Vasiliki Kalatzis PhD Human Genetics, HDR Life Sciences

Course and current status

Group Leader of "Gene Therapy of Retinal Dystrophies" within the Team 01 "Genetics and Therapy of Retinal and Optic Nerve Blindness" directed by Pr Christian Hamel at the Institute of Neurosciences of Montpellier.

Scientific summary

Current research

2011 to date – Gene therapy of retinal dystrophies using human cellular models.

The retina is particularly amenable to gene therapy because it is accessible via relatively non-invasive routes, it is small and enclosed allowing the use of small vector doses, and it is immuno-privileged due to sequestration from the systemic circulation by the blood-retina barrier. Moreover, retinal dystrophies are favourable candidates for gene therapy because they are often monogenic, have characteristic clinical signs allowing an early diagnosis, and progress slowly to blindness allowing a large therapeutic window.

The aim of our work is to generate innovative human retinal cell models for the preclinical development of novel therapies for IRDs. To generate such models, we take skin fibroblasts from patients carrying mutations in a gene of interest that is responsible for a specific retinal dystrophy. We reprogram these cells into induced pluripotent stem cells (iPSc), which we then differentiate into retinal cells such as retinal pigment epithelium (RPE) or photoreceptors.

We have generated iPSc-derived RPE for two different IRDs: choroideremia and retinitis punctata albescens and shown that it is morphologically and functionally characterisitc of the tissue in vivo. Moreover, as it reproduces the biochemical defect of patients, we have shown that it is a powerful tool for screening the efficiency novel therapeutics. More specifically, we use iPSc-derived retinal models for proof-of-concept studies for viral-mediated gene augmentation and gene editing, as a first step towards clinical translation. Such models also represent a first step towards cell therapy approaches.

Selected publications

- Torriano, S., Erkilic, N., Faugère, V., Damodar, K., Hamel, C.P., Roux, A.-F. & Kalatzis, V. (2017) Pathogenicity of a novel missense variant associated with choroideremia and its impact on gene replacement therapy. Hum. Mol. Genet. 18:3573-3584.

- Salinas S, Erkilic N, Damodar K, Molès J-P, Fournier-Wirth C, Nago N, Van de Perre P, Kalatzis, V* & Simonin Y*. (2017) ZIKA virus efficiently replicates in human retinal pigment epithelium and disturbs its permeability. J Virol. 91:e02144-16. *co-last

- Cereso, N., Pequignot, M., Robert, L., Becker, F., De Luca, V., Nabholz, N., Rigau, V., de Vos, J., Hamel, C.P. & Kalatzis, V.  (2014) Proof of concept for AAV2/5-mediated gene therapy in iPSc-derived retinal pigment epithelium of a choroideremia patient. Mol Ther Methods Clin Dev. 1: 14011


Previous research and selected publications

1998-2010 Cystinosis – a lysosomal storage disorder.Characterisation of a novel lysosomal transporter, pathophysiology studies and gene therapy studies using cellular and animal models.

- Hippert, C., Ibanes, S., Serratrice, N., Court, F., Malecaze, F., Kremer, E.J. & Kalatzis, V. (2012) Corneal transduction by intra-stromal injection of AAV vectors in vivo in the mouse and ex vivo in human explants. PLoS One 7(4): e35318.

- Maurice, T., Hippert, C., Serratrice, N., Dubois, G., Jacquet, C., Antignac, C., Kremer, E.J. & Kalatzis, V. (2009) Progressive cystine accumulation in the CNS of a cystinosis animal model results in severe age-related memory deficits. Neurobiol. Aging 30:987-1000.

- Hippert, C., Dubois, G., Morin, C., Disson, O., Ibanes, S., Jacquet, C., Schwendener, R., Antignac, C., Kremer, E.J. & Kalatzis, V. (2008) Gene transfer may be preventive but not curative for lysosomal storage due to a defective transporter. Mol. Ther. 16: 1372-1381.

- Kalatzis, V., Nevo N., Cherqui, S., Gasnier B. & Antignac, C. (2004) Molecular pathogenesis of cystinosis: effect of CTNS mutations on the transport activity and subcellular localization of cystinosin. Hum. Mol. Genet. 13: 1361-1371.

- Kalatzis, V., Cherqui, S., Antignac, C. & Gasnier B. (2001) Cystinosin, the protein defective in cystinosis, is a H+-driven lysosomal cystine transporter. EMBO J. 20: 5940-5949.


1993-1998 Branchial-Oto-Renal syndrome – a syndromic form of deafness. Identification of a novel family of transcription factor termed EYA with widespread developmental roles.

- Kalatzis, V., Sahly, I., El-Amraoui, A. & Petit, C. (1998) Eya1 expression in the developing ear and kidney: Towards the understanding of the pathogenesis of Branchio-Oto-Renal (BOR) syndrome. Dev. Dyn. 213: 486-499. 

- Abdelhak, S.*, Kalatzis, V.,*, Heilig, R., Compain, S., Samson, D., Vincent, C., Weil, D., Cruaud, C., Sahly, I., Leibovici, M., Bitner-Glindzicz, M., Francis, M., Lacombe, D., Vigneron, J., Charachon, R., Boven, K., Bedbeder, P., Van Regemorter, N., Weissenbach, J. & Petit, C. (1997) A human homologue of the drosophila eyes absent gene underlies Branchio-Oto-Renal (BOR) syndrome and identifies a novel gene family. Nature Genet. 15: 157-164.  *co-first

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