Modifiers of Inherited Retinal Degenerations
Role: Principal Investigator

R01EY020902     (PIERCE, ERIC A)Jul 1, 2010 - Mar 31, 2020
NIH/NEI
The Pathogenesis of RNA Splicing Factor Retinitis Pigmentosa
Role: Principal Investigator

R03EY013776     (PIERCE, ERIC A)Aug 1, 2001 - Jul 31, 2003
NIH/NEI
ANIMALS WITH TARGETED MUTATIONS IN PHOTORECEPTOR GENES
Role: Principal Investigator

R01EY012910     (PIERCE, ERIC A)Jul 8, 1999 - Jul 31, 2018
NIH/NEI
Novel Photoreceptor Proteins and Retinal Degenerations
Role: Principal Investigator

K11EY000343     (PIERCE, ERIC A)Jul 1, 1994 - Jun 30, 1999
NIH/NEI
BIOCHEMICAL BASIS OF RETINAL NEOVASCULARIZATION
Role: Principal Investigator

Collapse Bibliographic 
Collapse selected publications
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. Fernandez-Godino R, Bujakowska KM, Pierce EA. Changes in extracellular matrix cause RPE cells to make basal deposits and activate the alternative complement pathway. Hum Mol Genet. 2017 Oct 31. PMID: 29095988.
    View in: PubMed
  2. Men CJ, Bujakowska KM, Comander J, Place E, Bedoukian EC, Zhu X, Leroy BP, Fulton AB, Pierce EA. The importance of genetic testing as demonstrated by two cases of CACNA1F-associated retinal generation misdiagnosed as LCA. Mol Vis. 2017; 23:695-706. PMID: 29062221.
    View in: PubMed
  3. Comander J, Weigel-DiFranco C, Maher M, Place E, Wan A, Harper S, Sandberg MA, Navarro-Gomez D, Pierce EA. The Genetic Basis of Pericentral Retinitis Pigmentosa-A Form of Mild Retinitis Pigmentosa. Genes (Basel). 2017 Oct 05; 8(10). PMID: 28981474.
    View in: PubMed
  4. Bujakowska KM, Liu Q, Pierce EA. Photoreceptor Cilia and Retinal Ciliopathies. Cold Spring Harb Perspect Biol. 2017 Oct 03; 9(10). PMID: 28289063.
    View in: PubMed
  5. Liu MM, Farkas M, Spinnhirny P, Pevet P, Pierce E, Hicks D, Zack DJ. De novo assembly and annotation of the retinal transcriptome for the Nile grass rat (Arvicanthis ansorgei). PLoS One. 2017; 12(7):e0179061. PMID: 28759564.
    View in: PubMed
  6. Bujakowska KM, Fernandez-Godino R, Place E, Consugar M, Navarro-Gomez D, White J, Bedoukian EC, Zhu X, Xie HM, Gai X, Leroy BP, Pierce EA. Copy-number variation is an important contributor to the genetic causality of inherited retinal degenerations. Genet Med. 2017 Jun; 19(6):643-651. PMID: 27735924.
    View in: PubMed
  7. Arno G, Hull S, Carss K, Dev-Borman A, Chakarova C, Bujakowska K, van den Born I, Robson AG, Holder GE, Michaelides M, Cremers FP, Pierce E, Raymond FL, Moore AT, Webster AR. Reevaluation of the Retinal Dystrophy Due to Recessive Alleles of RGR With the Discovery of a Cis-Acting Mutation in CDHR1. Invest Ophthalmol Vis Sci. 2016 Sep 01; 57(11):4806-13. PMID: 27623334.
    View in: PubMed
  8. Sebag J, Sadun AA, Pierce EA. Paradigm Shifts in Ophthalmic Diagnostics. Trans Am Ophthalmol Soc. 2016 Aug; 114:WP1. PMID: 28008209.
    View in: PubMed
  9. Bennett J, Wellman J, Marshall KA, McCague S, Ashtari M, DiStefano-Pappas J, Elci OU, Chung DC, Sun J, Wright JF, Cross DR, Aravand P, Cyckowski LL, Bennicelli JL, Mingozzi F, Auricchio A, Pierce EA, Ruggiero J, Leroy BP, Simonelli F, High KA, Maguire AM. Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial. Lancet. 2016 Aug 13; 388(10045):661-72. PMID: 27375040.
    View in: PubMed
  10. Pan J, Liu S, Farkas M, Consugar M, Zack DJ, Kozak I, Arevalo JF, Pierce E, Qian J, Al Kahtani E. Serum molecular signature for proliferative diabetic retinopathy in Saudi patients with type 2 diabetes. Mol Vis. 2016; 22:636-45. PMID: 27307695; PMCID: PMC4902182.
  11. Fernandez-Godino R, Garland DL, Pierce EA. Isolation, culture and characterization of primary mouse RPE cells. Nat Protoc. 2016 Jul; 11(7):1206-18. PMID: 27281648.
