Menu UF Health Home Menu
 

Astra Dinculescu, Ph.D.

Academic Title

Assistant Professor

Contact Information

(352) 273-7548 (phone)
(352) 392-0573 (fax)
astra@ufl.edu

Lab

R1-236

About

Dr. Dinculescu received her Ph.D. in Biochemistry from University of Florida in 2002. Her main research focus is on developing therapeutic approaches for Usher syndrome type III (USH3A), an autosomal recessive disorder caused by mutations in Clarin-1 (CLRN1) gene, leading to progressive retinal degeneration and hearing loss. In addition, she studies the pathological processes affecting the neural retina/retinal pigment epithelium (RPE)/Bruch’s membrane interface, and the mechanisms leading to the formation of drusen in age-related macular degeneration. She developed an interest in complement C1q tumor necrosis factor-related protein-5 (C1QTNF5) following her discovery that mutant S163R C1QTNF5 forms globular aggregates in the RPE, and accumulates as thick, widespread, extracellular RPE basal laminar deposits. She is currently testing various approaches aimed at preventing the abnormal protein aggregation in RPE, by modulating chaperone expression and targeting the autophagy pathway.

Current Funding

  • R01 EY026559-01A1 (09/01/2016-08/31/2021)Title: “Clarin-1 retinal function and therapeutic implications for USH3”

    The goal of this project is to identify Clarin-1 cellular localization and its protein binding partners, in order to develop rational therapeutic approaches to prevent the vision and hearing loss in patients with USH3 disorder.

