CV Science

Vasiliki Kalatzis PhD Human Genetics, HDR Life Sciences

Course and current status

Since 2021: Inserm Research Director & Team Leader, Inherited visual disorders: from genetics to therapy (Vision Team), INM, Montpellier, France

2011-2020: Inserm Research Scientist & Group Leader, Gene Therapy of Retinal Dystrophies, INM, Montpellier, France

2001-2010: Inserm Research Scientist, Gene therapy of Cystinosis, IGMM, Montpellier, France

1998-2001: Post-doctoral fellow, Genetics & pathophysiology of Cystinosis, Necker Hospital, Paris, France

1993-1997: PhD student, Pasteur Institute, Paris, France

1992-1993: Research Assistant, Queen Elizabeth Hospital, Adelaide, Australia

Scientific summary

Current research (since 2011):

Understanding and treating IRDs

The retina is the tissue that lines the back of the eye that receives, modulates and transmits the light signal to the brain to ensure vision. Inherited retinal diseases (IRDs) are characterised by degeneration of the light-sensing retinal cells, the photoreceptors, which leads to progressive vision loss. IRDs are a genetically and clinically heterogeneous group of disorders with over 300 causative genes. Gene-based therapies hold much promise for IRDs as these disorders are mainly monogenic, have characteristic clinical signs allowing an early diagnosis, and progress slowly to blindness providing a large therapeutic window. However, their complexity and heterogeneity raises challenges for elucidating diseases mechanisms and developing effective treatments.

My team comprehensively studies IRDs at the clinical, genetic and research levels. Notably, we privilege the in-house development of patient-specific induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium and sensory organoid models of IRDs to elucidate genetic variants, decipher pathophysiological pathways and develop novel therapies (gene replacement, genome editing, antisense oligonucleotides, pharmacological).

Selected publications of current research

Damodar et al. (2024) Dual CRALBP isoforms unveiled: iPSC-derived retinal modelling and AAVS/5-RLBP1 gene transfer raise considerations for effective therapy. Mol Ther 32:4319-4336.

Bocquet et al. (2023) TBC1D32 variants disrupt retinal ciliogenesis and are a novel cause of retinitis pigmentosa. JCI Insight 8:e169426.

Sanjurjo-Soriano et al. (2023) USH2A variants causing retinitis pigmentosa or Usher syndrome provoke differential retinal phenotypes in patient-derived organoids. HGG Advances 4:100229.

Sanjurjo-Soriano et al. (2022) Retinoic acid delays initial photoreceptor differentiation and results in a highly structured mature retinal organoid. Stem Cell Res Ther 13:478.

Mamaeva et al. (2021) Novel roles for voltage-gated T-type Ca2+ and ClC-2 channels in phagocytosis and angiogenic factor balance identified in human iPSC-derived RPE. FASEB J 35:e21406.

Diakatou et al. (2021) Allele-specific knockout by CRISPR/Cas to treat autosomal dominant retinitis pigmentosa caused by the G56R mutation in NR2E3. Int J Mol Sci 22:2607.

Sanjurjo-Soriano et al. (2019) Genome editing in patient iPSCs corrects the most prevalent USH2A mutations and reveals intriguing mutant mRNA expression profiles. Mol Ther Methods Clin Dev 17:156-173.

Torriano et al. (2017) Pathogenicity of a novel missense variant associated with choroideremia and its impact on gene replacement therapy. Hum. Mol. Genet. 18:3573-3584.

Cereso et al. (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:  

1. Cystinosis – a lysosomal transport disorder (1998- 2010)

 Characterisation of a novel lysosomal transporter, pathophysiology studies and gene therapy studies using cellular and animal models.

Selected publications

Hippert et al. (2012) Corneal transduction by intra-stromal injection of AAV vectors in vivo in the mouse and ex vivo in human explants. PLoS One 7:e35318.

Maurice et al. (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 et al. (2008) Gene transfer may be preventive but not curative for lysosomal storage due to a defective transporter. Mol. Ther. 16:1372-1381.

Kalatzis et al. (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 et al. (2001) Cystinosin, the protein defective in cystinosis, is a H+-driven lysosomal cystine transporter. EMBO J. 20: 5940-5949.

2. Branchio-Oto-Renal syndrome – a syndromic form of deafness (1993-1998)

Identification of a novel family of transcription factor termed EYA with widespread developmental roles.

Selected publications

Kalatzis et al. (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*, Kalatzis * et al. (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