    View in: PubMed
  12. Greenwald SH, Charette JR, Staniszewska M, Shi LY, Brown SD, Stone L, Liu Q, Hicks WL, Collin GB, Bowl MR, Krebs MP, Nishina PM, Pierce EA. Mouse Models of NMNAT1-Leber Congenital Amaurosis (LCA9) Recapitulate Key Features of the Human Disease. Am J Pathol. 2016 Jul; 186(7):1925-38. PMID: 27207593; PMCID: PMC4929402 [Available on 01/01/17].
  13. Falk MJ, Gai X, Shigematsu M, Vilardo E, Takase R, McCormick E, Christian T, Place E, Pierce EA, Consugar M, Gamper HB, Rossmanith W, Hou YM. A novel HSD17B10 mutation impairing the activities of the mitochondrial RNase P complex causes X-linked intractable epilepsy and neurodevelopmental regression. RNA Biol. 2016 May 03; 13(5):477-85. PMID: 26950678; PMCID: PMC4962811 [Available on 03/07/17].
  14. Poulter JA, Ali M, Gilmour DF, Rice A, Kondo H, Hayashi K, Mackey DA, Kearns LS, Ruddle JB, Craig JE, Pierce EA, Downey LM, Mohamed MD, Markham AF, Inglehearn CF, Toomes C. Mutations in TSPAN12 Cause Autosomal-Dominant Familial Exudative Vitreoretinopathy. Am J Hum Genet. 2016 Mar 03; 98(3):592. PMID: 28863275.
    View in: PubMed
  15. Fernandez-Godino R, Pierce EA, Garland DL. Extracellular Matrix Alterations and Deposit Formation in AMD. Adv Exp Med Biol. 2016; 854:53-8. PMID: 26427393.
    View in: PubMed
  16. Hafler BP, Comander J, Weigel DiFranco C, Place EM, Pierce EA. Course of Ocular Function in PRPF31 Retinitis Pigmentosa. Semin Ophthalmol. 2016; 31(1-2):49-52. PMID: 26959129.
    View in: PubMed
  17. Fernandez-Godino R, Garland DL, Pierce EA. A local complement response by RPE causes early-stage macular degeneration. Hum Mol Genet. 2015 Oct 01; 24(19):5555-69. PMID: 26199322; PMCID: PMC4572070 [Available on 10/01/16].
  18. Farkas MH, Au ED, Sousa ME, Pierce EA. RNA-Seq: Improving Our Understanding of Retinal Biology and Disease. Cold Spring Harb Perspect Med. 2015 Feb 26; 5(9):a017152. PMID: 25722474.
    View in: PubMed
  19. Pierce EA, Bennett J. The Status of RPE65 Gene Therapy Trials: Safety and Efficacy. Cold Spring Harb Perspect Med. 2015 Jan 29; 5(9):a017285. PMID: 25635059.
    View in: PubMed
  20. Bujakowska KM, Consugar M, Place E, Harper S, Lena J, Taub DG, White J, Navarro-Gomez D, Weigel DiFranco C, Farkas MH, Gai X, Berson EL, Pierce EA. Targeted exon sequencing in Usher syndrome type I. Invest Ophthalmol Vis Sci. 2014 Dec 02; 55(12):8488-96. PMID: 25468891; PMCID: PMC4280089.
  21. Consugar MB, Navarro-Gomez D, Place EM, Bujakowska KM, Sousa ME, Fonseca-Kelly ZD, Taub DG, Janessian M, Wang DY, Au ED, Sims KB, Sweetser DA, Fulton AB, Liu Q, Wiggs JL, Gai X, Pierce EA. Panel-based genetic diagnostic testing for inherited eye diseases is highly accurate and reproducible, and more sensitive for variant detection, than exome sequencing. Genet Med. 2015 Apr; 17(4):253-261. PMID: 25412400; PMCID: PMC4572572.
  22. Werdich XQ, Place EM, Pierce EA. Systemic diseases associated with retinal dystrophies. Semin Ophthalmol. 2014 Sep-Nov; 29(5-6):319-28. PMID: 25325857.
    View in: PubMed
  23. Bujakowska KM, Zhang Q, Siemiatkowska AM, Liu Q, Place E, Falk MJ, Consugar M, Lancelot ME, Antonio A, Lonjou C, Carpentier W, Mohand-Saïd S, den Hollander AI, Cremers FP, Leroy BP, Gai X, Sahel JA, van den Born LI, Collin RW, Zeitz C, Audo I, Pierce EA. Mutations in IFT172 cause isolated retinal degeneration and Bardet-Biedl syndrome. Hum Mol Genet. 2015 Jan 01; 24(1):230-42. PMID: 25168386; PMCID: PMC4326328.
