FRRB Project 1734478 - Multiple sclerosis: translating alternative splicing events into therapeutic targets and biomarkers.


Name and Surname of PI

Elvezia Maria Paraboschi

Project Acronym


Project ID


Host Institution

Istituto Clinico Humanitas - Milan

Pathology of Interest

Multiple Sclerosis

Research Area

Autoimmune Diseases

Project Start Date

1 May 2021

Project End Date

30 April 2024


€ 600.000,00

Type of Project



The molecular mechanisms involved in multiple sclerosis (MS) development have not been fully elucidated. Increasing evidence, however, highlights the role of alternative splicing (AS) in disease predisposition. Splicing is one of the mechanisms used by the cell to process RNA molecules before being translated into proteins. My working hypothesis is that the dysregulation of splicing and backsplicing processes, the latter leading to the formation of atypical circular RNA molecules (circRNAs), may affect MS pathogenesis by altering the repertoire of translated proteins, eventually leading to neurodegeneration and immunogenicity. The project has the goal to analyze the landscape of AS and circRNAs, and to integrate regulatory genetic and epigenetics (external modifications to DNA that regulate gene expression) data, to gain insights on how these mechanisms are involved in MS. