Wen Tao Deng, PhD

Dr. Deng joined the Dept of Ophthalmology/Biochemistry at WVU in March 2021. Her research centers on developing gene therapy to treat inherited retina disease, and to study disease mechanism associated with retinal degeneration

Assistant Professor

Organization:

West Virginia University School of Medicine

Department:

Ophthalmology and Visual Sciences

Classification:

Faculty

Assistant Professor

Organization:

West Virginia University School of Medicine

Department:

Biochemistry and Molecular Medicine

Classification:

Adjunct Faculty

• PhD, University of FLorida, 2000

PUBLICATIONS IN JOURNALS

1.   Sechrest ER, Barbera RJ, Ma X, Dyka F, Ahn J, Brothers B, Cahill M, Hall I, Baehr W, Deng WT. Expression of red/green-cone opsin mutants K82E, P187S, M273K result in unique pathobiological perturbations to cone structure and function. Accepted in Frontiers in Neuroscience.  

2.    Sechrest ER, Ma X, Cahill ME, Barbera RJ, Wang Y, Deng WT. Structural and functional rescue of cones carrying the most common cone opsin C203R missense mutation. JCI Insight. 2024 Jan 23;9(2):e172834. doi: 10.1172/jci.insight.172834. PMID: 38060327.

3.    Sechrest ER, Chmelik K, Tan WD, Deng WT. Blue cone monochromacy and gene therapy. Vision Res. 2023 Jul;208:108221. doi: 10.1016/j.visres.2023.108221. Epub 2023 Mar 29. PMID: 37001420; PMCID: PMC10182257.

4.    Ma X, Sechrest E, Fajardo D, Zhu P, Dyka FM, Wang Y, Lobanova E, Boye S, Baehr W, Deng WT. Gene Therapy in Opn1mw-/-/Opn1sw-/- Mice and Implications for Blue Cone Monochromacy Patients with Deletion Mutations. Hum Gene Ther. 2022 Mar 10. doi: 10.1089/hum.2021.298. PMID: 35272502

5.    Zhu P, Dyka F, Ma X, Yin L, Yu H, Baehr W, Hauswirth WW, Deng WT. Disease mechanisms of X-linked cone dystrophy caused by missense mutations in the red and green cone opsins. FASEB J. 2021 Oct;35(10): e21927. doi: 10.1096/fj.202101066R. PMID: 34547123

6.    Deng WT, Li J, Zhu P, Freedman B, Smith WC, Baehr W, Hauswirth WW. Rescue of M-cone Function in Aged Opn1mw^-/- Mice, a Model for Late-Stage Blue Cone Monochromacy. Invest Ophthalmol Vis Sci. 2019 Aug 1;60(10):3644-3651

7.    Song C, Conlon TJ, Deng WT, Coleman KE, Zhu P, Plummer C, Mandapati S, Van Hoosear M, Green KB, Sonnentag P, Sharma AK, Timmers A, Robinson PM, Knop DR, Hauswirth WW, Chulay JD, Shearman MS, Ye GJ. Toxicology and Pharmacology of an AAV Vector Expressing Codon-Optimized RPGR in RPGR-Deficient Rd9 Mice. Hum Gene Ther Clin Dev. 2018 Dec;29(4):188-197

8.    Deng WT, Kolandaivelu S, Dinculescu A, Li J, Zhu P, Chiodo VA., Ramamurthy V, Hauswirth WW. Cone Phosphodiesterase-6γ' Subunit Augments Cone PDE6 Holoenzyme Assembly and Stability in a Mouse Model Lacking Both Rod and Cone PDE6 Catalytic Subunits. Front Mol Neurosci. 2018 Jul 9;11:233. 

9.    Deng WT, Jie Li, Ping Zhu, Vince A. Chiodo, Uwe Wolfrum, Wolfgang Baehr, W. Clay Smith, Jijing Pang, William W. Hauswirth. Human Opsins Restore M-Cone Function and structure in a Mouse Model for Human Blue Cone Monochromacy. Molecular Vision, 2018 Jan 24:17-28.