  24. Farkas MH, Lew DS, Sousa ME, Bujakowska K, Chatagnon J, Bhattacharya SS, Pierce EA, Nandrot EF. Mutations in pre-mRNA processing factors 3, 8, and 31 cause dysfunction of the retinal pigment epithelium. Am J Pathol. 2014 Oct; 184(10):2641-52. PMID: 25111227; PMCID: PMC4188860.
  25. Song D, Grieco S, Li Y, Hunter A, Chu S, Zhao L, Song Y, DeAngelis RA, Shi LY, Liu Q, Pierce EA, Nishina PM, Lambris JD, Dunaief JL. A murine RP1 missense mutation causes protein mislocalization and slowly progressive photoreceptor degeneration. Am J Pathol. 2014 Oct; 184(10):2721-9. PMID: 25088982; PMCID: PMC4188862.
  26. Koboldt DC, Larson DE, Sullivan LS, Bowne SJ, Steinberg KM, Churchill JD, Buhr AC, Nutter N, Pierce EA, Blanton SH, Weinstock GM, Wilson RK, Daiger SP. Exome-based mapping and variant prioritization for inherited Mendelian disorders. Am J Hum Genet. 2014 Mar 06; 94(3):373-84. PMID: 24560519; PMCID: PMC3951946.
  27. Daiger SP, Bowne SJ, Sullivan LS, Blanton SH, Weinstock GM, Koboldt DC, Fulton RS, Larsen D, Humphries P, Humphries MM, Pierce EA, Chen R, Li Y. Application of next-generation sequencing to identify genes and mutations causing autosomal dominant retinitis pigmentosa (adRP). Adv Exp Med Biol. 2014; 801:123-9. PMID: 24664689; PMCID: PMC4121110.
  28. Wiggs JL, Pierce EA. Genetic testing for inherited eye disease: who benefits? JAMA Ophthalmol. 2013 Oct; 131(10):1265-6. PMID: 23949187.
    View in: PubMed
  29. Ehrenberg M, Pierce EA, Cox GF, Fulton AB. CRB1: one gene, many phenotypes. Semin Ophthalmol. 2013 Sep-Nov; 28(5-6):397-405. PMID: 24138049.
    View in: PubMed
  30. Gai X, Ghezzi D, Johnson MA, Biagosch CA, Shamseldin HE, Haack TB, Reyes A, Tsukikawa M, Sheldon CA, Srinivasan S, Gorza M, Kremer LS, Wieland T, Strom TM, Polyak E, Place E, Consugar M, Ostrovsky J, Vidoni S, Robinson AJ, Wong LJ, Sondheimer N, Salih MA, Al-Jishi E, Raab CP, Bean C, Furlan F, Parini R, Lamperti C, Mayr JA, Konstantopoulou V, Huemer M, Pierce EA, Meitinger T, Freisinger P, Sperl W, Prokisch H, Alkuraya FS, Falk MJ, Zeviani M. Mutations in FBXL4, encoding a mitochondrial protein, cause early-onset mitochondrial encephalomyopathy. Am J Hum Genet. 2013 Sep 05; 93(3):482-95. PMID: 23993194; PMCID: PMC3769923.
  31. Garland DL, Fernandez-Godino R, Kaur I, Speicher KD, Harnly JM, Lambris JD, Speicher DW, Pierce EA. Mouse genetics and proteomic analyses demonstrate a critical role for complement in a model of DHRD/ML, an inherited macular degeneration. Hum Mol Genet. 2014 Jan 01; 23(1):52-68. PMID: 23943789; PMCID: PMC3857944.
  32. Farkas MH, Grant GR, White JA, Sousa ME, Consugar MB, Pierce EA. Transcriptome analyses of the human retina identify unprecedented transcript diversity and 3.5 Mb of novel transcribed sequence via significant alternative splicing and novel genes. BMC Genomics. 2013 Jul 18; 14:486. PMID: 23865674; PMCID: PMC3924432.
  33. Testa F, Maguire AM, Rossi S, Pierce EA, Melillo P, Marshall K, Banfi S, Surace EM, Sun J, Acerra C, Wright JF, Wellman J, High KA, Auricchio A, Bennett J, Simonelli F. Three-year follow-up after unilateral subretinal delivery of adeno-associated virus in patients with Leber congenital Amaurosis type 2. Ophthalmology. 2013 Jun; 120(6):1283-91. PMID: 23474247; PMCID: PMC3674112.
  34. Wojno AP, Pierce EA, Bennett J. Seeing the light. Sci Transl Med. 2013 Mar 06; 5(175):175fs8. PMID: 23467559.
    View in: PubMed
  35. Falk MJ, Pierce EA, Consugar M, Xie MH, Guadalupe M, Hardy O, Rappaport EF, Wallace DC, LeProust E, Gai X. Mitochondrial disease genetic diagnostics: optimized whole-exome analysis for all MitoCarta nuclear genes and the mitochondrial genome. Discov Med. 2012 Dec; 14(79):389-99. PMID: 23272691; PMCID: PMC3923327.
