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Prof Robin Ali
Telephone:020 7608 6817
Fax:020 7608 6991
Address:UCL Institute of Ophthalmology,
11-43 Bath Street,
Appointments:Professor of Human Molecular Genetics, Inst Ophthalmology - Genetics, Institute of Ophthalmology
The main focus of my research is the development of gene and stem cell therapy with the primary aim of developing novel treatments for eye disease. Over the past ten years we have been optimising gene transfer to the eye. We are engaged in a comprehensive programme of work to develop gene therapy for eye disease and in particular for disorders affecting the retina, including inherited retinal degeneration as well as complex diseases such as those associated with retinal and choroidal neovascularisation and posterior uveitis.
My research has utilised a variety of viral vectors, but my main interest is in the development of vector systems based on either adeno-associated virus (AAV) or lentiviruses. We have demonstrated the utility of these systems for gene transfer to the eye. A major aspect of our research is the development and use of a wide variety of genetic and experimental animal models of retinal disorders, including large animal models, in order to assess novel therapeutic approaches. We are engaged in a broad programme of work to demonstrate proof of concept for a number of alternative strategies, including gene replacement therapy and/or delivery of siRNA to treat animal models of inherited retinal degeneration and delivery of genes encoding angiostatic, anti-apoptotic, immunomodulatory or neurotrophic molecules to treat a variety of animal models. We are now also investigating the potential of stem or progenitor cell transplantation to repair degenerating retinae. A recent key discovery is that transplantation of rod precursor cells at a specific stage of development results in their integration and subsequent differentiation into rod photoreceptors that form synaptic connections and improve visual function in mouse models of retinal degeneration. Conversely, transplantation of progenitor or stem cells that are not at this precise ontogentic stage do not show this property and fail to integrate. We are now combining gene therapy approaches with that of stem cell transplantation and using viral vectors carrying genes encoding a variety of transcription factors in order to generate appropriate cells for transplantation from either embryonic or adult-derived stem cells.
In order to deliver new treatments, we have now established a programme of translational research. My research group includes a number of clinicians (clinical training fellows as well as senior clinican/scientists) and we have strong links with a number of biotechnology companies. We have recently established a Department of Health funded clinical trial of gene therapy for a form of severe childhood-onset retinal dystrophy due to mutations in the gene encoding RPE65. This condition is likely to be particularly amenable to effective treatment and the trial should facilitate future trials and underpin the programme of development of treatments for other retinal disorders. The first patients were enrolled in early 2007 and the first results from the trial were published in the New England Journal of Medicine in May 2008.
- Development of novel therapies for the treatment of retinal degeneration
- Differentiation of polarised epithelia
- Inherited Eye Disease
Displaying 50 most recent publications. For the full list please visit UCL Discovery
- Gonzalez-Cordero A,West EL,Pearson RA,Duran Y,Carvalho LS,Chu CJ,Naeem A,Blackford SJ,Georgiadis A,Lakowski J,Hubank M,Smith AJ,Bainbridge JW,Sowden JC,Ali RR (2013) Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina. Nat Biotechnol. 10.1038/nbt.2643.
- Chu CJ,Herrmann P,Carvalho LS,Liyanage SE,Bainbridge JW,Ali RR,Dick AD,Luhmann UF (2013) Assessment and in vivo scoring of murine experimental autoimmune uveoretinitis using optical coherence tomography. PLoS One, 8(5), e63002. 10.1371/journal.pone.0063002.
- Mowat FM,Breuwer AR,Bartoe JT,Annear MJ,Zhang Z,Smith AJ,Bainbridge JW,Petersen-Jones SM,Ali RR (2013) RPE65 gene therapy slows cone loss in Rpe65-deficient dogs. Gene Ther, 20(5), 545 - 555. 10.1038/gt.2012.63.