10.    Zhang Y, Deng WT (co-first author), Li J, Zhu P, Baehr W,  Pang JJ, Hauswirth WW. Gene-based Therapy in a Mouse Model of Blue Cone Monochromacy. Scientific Reports, 2017 Jul 27;7(1):6690.

11.    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 Feb 16;11(2):e0148874  

12.    Ghazi NG, Abboud EB, Nowilaty SR, Alkuraya H, Alhommadi A, Cai H, Hou R, Deng WT, Boye SL, Almaghamsi A, Al Saikhan F, Al-Dhibi H, Birch D, Chung C, Colak D, LaVail MM, Vollrath D, Erger K, Wang W, Conlon T, Zhang K, Hauswirth W, Alkuraya FS. Treatment of retinitis pigmentosa due to MERTK mutations by ocular subretinal injection of adeno-associated virus gene vector: results of a phase I trial. Hum Genet. 2016 Mar;135(3):327-43

13.  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 Oct; 56(11):6971-80.

14.  Beltran WA, Cideciyan AV, Iwabe S, Swider M, Kosyk MS, McDaid K, Martynyuk I, Ying GS, Shaffer J, Deng WT, Boye SL, Lewin AS, Hauswirth WW, Jacobson SG, Aguirre GD. Successful arrest of photoreceptor and vision loss expands the therapeutic window of retinal gene therapy to later stages of disease. Proc Natl Acad Sci U S A. 2015 Oct 27;112(43):E5844-53.

15.  LaVail MM, Yasumura D, Matthes MT, Yang H, Hauswirth WW, Deng WT, Vollrath D. Gene Therapy for MERTK-Associated Retinal Degenerations. Adv Exp Med Biol. 2016; 854:487-93.

16.  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 Sep; 26(9):593-602.

17.  Du W, Tao Y, Deng WT, Zhu P, Li J, Dai X, Zhang Y, Shi W, Liu X, Chiodo VA, Ding XQ, Zhao C, Michalakis S, Biel M, Zhang Z, Qu J, Hauswirth WW, Pang JJ. Vitreal delivery of AAV vectored Cnga3 restores cone function in CNGA3-/-/Nrl-/- mice, an all-cone model of CNGA3 achromatopsia. Hum Mol Genet. 2015 Jul 1;24(13):3699-707.

18.  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.

19.  Dai X, Han J, Qi Y, Zhang H, Xiang L, Lv J, Li J, Deng WT, Chang B, Hauswirth WW, and  Pang JJ. AAV-Mediated Lysophosphatidylcholine Acyltransferase 1 (Lpcat1) Gene Replacement Therapy Rescues Retinal Degeneration in rd11 Mice.  Invest Ophthalmol Vis Sci.  2014, 55(3): 1724-34.   

20.  Deng WT, Sakurai K, Kolandaivelu S, Kolesnikov AV, Dinculescu A, Li J, Zhu P, Liu X, Pang J, Chiodo VA, Boye SL, Chang Bo, Ramamurthy V, Kefalov VJ,  Hauswirth W.  Cone Phosphodiesterase-6α’ Restores Rod Function and Confers Distinct Physiological Properties in the Rod Phosphodiesterase-6β Deficient rd10 Mouse. Journal of Neuroscience.  2013, 33(29): 11745-53. 

21.  Conlon TJ, Deng WT (co-first author), Erger K, Cossette T, Pang JJ, Ryals R, Clément N, Cleaver B, McDoom I, Boye SE, Peden MC, Sherwood MB, Abernathy CR, Alkuraya FS, Boye SL, Hauswirth WW. Preclinical Potency and Safety Studies of an AAV2-Mediated Gene Therapy Vector for the Treatment of MERTK Associated Retinitis Pigmentosa. Hum Gene Ther Clin Dev. 2013, 24(1):23-8.