  36. Liu Q, Collin RW, Cremers FP, den Hollander AI, van den Born LI, Pierce EA. Expression of wild-type Rp1 protein in Rp1 knock-in mice rescues the retinal degeneration phenotype. PLoS One. 2012; 7(8):e43251. PMID: 22927954; PMCID: PMC3424119.
  37. Falk MJ, Zhang Q, Nakamaru-Ogiso E, Kannabiran C, Fonseca-Kelly Z, Chakarova C, Audo I, Mackay DS, Zeitz C, Borman AD, Staniszewska M, Shukla R, Palavalli L, Mohand-Said S, Waseem NH, Jalali S, Perin JC, Place E, Ostrovsky J, Xiao R, Bhattacharya SS, Consugar M, Webster AR, Sahel JA, Moore AT, Berson EL, Liu Q, Gai X, Pierce EA. NMNAT1 mutations cause Leber congenital amaurosis. Nat Genet. 2012 Sep; 44(9):1040-5. PMID: 22842227; PMCID: PMC3454532.
  38. Zhang Q, Liu Q, Austin C, Drummond I, Pierce EA. Knockdown of ttc26 disrupts ciliogenesis of the photoreceptor cells and the pronephros in zebrafish. Mol Biol Cell. 2012 Aug; 23(16):3069-78. PMID: 22718903; PMCID: PMC3418303.
  39. Bennett J, Ashtari M, Wellman J, Marshall KA, Cyckowski LL, Chung DC, McCague S, Pierce EA, Chen Y, Bennicelli JL, Zhu X, Ying GS, Sun J, Wright JF, Auricchio A, Simonelli F, Shindler KS, Mingozzi F, High KA, Maguire AM. AAV2 gene therapy readministration in three adults with congenital blindness. Sci Transl Med. 2012 Feb 08; 4(120):120ra15. PMID: 22323828; PMCID: PMC4169122.
  40. Schrier SA, Wong LJ, Place E, Ji JQ, Pierce EA, Golden J, Santi M, Anninger W, Falk MJ. Mitochondrial tRNA-serine (AGY) m.C12264T mutation causes severe multisystem disease with cataracts. Discov Med. 2012 Feb; 13(69):143-50. PMID: 22369973; PMCID: PMC3618896.
  41. Bower M, Salomon R, Allanson J, Antignac C, Benedicenti F, Benetti E, Binenbaum G, Jensen UB, Cochat P, DeCramer S, Dixon J, Drouin R, Falk MJ, Feret H, Gise R, Hunter A, Johnson K, Kumar R, Lavocat MP, Martin L, Morinière V, Mowat D, Murer L, Nguyen HT, Peretz-Amit G, Pierce E, Place E, Rodig N, Salerno A, Sastry S, Sato T, Sayer JA, Schaafsma GC, Shoemaker L, Stockton DW, Tan WH, Tenconi R, Vanhille P, Vats A, Wang X, Warman B, Weleber RG, White SM, Wilson-Brackett C, Zand DJ, Eccles M, Schimmenti LA, Heidet L. Update of PAX2 mutations in renal coloboma syndrome and establishment of a locus-specific database. Hum Mutat. 2012 Mar; 33(3):457-66. PMID: 22213154.
    View in: PubMed
  42. Farkas MH, Grant GR, Pierce EA. Transcriptome analyses to investigate the pathogenesis of RNA splicing factor retinitis pigmentosa. Adv Exp Med Biol. 2012; 723:519-25. PMID: 22183372.
    View in: PubMed
  43. Grant GR, Farkas MH, Pizarro AD, Lahens NF, Schug J, Brunk BP, Stoeckert CJ, Hogenesch JB, Pierce EA. Comparative analysis of RNA-Seq alignment algorithms and the RNA-Seq unified mapper (RUM). Bioinformatics. 2011 Sep 15; 27(18):2518-28. PMID: 21775302; PMCID: PMC3167048.
  44. Iacovelli J, Zhao C, Wolkow N, Veldman P, Gollomp K, Ojha P, Lukinova N, King A, Feiner L, Esumi N, Zack DJ, Pierce EA, Vollrath D, Dunaief JL. Generation of Cre transgenic mice with postnatal RPE-specific ocular expression. Invest Ophthalmol Vis Sci. 2011 Mar; 52(3):1378-83. PMID: 21212186; PMCID: PMC3101664.
  45. Bowne SJ, Sullivan LS, Koboldt DC, Ding L, Fulton R, Abbott RM, Sodergren EJ, Birch DG, Wheaton DH, Heckenlively JR, Liu Q, Pierce EA, Weinstock GM, Daiger SP. Identification of disease-causing mutations in autosomal dominant retinitis pigmentosa (adRP) using next-generation DNA sequencing. Invest Ophthalmol Vis Sci. 2011 Jan 25; 52(1):494-503. PMID: 20861475; PMCID: PMC3053293.