- Luhmann UF,Carvalho LS,Robbie SJ,Cowing JA,Duran Y,Munro PM,Bainbridge JW,Ali RR (2013) Ccl2, Cx3cr1 and Ccl2/Cx3cr1 chemokine deficiencies are not sufficient to cause age-related retinal degeneration. Exp Eye Res, 107, 80 - 87. 10.1016/j.exer.2012.11.015.
- Boucherie C,Mukherjee S,Henckaerts E,Thrasher AJ,Sowden JC,Ali RR (2013) Brief report: self-organizing neuroepithelium from human pluripotent stem cells facilitates derivation of photoreceptors. Stem Cells, 31(2), 408 - 414. 10.1002/stem.1268.
- Luhmann UF,Carvalho LS,Robbie SJ,Bainbridge JW,Ali RR (2013) Reply to comment on "Ccl2, Cx3cr1 and Ccl2/Cx3cr1 chemokine deficiencies are not sufficient to cause age-related retinal degeneration" by Luhmann et al. (Exp. Eye Res. 107, February 2013, 80-87). Exp Eye Res, 111, 136. 10.1016/j.exer.2013.02.001.
- Petsoglou C,Balaggan KS,Dart JKG,Bunce C,Xing W,Ali RR,Tuft SJ (2012) Subconjunctival bevacizumab induces regression of corneal neovascularisation: A pilot randomised placebo-controlled double-masked trial British Journal of Ophthalmology.
- Kampik D,Ali RR,Larkin DF (2012) Experimental gene transfer to the corneal endothelium. Exp Eye Res, 95(1), 54 - 59. 10.1016/j.exer.2011.07.001.
- Sundaram V,Wilde C,Webster AR,Moore AT,Nardini M,Ali RR,Bainbridge JW,Carroll J,Michaelides M (2012) Cone Photoreceptor Structure in Achromatopsia Investigative Ophthalmology and Visual Science, 53, E-Abstract 2678.
- Lange CA,Luhmann UF,Mowat FM,Georgiadis A,West EL,Abrahams S,Sayed H,Powner MB,Fruttiger M,Smith AJ,Sowden JC,Maxwell PH,Ali RR,Bainbridge JW (2012) Von Hippel-Lindau protein in the RPE is essential for normal ocular growth and vascular development. Development, 139(13), 2340 - 2350. 10.1242/dev.070813.
- West EL,Gonzalez-Cordero A,Hippert C,Osakada F,Martinez-Barbera JP,Pearson RA,Sowden JC,Takahashi M,Ali RR (2012) Defining the integration capacity of embryonic stem cell-derived photoreceptor precursors. Stem Cells, 30(7), 1424 - 1435. 10.1002/stem.1123.
- Luhmann UF,Lange CA,Robbie S,Munro PM,Cowing JA,Armer HE,Luong V,Carvalho LS,MacLaren RE,Fitzke FW,Bainbridge JW,Ali RR (2012) Differential modulation of retinal degeneration by Ccl2 and Cx3cr1 chemokine signalling. PLoS One, 7(4), e35551. 10.1371/journal.pone.0035551.
- Pearson RA,Barber AC,Rizzi M,Hippert C,Xue T,West EL,Duran Y,Smith AJ,Chuang JZ,Azam SA,Luhmann UF,Benucci A,Sung CH,Bainbridge JW,Carandini M,Yau KW,Sowden JC,Ali RR (2012) Restoration of vision after transplantation of photoreceptors. Nature, 485(7396), 99 - 103. 10.1038/nature10997.
- Ali RR (2012) Gene therapy for retinal dystrophies: twenty years in the making. Hum Gene Ther, 23(4), 337 - 339. 10.1089/hum.2012.2506.
- Tan MH,Mackay DS,Cowing J,Tran HV,Smith AJ,Wright GA,Dev-Borman A,Henderson RH,Moradi P,Russell-Eggitt I,MacLaren RE,Robson AG,Cheetham ME,Thompson DA,Webster AR,Michaelides M,Ali RR,Moore AT (2012) Leber congenital amaurosis associated with AIPL1: challenges in ascribing disease causation, clinical findings, and implications for gene therapy. PLoS One, 7(3), e32330. 10.1371/journal.pone.0032330.