22.  Pang JJ, Deng WT (co-first author), Dai X, Lei B, Everhart D, Umino Y, Li J, Zhang K, Mao S, Boye SL, Liu L, Chiodo VA, Liu X, Shi W, Tao Y, Chang B, Hauswirth WW. AAV-mediated cone rescue in a naturally occurring mouse model of CNGA3-achromatopsia. PLoS One. 2012, 7(4): e35250

23.  Deng WT, Dinculescu A, Li Q, Boye SL, Li J, Gorbatyuk MS, Pang J, Chiodo V, Liu L, Alkuraya F, Zhang K, Vollrath D, LaVail MM,  HauswirthWW. Tyrosine-mutant AAV8 delivery of human MERTK provides long-term retinal preservation in RCS Rats. Invest Ophthalmol Vis Sci. 2012, 53(4):1895-904.

24.  Beltran WA, Cideciyan AV, Lewin AS, Iwabe S, Khanna H, Sumaroka A, Chiodo VA, Fajardo DS, Román AJ, Deng WT, Swider M, Alemán TS, Boye SL, Genini S, Swaroop A, Hauswirth WW, Jacobson SG, Aguirre GD. Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa. Proc Natl Acad Sci U S A. 2012, 109(6):2132-7.

25.  Dinculescu A, Estreicher J, Zenteno JC, Aleman TS, Schwartz SB, Huang WC, Roman AJ, Sumaroka A, Deng WT, Min SH, Chiodo V, Neeley AW, Liu X, Shu X, Matias-Florentino M, Buentello-Volante B, Boye SL, Cideciyan AV, Hauswirth WW, Jacobson SG. Gene therapy for retinitis pigmentosa caused by MFRP mutations: human phenotype and preliminary proof of concept.  Hum Gene Ther. 2012, 23(4):367-76.

26.  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, Hauswirth WW.  Novel properties of tyrosine-mutant AAV2 vectors in the mouse retina. Molecular Therapy. 2011, 19(2):293-301.

27.  Lobanova ES, Herrmann R, Finkelstein S, Reidel B, Skiba NP, Deng WT, Jo R, Weiss ER, Hauswirth WW, Arshavsky VY.  Mechanistic basis for the failure of cone transducin to translocate: why cones are never blinded by light.  J Neuroscience. 2010, 30(20):6815-24.  

28.  Deng WT, Sakurai K, Liu J, Dinculescu A, Li J, Pang J, Min SH, Chiodo VA, Boye SL, Chang B, Kefalov VJ, Hauswirth WW. Functional interchangeability of rod and cone transducin alpha-subunits. Proc Natl Acad Sci USA, 2009, 106 (42):17681-6.

29.  Pang JJ, Boye SL, Kumar A, Dinculescu A, Deng W, Li J, Li Q, Rani A, Foster TC, Chang B, Hawes NL, Boatright JH, Hauswirth WW. AAV-mediated gene therapy for retinal degeneration in the rd10 mouse containing a recessive PDEbeta mutation. Invest Ophthalmol Vis Sci. 2008, 49(10):4278-83.

30.  Pang JJ, Lauramore A, Deng WT, Li Q, Doyle TJ, Chiodo V, Li J, Hauswirth WW. Comparative analysis of in vivo and in vitro AAV vector transduction in the neonatal mouse retina: effects of serotype and site of administration. Vision Research, 2008, 48(3):377-85.

31.  Lutty GA, Chan-Ling T, Phelps DL, Adamis AP, Berns KI, Chan CK, Cole CH, D’Amore PA, Das A, Deng WT, Dobson V, Flynn JT, Friedlander M, Fulton A, Good WV, Grant MB, Hansen R, Hauswirth WW, Hardy RJ, Hinton DR, Hughes S, McLeod DS, Palmer EA, Patz A, Penn JS, Raisler BJ, Repka MX, Saint-Geniez M, Shaw LC, Shima DT, Smith BT, Smith LE, Tahija SG, Tasman W, Trese MT. Proceedings of the Third International Symposium on Retinopathy of Prematurity: an update on ROP from the lab to the nursery (November 2003, Anaheim, California). Molecular Vision. 2006,12: 532-80.