  46. Davis EE, Zhang Q, Liu Q, Diplas BH, Davey LM, Hartley J, Stoetzel C, Szymanska K, Ramaswami G, Logan CV, Muzny DM, Young AC, Wheeler DA, Cruz P, Morgan M, Lewis LR, Cherukuri P, Maskeri B, Hansen NF, Mullikin JC, Blakesley RW, Bouffard GG, Gyapay G, Rieger S, Tönshoff B, Kern I, Soliman NA, Neuhaus TJ, Swoboda KJ, Kayserili H, Gallagher TE, Lewis RA, Bergmann C, Otto EA, Saunier S, Scambler PJ, Beales PL, Gleeson JG, Maher ER, Attié-Bitach T, Dollfus H, Johnson CA, Green ED, Gibbs RA, Hildebrandt F, Pierce EA, Katsanis N. TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum. Nat Genet. 2011 Mar; 43(3):189-96. PMID: 21258341; PMCID: PMC3071301.
  47. Cao H, Wu J, Lam S, Duan R, Newnham C, Molday RS, Graziotto JJ, Pierce EA, Hu J. Temporal and tissue specific regulation of RP-associated splicing factor genes PRPF3, PRPF31 and PRPC8--implications in the pathogenesis of RP. PLoS One. 2011 Jan 19; 6(1):e15860. PMID: 21283520; PMCID: PMC3023711.
  48. Graziotto JJ, Farkas MH, Bujakowska K, Deramaudt BM, Zhang Q, Nandrot EF, Inglehearn CF, Bhattacharya SS, Pierce EA. Three gene-targeted mouse models of RNA splicing factor RP show late-onset RPE and retinal degeneration. Invest Ophthalmol Vis Sci. 2011 Jan; 52(1):190-8. PMID: 20811066; PMCID: PMC3053274.
  49. Otto EA, Hurd TW, Airik R, Chaki M, Zhou W, Stoetzel C, Patil SB, Levy S, Ghosh AK, Murga-Zamalloa CA, van Reeuwijk J, Letteboer SJ, Sang L, Giles RH, Liu Q, Coene KL, Estrada-Cuzcano A, Collin RW, McLaughlin HM, Held S, Kasanuki JM, Ramaswami G, Conte J, Lopez I, Washburn J, Macdonald J, Hu J, Yamashita Y, Maher ER, Guay-Woodford LM, Neumann HP, Obermüller N, Koenekoop RK, Bergmann C, Bei X, Lewis RA, Katsanis N, Lopes V, Williams DS, Lyons RH, Dang CV, Brito DA, Dias MB, Zhang X, Cavalcoli JD, Nürnberg G, Nürnberg P, Pierce EA, Jackson PK, Antignac C, Saunier S, Roepman R, Dollfus H, Khanna H, Hildebrandt F. Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy. Nat Genet. 2010 Oct; 42(10):840-50. PMID: 20835237; PMCID: PMC2947620.
  50. Westfall JE, Hoyt C, Liu Q, Hsiao YC, Pierce EA, Page-McCaw PS, Ferland RJ. Retinal degeneration and failure of photoreceptor outer segment formation in mice with targeted deletion of the Joubert syndrome gene, Ahi1. J Neurosci. 2010 Jun 30; 30(26):8759-68. PMID: 20592197; PMCID: PMC2923804.
  51. Towns KV, Kipioti A, Long V, McKibbin M, Maubaret C, Vaclavik V, Ehsani P, Springell K, Kamal M, Ramesar RS, Mackey DA, Moore AT, Mukhopadhyay R, Webster AR, Black GC, O'Sullivan J, Bhattacharya SS, Pierce EA, Beggs JD, Inglehearn CF. Prognosis for splicing factor PRPF8 retinitis pigmentosa, novel mutations and correlation between human and yeast phenotypes. Hum Mutat. 2010 May; 31(5):E1361-76. PMID: 20232351.
    View in: PubMed
  52. Poulter JA, Ali M, Gilmour DF, Rice A, Kondo H, Hayashi K, Mackey DA, Kearns LS, Ruddle JB, Craig JE, Pierce EA, Downey LM, Mohamed MD, Markham AF, Inglehearn CF, Toomes C. Mutations in TSPAN12 cause autosomal-dominant familial exudative vitreoretinopathy. Am J Hum Genet. 2010 Feb 12; 86(2):248-53. PMID: 20159112; PMCID: PMC2820188.
  53. Daiger SP, Sullivan LS, Bowne SJ, Birch DG, Heckenlively JR, Pierce EA, Weinstock GM. Targeted high-throughput DNA sequencing for gene discovery in retinitis pigmentosa. Adv Exp Med Biol. 2010; 664:325-31. PMID: 20238032; PMCID: PMC2909649.