Publications

  • Dinculescu A, Stupay RM, Deng WT, Dyka FM, Min SH, Boye SL, Chiodo VA, Abrahan CE, Zhu P, Li Q, Strettoi E, Novelli E, Nagel-Wolfrum K, Wolfrum U, Smith WC and Hauswirth WW (2016) AAV-Mediated Clarin-1 Expression in the Mouse Retina: Implications for USH3A Gene Therapy. PLoS One 11:e0148874. doi: 10.1371/journal.pone.0148874
  • Dinculescu A, Min SH, Dyka FM, Deng WT, Stupay RM, Chiodo V, Smith WC and Hauswirth WW (2015) Pathological Effects of Mutant C1QTNF5 (S163R) Expression in Murine Retinal Pigment Epithelium. Invest Ophthalmol Vis Sci 56:6971-80. doi: 10.1167/iovs.15-17166
  • Deng WT, Dyka FM, Dinculescu A, Li J, Zhu P, Chiodo VA, Boye SL, Conlon TJ, Erger K, Cossette T and Hauswirth WW (2015) Stability and Safety of an AAV Vector for Treating RPGR-ORF15 X-Linked Retinitis Pigmentosa. Hum Gene Ther 26:593-602. doi: 10.1089/hum.2015.035
  • Mowat FM, Gornik KR, Dinculescu A, Boye SL, Hauswirth WW, Petersen-Jones SM and Bartoe JT (2014) Tyrosine capsid-mutant AAV vectors for gene delivery to the canine retina from a subretinal or intravitreal approach. Gene Ther 21:96-105. doi: 10.1038/gt.2013.64
  • Dinculescu A, Min SH, Deng WT, Li Q and Hauswirth WW (2014) Gene therapy in the rd6 mouse model of retinal degeneration. Adv Exp Med Biol 801:711-8. doi: 10.1007/978-1-4614-3209-8_89
  • Han J, Dinculescu A, Dai X, Du W, Smith WC and Pang J (2013) Review: the history and role of naturally occurring mouse models with Pde6b mutations. Mol Vis 19:2579-89.
  • Deng WT, Sakurai K, Kolandaivelu S, Kolesnikov AV, Dinculescu A, Li J, Zhu P, Liu X, Pang J, Chiodo VA, Boye SL, Chang B, Ramamurthy V, Kefalov VJ and Hauswirth WW (2013) Cone phosphodiesterase-6alpha’ restores rod function and confers distinct physiological properties in the rod phosphodiesterase-6beta-deficient rd10 mouse. J Neurosci 33:11745-53. doi: 10.1523/JNEUROSCI.1536-13.2013
  • Pang JJ, Lei L, Dai X, Shi W, Liu X, Dinculescu A and McDowell JH (2012) AAV-mediated gene therapy in mouse models of recessive retinal degeneration. Curr Mol Med 12:316-30.
  • Dinculescu A, Estreicher J, Zenteno JC, Aleman TS, Schwartz SB, Huang WC, Roman AJ, Sumaroka A, Li Q, Deng WT, Min SH, Chiodo VA, Neeley A, Liu X, Shu X, Matias-Florentino M, Buentello-Volante B, Boye SL, Cideciyan AV, Hauswirth WW and Jacobson SG (2012) Gene therapy for retinitis pigmentosa caused by MFRP mutations: human phenotype and preliminary proof of concept. Hum Gene Ther 23:367-76. doi: 10.1089/hum.2011.169
  • Deng WT, Dinculescu A, Li Q, Boye SL, Li J, Gorbatyuk MS, Pang J, Chiodo VA, Matthes MT, Yasumura D, Liu L, Alkuraya FS, Zhang K, Vollrath D, LaVail MM and Hauswirth WW (2012) Tyrosine-mutant AAV8 delivery of human MERTK provides long-term retinal preservation in RCS rats. Invest Ophthalmol Vis Sci 53:1895-904. doi: 10.1167/iovs.11-8831
  • Vastinsalo H, Jalkanen R, Dinculescu A, Isosomppi J, Geller S, Flannery JG, Hauswirth WW and Sankila EM (2011) Alternative splice variants of the USH3A gene Clarin 1 (CLRN1). Eur J Hum Genet 19:30-5. doi: 10.1038/ejhg.2010.140
  • Ryals RC, Boye SL, Dinculescu A, Hauswirth WW and Boye SE (2011) Quantifying transduction efficiencies of unmodified and tyrosine capsid mutant AAV vectors in vitro using two ocular cell lines. Mol Vis 17:1090-102.
  • Petrs-Silva H*, Dinculescu A*, Li Q, Deng WT, Pang JJ, Min SH, Chiodo V, Neeley AW, Govindasamy L, Bennett A, Agbandje-McKenna M, Zhong L, Li B, Jayandharan GR, Srivastava A, Lewin AS and Hauswirth WW (2011) Novel properties of tyrosine-mutant AAV2 vectors in the mouse retina. Mol Ther 19:293-301. doi: 10.1038/mt.2010.234 (*, co-first authors)
  • Pang JJ, Dai X, Boye SE, Barone I, Boye SL, Mao S, Everhart D, Dinculescu A, Liu L, Umino Y, Lei B, Chang B, Barlow R, Strettoi E and Hauswirth WW (2011) Long-term retinal function and structure rescue using capsid mutant AAV8 vector in the rd10 mouse, a model of recessive retinitis pigmentosa. Mol Ther 19:234-42. doi: 10.1038/mt.2010.273
