The Dinculescu Lab

Photo Astra Dinculescu PhD

Principal Investigator

Astra Dinculescu, PhD
Assistant Professor

Contact Information

(352) 273-7548

astra@ufl.edu

Office:  Academic Research Building, Room R4-226

Lab:  Academic Research Building, Room R1-236

 

About the PI

Dr. Dinculescu received her PhD in Biochemistry from University of Florida in 2002. Her main research focus is on developing therapeutic approaches for Usher syndrome type 3, 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 retinal pigment epithelium (RPE)/Bruch’s membrane interface, and the mechanisms underlying 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 is intracellularly misrouted and gives rise to thick, widespread basal laminar deposits, similar histologically to those found in patients with late-onset retinal degeneration. She is currently exploring the molecular basis of this phenomenon, and testing the impact of other pathogenic C1QTNF5 mutations on RPE and photoreceptor cells.

Lab Staff

Lei Xu, Ph.D. Postdoctoral Fellow
Susan Bolch, Ph.D. Biological Research scientist
James Hugh McDowell, Ph.D. Scientist Emeritus
Chiab Simpson, Research Technician

Areas of Interest:

  • inherited retinal diseases
  • Usher syndrome
  • Age-related macular degeneration (AMD)
  • recombinant AAV-mediated gene therapy
  • protein aggregation
  • retinal pigment epithelium
  • extracellular matrix remodeling

Grants

R01 EY026559-01A1, Astra Dinculescu (PI) 09/01/2016-08/31/2021
“Clarin-1 retinal function and therapeutic implications for USH3”

M2017035 BrightFocus Foundation Award, Astra Dinculescu (PI) 06/01/2017-05/01/2019
“The role of basal C1QTNF5-S163R mutant deposits in drusen formation:  implications for Age Related Macular Degeneration”

Publications

Dinculescu A, Dyka FM, Min SH, Stupay RM, Hooper MJ, Smith WC, Hauswirth WW. Co-Expression of Wild-Type and Mutant S163R C1QTNF5 in Retinal Pigment Epithelium. Adv Exp Med Biol. 2018;1074:61-6. doi: 10.1007/978-3-319-75402-4_8. PubMed PMID: 29721928.

Deng WT, Kolandaivelu S, Dinculescu A, Li J, Zhu P, Chiodo VA, Ramamurthy V, Hauswirth WW. Cone Phosphodiesterase-6gamma’ Subunit Augments Cone PDE6 Holoenzyme Assembly and Stability in a Mouse Model Lacking Both Rod and Cone PDE6 Catalytic Subunits. Front Mol Neurosci. 2018;11:233. doi: 10.3389/fnmol.2018.00233. PubMed PMID: 30038560; PMCID: PMC6046437.

Chekuri A, Sahu B, Chavali VRM, Voronchikhina M, Hermida AS, Suk JJ, Alapati AN, Bartsch DU, Ayala-Ramirez R, Zenteno JC, Dinculescu A, Jablonski MM, Borooah S, Ayyagari R. The long-term effects of gene therapy in a novel mouse model of human MFRP-associated retinopathy. Hum Gene Ther. 2018. doi: 10.1089/hum.2018.192. PubMed PMID: 30499344.

Mowat FM, Occelli LM, Bartoe JT, Gervais KJ, Bruewer AR, Querubin J, Dinculescu A, Boye SL, Hauswirth WW, Petersen-Jones SM. Gene Therapy in a Large Animal Model of PDE6A-Retinitis Pigmentosa. Front Neurosci. 2017;11:342. doi: 10.3389/fnins.2017.00342. PubMed PMID: 28676737; PMCID: PMC5476745.

Geng R, Omar A, Gopal SR, Chen DH, Stepanyan R, Basch ML, Dinculescu A, Furness DN, Saperstein D, Hauswirth W, Lustig LR, Alagramam KN. Modeling and Preventing Progressive Hearing Loss in Usher Syndrome III. Sci Rep. 2017;7(1):13480. doi: 10.1038/s41598-017-13620-9. PubMed PMID: 29044151; PMCID: PMC5647385.

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, Hauswirth WW. AAV-Mediated Clarin-1 Expression in the Mouse Retina: Implications for USH3A Gene Therapy. PLoS One. 2016;11(2):e0148874. doi: 10.1371/journal.pone.0148874. PubMed PMID: 26881841; PMCID: PMC4755610.

Dinculescu A, Min SH, Dyka FM, Deng WT, Stupay RM, Chiodo V, Smith WC, Hauswirth WW. Pathological Effects of Mutant C1QTNF5 (S163R) Expression in Murine Retinal Pigment Epithelium. Invest Ophthalmol Vis Sci. 2015;56(11):6971-80. doi: 10.1167/iovs.15-17166. PubMed PMID: 26513502; PMCID: PMC4627469.

Deng WT, Dyka FM, Dinculescu A, Li J, Zhu P, Chiodo VA, Boye SL, Conlon TJ, Erger K, Cossette T, Hauswirth WW. Stability and Safety of an AAV Vector for Treating RPGR-ORF15 X-Linked Retinitis Pigmentosa. Hum Gene Ther. 2015;26(9):593-602. doi: 10.1089/hum.2015.035. PubMed PMID: 26076799; PMCID: PMC4575541.

Mowat FM, Gornik KR, Dinculescu A, Boye SL, Hauswirth WW, Petersen-Jones SM, Bartoe JT. Tyrosine capsid-mutant AAV vectors for gene delivery to the canine retina from a subretinal or intravitreal approach. Gene Ther. 2014;21(1):96-105. doi: 10.1038/gt.2013.64. PubMed PMID: 24225638; PMCID: PMC3880610.

Dinculescu A, Min SH, Deng WT, Li Q, Hauswirth WW. Gene therapy in the rd6 mouse model of retinal degeneration. Adv Exp Med Biol. 2014;801:711-8. doi: 10.1007/978-1-4614-3209-8_89. PubMed PMID: 24664762.

Han J, Dinculescu A, Dai X, Du W, Smith WC, Pang J. Review: the history and role of naturally occurring mouse models with Pde6b mutations. Mol Vis. 2013;19:2579-89. PubMed PMID: 24367157; PMCID: PMC3869645.

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, Hauswirth WW. Cone phosphodiesterase-6alpha’ restores rod function and confers distinct physiological properties in the rod phosphodiesterase-6beta-deficient rd10 mouse. J Neurosci. 2013;33(29):11745-53. doi: 10.1523/JNEUROSCI.1536-13.2013. PubMed PMID: 23864662; PMCID: PMC3713718.

To see a complete listing of publications, please click here.