  54. Liu Q, Zhang Q, Pierce EA. Photoreceptor sensory cilia and inherited retinal degeneration. Adv Exp Med Biol. 2010; 664:223-32. PMID: 20238021; PMCID: PMC2888132.
  55. Simonelli F, Maguire AM, Testa F, Pierce EA, Mingozzi F, Bennicelli JL, Rossi S, Marshall K, Banfi S, Surace EM, Sun J, Redmond TM, Zhu X, Shindler KS, Ying GS, Ziviello C, Acerra C, Wright JF, McDonnell JW, High KA, Bennett J, Auricchio A. Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration. Mol Ther. 2010 Mar; 18(3):643-50. PMID: 19953081; PMCID: PMC2839440.
  56. Maguire AM, High KA, Auricchio A, Wright JF, Pierce EA, Testa F, Mingozzi F, Bennicelli JL, Ying GS, Rossi S, Fulton A, Marshall KA, Banfi S, Chung DC, Morgan JI, Hauck B, Zelenaia O, Zhu X, Raffini L, Coppieters F, De Baere E, Shindler KS, Volpe NJ, Surace EM, Acerra C, Lyubarsky A, Redmond TM, Stone E, Sun J, McDonnell JW, Leroy BP, Simonelli F, Bennett J. Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial. Lancet. 2009 Nov 07; 374(9701):1597-605. PMID: 19854499; PMCID: PMC4492302.
  57. Parry DA, Toomes C, Bida L, Danciger M, Towns KV, McKibbin M, Jacobson SG, Logan CV, Ali M, Bond J, Chance R, Swendeman S, Daniele LL, Springell K, Adams M, Johnson CA, Booth AP, Jafri H, Rashid Y, Banin E, Strom TM, Farber DB, Sharon D, Blobel CP, Pugh EN, Pierce EA, Inglehearn CF. Loss of the metalloprotease ADAM9 leads to cone-rod dystrophy in humans and retinal degeneration in mice. Am J Hum Genet. 2009 May; 84(5):683-91. PMID: 19409519; PMCID: PMC2681008.
  58. Liu Q, Saveliev A, Pierce EA. The severity of retinal degeneration in Rp1h gene-targeted mice is dependent on genetic background. Invest Ophthalmol Vis Sci. 2009 Apr; 50(4):1566-74. PMID: 19060274; PMCID: PMC2701263.
  59. Graziotto JJ, Inglehearn CF, Pack MA, Pierce EA. Decreased levels of the RNA splicing factor Prpf3 in mice and zebrafish do not cause photoreceptor degeneration. Invest Ophthalmol Vis Sci. 2008 Sep; 49(9):3830-8. PMID: 18552388.
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  60. Maguire AM, Simonelli F, Pierce EA, Pugh EN, Mingozzi F, Bennicelli J, Banfi S, Marshall KA, Testa F, Surace EM, Rossi S, Lyubarsky A, Arruda VR, Konkle B, Stone E, Sun J, Jacobs J, Dell'Osso L, Hertle R, Ma JX, Redmond TM, Zhu X, Hauck B, Zelenaia O, Shindler KS, Maguire MG, Wright JF, Volpe NJ, McDonnell JW, Auricchio A, High KA, Bennett J. Safety and efficacy of gene transfer for Leber's congenital amaurosis. N Engl J Med. 2008 May 22; 358(21):2240-8. PMID: 18441370; PMCID: PMC2829748.
  61. Flagler K, Alexeev V, Pierce EA, Igoucheva O. Site-specific gene modification by oligodeoxynucleotides in mouse bone marrow-derived mesenchymal stem cells. Gene Ther. 2008 Jul; 15(14):1035-48. PMID: 18337839.
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  62. Spellicy CJ, Daiger SP, Sullivan LS, Zhu J, Liu Q, Pierce EA, Bowne SJ. Characterization of retinal inosine monophosphate dehydrogenase 1 in several mammalian species. Mol Vis. 2007 Oct 03; 13:1866-72. PMID: 17960124.
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  63. Fu L, Garland D, Yang Z, Shukla D, Rajendran A, Pearson E, Stone EM, Zhang K, Pierce EA. The R345W mutation in EFEMP1 is pathogenic and causes AMD-like deposits in mice. Hum Mol Genet. 2007 Oct 15; 16(20):2411-22. PMID: 17666404.
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  64. Liu Q, Tan G, Levenkova N, Li T, Pugh EN, Rux JJ, Speicher DW, Pierce EA. The proteome of the mouse photoreceptor sensory cilium complex. Mol Cell Proteomics. 2007 Aug; 6(8):1299-317. PMID: 17494944; PMCID: PMC2128741.
  65. Jimeno D, Feiner L, Lillo C, Teofilo K, Goldstein LS, Pierce EA, Williams DS. Analysis of kinesin-2 function in photoreceptor cells using synchronous Cre-loxP knockout of Kif3a with RHO-Cre. Invest Ophthalmol Vis Sci. 2006 Nov; 47(11):5039-46. PMID: 17065525; PMCID: PMC1904505.