  • Tian G, Zhou Y, Hajkova D, Miyagi M, Dinculescu A, Hauswirth WW, Palczewski K, Geng R, Alagramam KN, Isosomppi J, Sankila EM, Flannery JG and Imanishi Y (2009) Clarin-1, encoded by the Usher Syndrome III causative gene, forms a membranous microdomain: possible role of clarin-1 in organizing the actin cytoskeleton. J Biol Chem 284:18980-93. doi: 10.1074/jbc.M109.003160
  • Petrs-Silva H, Dinculescu A, Li Q, Min SH, Chiodo V, Pang JJ, Zhong L, Zolotukhin S, Srivastava A, Lewin AS and Hauswirth WW (2009) High-efficiency transduction of the mouse retina by tyrosine-mutant AAV serotype vectors. Mol Ther 17:463-71. doi: 10.1038/mt.2008.269
  • Deng WT, Sakurai K, Liu J, Dinculescu A, Li J, Pang J, Min SH, Chiodo VA, Boye SL, Chang B, Kefalov VJ and Hauswirth WW (2009) Functional interchangeability of rod and cone transducin alpha-subunits. Proc Natl Acad Sci U S A 106:17681-6. doi: 10.1073/pnas.0901382106
  • Pang JJ, Boye SL, Kumar A, Dinculescu A, Deng W, Li J, Li Q, Rani A, Foster TC, Chang B, Hawes NL, Boatright JH and Hauswirth WW (2008) AAV-mediated gene therapy for retinal degeneration in the rd10 mouse containing a recessive PDEbeta mutation. Invest Ophthalmol Vis Sci 49:4278-83. doi: 10.1167/iovs.07-1622
  • Li Q, Miller R, Han PY, Pang J, Dinculescu A, Chiodo V and Hauswirth WW (2008) Intraocular route of AAV2 vector administration defines humoral immune response and therapeutic potential. Mol Vis 14:1760-9.
  • Li Q, Dinculescu A, Shan Z, Miller R, Pang J, Lewin AS, Raizada MK and Hauswirth WW (2008) Downregulation of p22phox in retinal pigment epithelial cells inhibits choroidal neovascularization in mice. Mol Ther 16:1688-94. doi: 10.1038/mt.2008.164
  • Aarnisalo AA, Pietola L, Joensuu J, Isosomppi J, Aarnisalo P, Dinculescu A, Lewin AS, Flannery J, Hauswirth WW, Sankila EM and Jero J (2007) Anti-clarin-1 AAV-delivered ribozyme induced apoptosis in the mouse cochlea. Hear Res 230:9-16. doi: 10.1016/j.heares.2007.03.004
  • Smith WC, Peterson JJ, Orisme W and Dinculescu A (2006) Arrestin translocation in rod photoreceptors. Adv Exp Med Biol 572:455-64. doi: 10.1007/0-387-32442-9_63
  • Molday LL, Min SH, Seeliger MW, Wu WW, Dinculescu A, Timmers AM, Janssen A, Tonagel F, Hudl K, Weber BH, Hauswirth WW and Molday RS (2006) Disease mechanisms and gene therapy in a mouse model for X-linked retinoschisis. Adv Exp Med Biol 572:283-9. doi: 10.1007/0-387-32442-9_39
  • Min SH, Molday LL, Seeliger MW, Dinculescu A, Timmers AM, Janssen A, Tonagel F, Tanimoto N, Weber BH, Molday RS and Hauswirth WW (2005) Prolonged recovery of retinal structure/function after gene therapy in an Rs1h-deficient mouse model of x-linked juvenile retinoschisis. Mol Ther 12:644-51. doi: 10.1016/j.ymthe.2005.06.002
  • Dinculescu A, Glushakova L, Min SH and Hauswirth WW (2005) Adeno-associated virus-vectored gene therapy for retinal disease. Hum Gene Ther 16:649-63. doi: 10.1089/hum.2005.16.649
  • Deng WT, Yan Z, Dinculescu A, Pang J, Teusner JT, Cortez NG, Berns KI and Hauswirth WW (2005) Adeno-associated virus-mediated expression of vascular endothelial growth factor peptides inhibits retinal neovascularization in a mouse model of oxygen-induced retinopathy. Hum Gene Ther 16:1247-54. doi: 10.1089/hum.2005.16.1247
  • Smith WC, Dinculescu A, Peterson JJ and McDowell JH (2004) The surface of visual arrestin that binds to rhodopsin. Mol Vis 10:392-8.
  • Dinculescu A, McDowell JH, Amici SA, Dugger DR, Richards N, Hargrave PA and Smith WC (2002) Insertional mutagenesis and immunochemical analysis of visual arrestin interaction with rhodopsin. J Biol Chem 277:11703-8. doi: 10.1074/jbc.M111833200

Book Chapters

  • “AAV Vectors for Retinal Gene Therapy” Seok-Hong Min, Astra Dinculescu, Lyudmyla G. Glushakova and William W. Hauswirth in book :“Parvoviruses”, Hodder Publishing Group, UK, 2005
  • “NADPH oxidase in choroidal neovascularization”, Qiuhong Li, Amrisha Verma, Astra Dinculescu, Alfred S. Lewin and William W. Hauswirth. In book: “Studies on Retinal and Choroidal Disorders”, Humana Press, 2012