PRIN 2017 Passafaro - A multidisciplinary approach to study protocadherin 19: from neuronal function to the "cellular interference" pathogenic mechanism (DSB.AD004.242)
Area tematica
Area progettuale
Neuroscienze (DSB.AD004)Struttura responsabile del progetto di ricerca
Responsabile di progetto
MARIA PASSAFARO
Telefono: 02-50316973
E-mail: maria.passafaro@in.cnr.it
Abstract
The focus of this project is to investigate the function of protocadherin 19 (PCDH19) in neuronal physiology and disease. We will clarify the role of PCDH19 in the formation of neuronal circuits and provide insights into the unique pathogenic model of the "cellular interference". Finally, we will test two alternative genetic approaches to rescue PCDH19-related disease.
Obiettivi
1.Recruitment and clinical, EEG, neuropsychological study of patients carrying PCDH19 mutations to improve our understating of the heterogenous phenotype associate to PCDH19 gene mutations. Molecular genetic studies aims to also uncover patients carrying mosaic mutations either male or females. MRI study including brain morphologic, white matter analysis and connectivity might help to understand human, in vivo, PCDH19 role in brain development and function.
2. To define the synaptic function of PCDH19 in vivo and analyse whether and how the mosaic expression of PCDH19 might affect the correct functioning of brain circuits.
3. To create an Italian biobank of Stem cells from Human Exfoliated Deciduous teeth (SHED). The biobank will collect and store SHED from PCDH19-FE patients.
4. To generate and characterize disease-relevant cellular models for PCDH19-FE exploiting patient-derived iPSCs and SHED.
5. To develop new strategies based on CRISPR/Cas9 technology able to rescue the "cellular interference". These potential therapies will be validated in patients' cells and a mouse model.
Data inizio attività
29/08/2019
Parole chiave
PCDH19, -, -
Ultimo aggiornamento: 16/04/2025