  66. Murphy BR, Moayedpardazi HS, Gewirtz AM, Diamond SL, Pierce EA. Delivery and mechanistic considerations for the production of knock-in mice by single-stranded oligonucleotide gene targeting. Gene Ther. 2007 Feb; 14(4):304-15. PMID: 17024103.
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  67. Bowne SJ, Liu Q, Sullivan LS, Zhu J, Spellicy CJ, Rickman CB, Pierce EA, Daiger SP. Why do mutations in the ubiquitously expressed housekeeping gene IMPDH1 cause retina-specific photoreceptor degeneration? Invest Ophthalmol Vis Sci. 2006 Sep; 47(9):3754-65. PMID: 16936083; PMCID: PMC2581456.
  68. Mechoulam H, Pierce EA. Expression and activation of STAT3 in ischemia-induced retinopathy. Invest Ophthalmol Vis Sci. 2005 Dec; 46(12):4409-16. PMID: 16303927.
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  69. Liu Q, Zuo J, Pierce EA. The retinitis pigmentosa 1 protein is a photoreceptor microtubule-associated protein. J Neurosci. 2004 Jul 21; 24(29):6427-36. PMID: 15269252; PMCID: PMC1904502.
  70. Peet JA, Bragin A, Calvert PD, Nikonov SS, Mani S, Zhao X, Besharse JC, Pierce EA, Knox BE, Pugh EN. Quantification of the cytoplasmic spaces of living cells with EGFP reveals arrestin-EGFP to be in disequilibrium in dark adapted rod photoreceptors. J Cell Sci. 2004 Jun 15; 117(Pt 14):3049-59. PMID: 15197244.
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  71. Ma H, Liu Q, Diamond SL, Pierce EA. Mouse embryonic stem cells efficiently lipofected with nuclear localization peptide result in a high yield of chimeric mice and retain germline transmission potency. Methods. 2004 Jun; 33(2):113-20. PMID: 15121165.
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  72. Liu Q, Lyubarsky A, Skalet JH, Pugh EN, Pierce EA. RP1 is required for the correct stacking of outer segment discs. Invest Ophthalmol Vis Sci. 2003 Oct; 44(10):4171-83. PMID: 14507858; PMCID: PMC1904498.
  73. Bowne SJ, Daiger SP, Malone KA, Heckenlively JR, Kennan A, Humphries P, Hughbanks-Wheaton D, Birch DG, Liu Q, Pierce EA, Zuo J, Huang Q, Donovan DD, Sullivan LS. Characterization of RP1L1, a highly polymorphic paralog of the retinitis pigmentosa 1 (RP1) gene. Mol Vis. 2003 Apr 24; 9:129-37. PMID: 12724644; PMCID: PMC2580755.
  74. Pierce EA, Liu Q, Igoucheva O, Omarrudin R, Ma H, Diamond SL, Yoon K. Oligonucleotide-directed single-base DNA alterations in mouse embryonic stem cells. Gene Ther. 2003 Jan; 10(1):24-33. PMID: 12525834.
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  75. Mechoulam H, Pierce EA. Retinopathy of prematurity: molecular pathology and therapeutic strategies. Am J Pharmacogenomics. 2003; 3(4):261-77. PMID: 12930159.
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  76. Gao J, Cheon K, Nusinowitz S, Liu Q, Bei D, Atkins K, Azimi A, Daiger SP, Farber DB, Heckenlively JR, Pierce EA, Sullivan LS, Zuo J. Progressive photoreceptor degeneration, outer segment dysplasia, and rhodopsin mislocalization in mice with targeted disruption of the retinitis pigmentosa-1 (Rp1) gene. Proc Natl Acad Sci U S A. 2002 Apr 16; 99(8):5698-703. PMID: 11960024; PMCID: PMC122834.
  77. Liu Q, Zhou J, Daiger SP, Farber DB, Heckenlively JR, Smith JE, Sullivan LS, Zuo J, Milam AH, Pierce EA. Identification and subcellular localization of the RP1 protein in human and mouse photoreceptors. Invest Ophthalmol Vis Sci. 2002 Jan; 43(1):22-32. PMID: 11773008; PMCID: PMC1963488.
  78. Yang S, Tutton S, Pierce E, Yoon K. Specific double-stranded RNA interference in undifferentiated mouse embryonic stem cells. Mol Cell Biol. 2001 Nov; 21(22):7807-16. PMID: 11604515; PMCID: PMC99950.
  79. Ashley SW, Perez A, Pierce EA, Brooks DC, Moore FD, Whang EE, Banks PA, Zinner MJ. Necrotizing pancreatitis: contemporary analysis of 99 consecutive cases. Ann Surg. 2001 Oct; 234(4):572-9; discussion 579-80. PMID: 11573050; PMCID: PMC1422080.