- Mowat FM,Gonzalez F,Luhmann UF,Lange CA,Duran Y,Smith AJ,Maxwell PH,Ali RR,Bainbridge JW (2012) Endogenous erythropoietin protects neuroretinal function in ischemic retinopathy. Am J Pathol, 180(4), 1726 - 1739. 10.1016/j.ajpath.2011.12.033.
- Ali RR (2012) Ocular gene therapy: introduction to the special issue. Gene Ther, 19(2), 119 - 120. 10.1038/gt.2011.189.
- Luhmann UF,Ali RR (2012) Local vs. systemic mononuclear phagocytes in age-related macular degeneration and their regulation by CCL2-CCR2 and CX3CL1-CX3CR1 chemokine signalling. Adv Exp Med Biol, 723, 17 - 22. 10.1007/978-1-4614-0631-0_3.
- Sundaram V,Moore AT,Ali RR,Bainbridge JW (2012) Retinal dystrophies and gene therapy. Eur J Pediatr, 171(5), 757 - 765. 10.1007/s00431-011-1615-2.
- Smith AJ,Bainbridge JW,Ali RR (2012) Gene supplementation therapy for recessive forms of inherited retinal dystrophies. Gene Ther, 19(2), 154 - 161. 10.1038/gt.2011.161.
- West EL,Pearson RA,Duran Y,Gonzalez-Cordero A,MacLaren RE,Smith AJ,Sowden JC,Ali RR (2012) Manipulation of the recipient retinal environment by ectopic expression of neurotrophic growth factors can improve transplanted photoreceptor integration and survival. Cell Transplant, 21(5), 871 - 887. 10.3727/096368911X623871.
- West EL,Gonzalez-Cordero A,Hippert C,Duran Y,Pearson RA,Sowden JC,Ali RR (2011) Embryonic stem cell-derived retinal cells transplanted to the adult retina HUM GENE THER, 22(10), A79 - A80.
- Decembrini S,Cananzi M,Gualdoni S,Battersby A,Allen N,Pearson RA,Ali RR,De Coppi P,Sowden JC (2011) Comparative analysis of the retinal potential of embryonic stem cells and amniotic fluid-derived stem cells. Stem Cells Dev, 20(5), 851 - 863. 10.1089/scd.2010.0291.
- Hippert C,Barber AC,Georgiadis A,Smith AJ,Swoden JC,Ali RR,Pearson RA (2011) Using shGFAP to examine the impact of gliosis on photoreceptor transplantation efficacy HUM GENE THER, 22(10), A41 - A41.
- Carvalho LS,Mihelec M,Pearson RA,Bainbridge JWB,Smith AJ,Ali RR (2011) Gene replacement therapy in mouse models of inherited cone photoreceptor disorders HUM GENE THER, 22(10), A25 - A25.
- Ali RR (2011) Development of stem cell therapy for the treatment of retinal degeneration HUM GENE THER, 22(10), A10 - A11.
- Gualdoni S,Baron M,Lakowski J,Decembrini S,Pearson RA,Ali RR,Sowden JC (2011) Isolation and culture of adult ciliary epithelial cells, previously identified as retinal stem cells, and retinal progenitor cells. Curr Protoc Stem Cell Biol, Chapter 1, Unit - 1H.4. 10.1002/9780470151808.sc01h04s19.
- Lakowski J,Han YT,Pearson RA,Gonzalez-Cordero A,West EL,Gualdoni S,Barber AC,Hubank M,Ali RR,Sowden JC (2011) Effective transplantation of photoreceptor precursor cells selected via cell surface antigen expression. Stem Cells, 29(9), 1391 - 1404. 10.1002/stem.694.
- Boucherie C,Sowden JC,Ali RR (2011) Induced pluripotent stem cell technology for generating photoreceptors. Regen Med, 6(4), 469 - 479. 10.2217/rme.11.37.
