Hossein Dehghan Banadaki

I'm a biotechnologist with a passion for understanding how to regenerate the retina. My journey took me from Iran to Italy, where I earned my BSc and MSc, respectively. I'm particularly interested in figuring out how to fix retinal dystrophies, especially those with inherited roots. My research has focused on using clever genetic tricks to treat eye diseases like EYS-associated RP, and I've also studied how specific gene mutations mess with the vision.
When I'm not in the lab, you can find me lost in a good book, spiking a volleyball, or cheering on my football team. Also, nature is my happy place, so I love spending time outdoors.

Allele-specific invalidation of dominant-negative mutations in PRPH2

Central areolar choroidal dystrophy (CACD) is caused by autosomal dominant pathogenic variants in PRPH2, encoding a tetraspanin protein (peripherin-2) present in the photoreceptor outer segments. Whilst some PRHP2 mutations act in via haploinsufficiency, other variants exert their pathogenicity via a dominant-negative mechanism. For the latter group, allele-specific degradation of the mutant transcript is expected to be of therapeutic benefit. Based on preliminary data for one recurrent missense mutation in PRPH2, as well as locus-sequencing data that identified common polymorphisms in cis with the mutation, we have identified a range of therapeutic targets. The PhD student (DC7) aims to identify which of the many PRPH2 mutations act in a dominant-negative manner, and in parallel will realize an allele-specific inhibition of the expression of the mutant protein via antisense oligonucleotides (ASOs). Via VIP (visible immunoprecipitation) assays DC7 will study the ability of mutant peripherin-2 to interact with other peripherin-2 and/or ROM1 proteins. In parallel, ASOs will be designed targeting the mutation and/or variants elsewhere in the gene that are in cis with the pathogenic variant. Allele-specificity and efficacy will first be measured in transfection assays, and later optimized in an established patient-derived RO model.