  80. Berson EL, Grimsby JL, Adams SM, McGee TL, Sweklo E, Pierce EA, Sandberg MA, Dryja TP. Clinical features and mutations in patients with dominant retinitis pigmentosa-1 (RP1). Invest Ophthalmol Vis Sci. 2001 Sep; 42(10):2217-24. PMID: 11527933.
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  81. Pierce EA. Pathways to photoreceptor cell death in inherited retinal degenerations. Bioessays. 2001 Jul; 23(7):605-18. PMID: 11462214.
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  82. Hata Y, Clermont A, Yamauchi T, Pierce EA, Suzuma I, Kagokawa H, Yoshikawa H, Robinson GS, Ishibashi T, Hashimoto T, Umeda F, Bursell SE, Aiello LP. Retinal expression, regulation, and functional bioactivity of prostacyclin-stimulating factor. J Clin Invest. 2000 Aug; 106(4):541-50. PMID: 10953029; PMCID: PMC380244.
  83. Jacobson SG, Cideciyan AV, Iannaccone A, Weleber RG, Fishman GA, Maguire AM, Affatigato LM, Bennett J, Pierce EA, Danciger M, Farber DB, Stone EM. Disease expression of RP1 mutations causing autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2000 Jun; 41(7):1898-908. PMID: 10845615.
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  84. Pierce EA, Quinn T, Meehan T, McGee TL, Berson EL, Dryja TP. Mutations in a gene encoding a new oxygen-regulated photoreceptor protein cause dominant retinitis pigmentosa. Nat Genet. 1999 Jul; 22(3):248-54. PMID: 10391211.
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  85. Sinha D, Esumi N, Jaworski C, Kozak CA, Pierce E, Wistow G. Cloning and mapping the mouse Crygs gene and non-lens expression of [gamma]S-crystallin. Mol Vis. 1998 Apr 30; 4:8. PMID: 9565648.
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  86. Young TL, Anthony DC, Pierce E, Foley E, Smith LE. Histopathology and vascular endothelial growth factor in untreated and diode laser-treated retinopathy of prematurity. J AAPOS. 1997 Jun; 1(2):105-10. PMID: 10875087.
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  87. Pierce EA, Foley ED, Smith LE. Regulation of vascular endothelial growth factor by oxygen in a model of retinopathy of prematurity. Arch Ophthalmol. 1996 Oct; 114(10):1219-28. PMID: 8859081.
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  88. Robinson GS, Pierce EA, Rook SL, Foley E, Webb R, Smith LE. Oligodeoxynucleotides inhibit retinal neovascularization in a murine model of proliferative retinopathy. Proc Natl Acad Sci U S A. 1996 May 14; 93(10):4851-6. PMID: 8643492; PMCID: PMC39368.
  89. Aiello LP, Pierce EA, Foley ED, Takagi H, Chen H, Riddle L, Ferrara N, King GL, Smith LE. Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc Natl Acad Sci U S A. 1995 Nov 07; 92(23):10457-61. PMID: 7479819; PMCID: PMC40630.
  90. Pierce EA, Mukai S. Controversies in the management of retinopathy of prematurity. Int Ophthalmol Clin. 1994; 34(3):121-48. PMID: 7960509.
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  91. Dinauer MC, Pierce EA, Erickson RW, Muhlebach TJ, Messner H, Orkin SH, Seger RA, Curnutte JT. Point mutation in the cytoplasmic domain of the neutrophil p22-phox cytochrome b subunit is associated with a nonfunctional NADPH oxidase and chronic granulomatous disease. Proc Natl Acad Sci U S A. 1991 Dec 15; 88(24):11231-5. PMID: 1763037; PMCID: PMC53108.
  92. Dinauer MC, Pierce EA, Bruns GA, Curnutte JT, Orkin SH. Human neutrophil cytochrome b light chain (p22-phox). Gene structure, chromosomal location, and mutations in cytochrome-negative autosomal recessive chronic granulomatous disease. J Clin Invest. 1990 Nov; 86(5):1729-37. PMID: 2243141; PMCID: PMC296926.
  93. Schleutermann D, Pierce E, Cantolino Sj, Naidoff M. Retinitis pigmentosa, autosomal dominant type: two kindreds. Birth Defects Orig Artic Ser. 1971 Mar; 7(3):178-9. PMID: 5173137.
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  94. Schleutermann D, Pierce E, Cantolino SJ, Naidoff M. Retinitis pigmentosa, autosomal recessive type: three kindreds. Birth Defects Orig Artic Ser. 1971 Mar; 7(3):180-2. PMID: 5173138.
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  95. Schleutermann D, Pierce E, Cantolino SJ, Naidoff M, Hussels IE. Retinitis pigmentosa, X-linked form: two kindreds. Birth Defects Orig Artic Ser. 1971 Mar; 7(3):183-4. PMID: 5173139.
    View in: PubMed
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