- Lange CA,Stavrakas P,Luhmann UF,de Silva DJ,Ali RR,Gregor ZJ,Bainbridge JW (2011) Intraocular oxygen distribution in advanced proliferative diabetic retinopathy. Am J Ophthalmol, 152(3), 406 - 412.e3. 10.1016/j.ajo.2011.02.014.
- Mihelec M,Pearson RA,Robbie SJ,Buch PK,Azam SA,Bainbridge JW,Smith AJ,Ali RR (2011) Long-term preservation of cones and improvement in visual function following gene therapy in a mouse model of leber congenital amaurosis caused by guanylate cyclase-1 deficiency. Hum Gene Ther, 22(10), 1179 - 1190. 10.1089/hum.2011.069.
- Carvalho LS,Xu J,Pearson RA,Smith AJ,Bainbridge JW,Morris LM,Fliesler SJ,Ding XQ,Ali RR (2011) Long-term and age-dependent restoration of visual function in a mouse model of CNGB3-associated achromatopsia following gene therapy. Hum Mol Genet, 20(16), 3161 - 3175. 10.1093/hmg/ddr218.
- Bartholomae CC,Arens A,Balaggan KS,Yáñez-Muñoz RJ,Montini E,Howe SJ,Paruzynski A,Korn B,Appelt JU,Macneil A,Cesana D,Abel U,Glimm H,Naldini L,Ali RR,Thrasher AJ,von Kalle C,Schmidt M (2011) Lentiviral vector integration profiles differ in rodent postmitotic tissues. Mol Ther, 19(4), 703 - 710. 10.1038/mt.2011.19.
- Ali RR,Sowden JC (2011) Regenerative medicine: DIY eye. Nature, 472(7341), 42 - 43. 10.1038/472042a.
- Buch PK,Mihelec M,Cottrill P,Wilkie SE,Pearson RA,Duran Y,West EL,Michaelides M,Ali RR,Hunt DM (2011) Dominant cone-rod dystrophy: a mouse model generated by gene targeting of the GCAP1/Guca1a gene. PLoS One, 6(3), e18089. 10.1371/journal.pone.0018089.
- Annear MJ,Bartoe JT,Barker SE,Smith AJ,Curran PG,Bainbridge JW,Ali RR,Petersen-Jones SM (2011) Gene therapy in the second eye of RPE65-deficient dogs improves retinal function GENE THER, 18(1), 53 - 61. 10.1038/gt.2010.111.
- Luhmann UFO,Kampik D,Basche M,Smith AJ,Larkin DFP,Ali RR (2011) Replication of retinal pigment epithelium can be induced by non integrating lentiviral gene transfer of E2F2 HUM GENE THER, 22(10), A78 - A78.
- Ali RR,Bainbridge JW,Smith AJ,Robbie S,Fitzke FW,Holder GE,Stockman A,Yzer Z,Van den Born I,Rubin GS (2010) Clinical trial of gene therapy for early onset severe retinal dystrophy resulting from defects in RPE65 HUMAN GENE THERAPY, 21(10), 1393 - 1393.
- Georgiadis A,Tschernutter M,Bainbridge JW,Robbie SJ,McIntosh J,Nathwani AC,Smith AJ,Ali RR (2010) AAV-mediated knockdown of peripherin-2 in vivo using miRNA-based hairpins. Gene Ther, 17(4), 486 - 493. 10.1038/gt.2009.162.
- Kampik D,Smith A,Luhmann UFO,Buch P,Larkin DFP,Ali RR (2010) Non-Integrating Lentiviral Gene Transfer of E2F2 to Induce Corneal Endothelial Cell Replication HUMAN GENE THERAPY, 21(9), 1200 - 1200.
- Ali RR,Bainbridge JWB,Smith AJ,Fitzke FW,Holder GE,Stockman A,Bhattacharya SS,Rubin GS,Yzer S,van den Born I,Moore AT (2010) Clinical Trial of Gene Therapy for Early Onset Severe Retinal Dystrophy Resulting from Defects in RPE65 HUMAN GENE THERAPY, 21(9), 1174 - 1175.