32.  Deng WT, Yan Z, Dinculescu A, Pang J, Teusner JT, Cortez NG, Berns KI, Hauswirth WW. Adeno-associated virus-mediated expression of vascular endothelial growth factor peptides inhibits retinal neovascularization in a mouse model of oxygen-induced retinopathy. Human Gene Therapy. 2005, 16(11):1247-54.

33.  Tan BC, Joseph LM, Deng WT (co-first author), Liu L, Li QB, Cline K, McCarty DR. Molecular characterization of the Arabidopsis 9-cis epoxycarotenoid dioxygenase gene family. Plant J. 2003, 35(1):44-56.

 

BOOK CHAPTERS

1. 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.
2. Pang JJ, Alexander J, Lei B, Deng W, Zhang K, Li Q, Chang B, Hauswirth WW. Achromatopsia as a potential candidate for gene therapy. Adv Exp Med Biol. 2010, 664:639-46.
3.  Raisler BJ, Deng WT, Hauswirth WW. Adeno-associated virus mediated gene therapy for vascular retinopathies. Laboratory Techniques in Biochemistry and Molecular Biology.2005. Vol 31.

 

Dr. Deng’s long-term research goals are to uncover molecular mechanisms underlying cone photoreceptor death in diseases associated with cone- and cone-rod dystrophies, and to develop therapeutic strategies to prevent cone death in these conditions. Her core project focuses on characterizing disease mechanisms and developing therapies for congenital diseases resulting from cone opsin mutations. Currently she is developing gene therapy for treating blue cone monochromacy, an X-linked congenital disorder with severe cone dysfunction due to loss of both L- and M- cone function.

Ophthalmology

*Currently accepting undergraduate researchers, graduate students, and recruiting post-doctoral fellows for this summer and fall of 2024.

Description of Research

AAV-mediated gene therapy for cone dystrophy caused by cone opsin mutations.

In the human retina, L (long-wavelength)- and M (middle-wavelength)- cones constitute about 95% of the total cone population and are primarily concentrated in the central macula responsible for our daylight, color, and fine spatial vision. X-linked retinal diseases resulting from mutations in the L- and M- opsin genes are associated with a wide range of visual defects including red/green color vision deficiency, blue cone monochromacy, X-linked cone dystrophy/dysfunction, and high myopia with abnormal cone function.

Our recent work centers on gene therapy on blue cone monochromacy (BCM), an X-linked congenital vision disorder characterized by complete loss or severely reduced L- and M-cone function. Patients with BCM display poor visual acuity, severely impaired color discrimination, myopia, nystagmus, and minimally detectable cone-mediated function.  We showed that adeno-associated vector (AAV)-mediated gene replacement therapy rescued cone function and structure in animal models resembling patients carrying cone opsin deletion mutations.

     

Moreover, our recent work also showed that most cone opsin point mutations may display a dominant phenotype, and a different approach may be needed to treat this “gain-of-function” cone dystrophy/dysfunction. We plan to use AAV-shRNA to knockdown the mutant mRNA expression, at the same time supplement a shRNA resistant cDNA for therapy. We will also use AAV-CRISPR/Cas9-based gene editing tool to either destroy the mutation + supplement, as well as try allele-targeted correction.

To investigate cellular mechanisms leading to cone death in different classes of cone opsin mutants. 

We will use RNAseq, metabolomics studies to identify signature molecules and pathways causing cone photoreceptor degeneration in animal models carrying different categories of cone opsin mutations. This information will help us to develop pharmacological compounds that may prolong cone survival.  

To investigate disease mechanisms associated with other mutations causing cone dystrophy/dysfunction.

Currently, studies on degenerative diseases of the retina have been mostly centered on rod photoreceptors, comparable studies on disease mechanisms of cone degeneration resulting from cone dystrophy, cone-rod dystrophy have been lagging. Genetic causes are known in about half of these conditions and these genes perform a diverse range of functions including phototransduction, outer segment morphogenesis, intraflagellar transport, and neurotransmitter release. Our long-term goal is to investigate disease mechanisms associated with these mutations and to develop therapy. We will also use the knowledge obtained to explore age-related macular degeneration, a complex multifactorial disease that mainly affects cones in the macular region.