- Lakowski J,Baron M,Bainbridge J,Barber AC,Pearson RA,Ali RR,Sowden JC (2010) Cone and rod photoreceptor transplantation in models of the childhood retinopathy Leber congenital amaurosis using flow-sorted Crx-positive donor cells Hum.Mol.Genet, 19, 4545 - 4559.
- West EL,Pearson RA,Barker SE,Luhmann UF,Maclaren RE,Barber AC,Duran Y,Smith AJ,Sowden JC,Ali RR (2010) Long-term survival of photoreceptors transplanted into the adult murine neural retina requires immune modulation. Stem Cells, 28(11), 1997 - 2007. 10.1002/stem.520.
- Aartsen WM,van Cleef KW,Pellissier LP,Hoek RM,Vos RM,Blits B,Ehlert EM,Balaggan KS,Ali RR,Verhaagen J,Wijnholds J (2010) GFAP-driven GFP expression in activated mouse Müller glial cells aligning retinal blood vessels following intravitreal injection of AAV2/6 vectors. PLoS One, 5(8), e12387. 10.1371/journal.pone.0012387.
- Pearson RA,Barber AC,West EL,MacLaren RE,Duran Y,Bainbridge JW,Sowden JC,Ali RR (2010) Targeted disruption of outer limiting membrane junctional proteins (Crb1 and ZO-1) increases integration of transplanted photoreceptor precursors into the adult wild-type and degenerating retina. Cell Transplant, 19(4), 487 - 503. 10.3727/096368909X486057.
- Gualdoni S,Baron M,Lakowski J,Decembrini S,Smith AJ,Pearson RA,Ali RR,Sowden JC (2010) Adult ciliary epithelial cells, previously identified as retinal stem cells with potential for retinal repair, fail to differentiate into new rod photoreceptors. Stem Cells, 28(6), 1048 - 1059. 10.1002/stem.423.
- Smith AJ,Bainbridge JWB,Robbie S,Barker SE,Rubin GS,Moore AT,Ali RR (2010) Improved Retinal Function After AAV Gene Therapy: An Update on the RPE65 Clinical Trial HUMAN GENE THERAPY, 21(4), 504 - 504.
- West EL,Gonzalez CA,Pearson RA,Barber A,Sowden JC,Ali RR (2010) Immune Responses Affect the Survival of Integrated Photoreceptor Precursors Transplanted to the Adult Murine Retina HUMAN GENE THERAPY, 21(4), 513 - 513.
- Mowat FM,Luhmann UF,Smith AJ,Lange C,Duran Y,Harten S,Shukla D,Maxwell PH,Ali RR,Bainbridge JW (2010) HIF-1alpha and HIF-2alpha are differentially activated in distinct cell populations in retinal ischaemia. PLoS One, 5(6), e11103. 10.1371/journal.pone.0011103.
- Barber A,Bainbridge JW,Sowden J,Ali RR,Pearson RA (2010) Gliosis and Extracellular Matrix Proteins: Their Role in Rod Photoreceptor Transplantation in the Degenerating Retina HUMAN GENE THERAPY, 21(4), 511 - 511.
- 1993: Doctor of Philosophy, University College London
- 1988: Bachelor of Science, University College London
- Inherited retinal degeneration
- Retinal disorders
- Age-related macular degeneration
- Anti-sense and morpholino approaches
- Behavioural analysis
- Cell culture
- Cell transplantation
- Clinical trials
- Confocal microscopy
- ES cell manipulations
- Electron Microscopy
- Electrophysiological recording techniques
- Experimental ophthalmology
- Gene Therapy
- Gene and stem cell therapy for retinal disorders
- Laser ablation
- Neural stem cells
- Neurodegenerative diseases
- Retinal cell transplantation
- Retinitis pigmentosa
- Stem Cell Therapy
- Stem cells
- Transgenic mice
- Viral vectors
- Vision Research at UCL
- Visual disorders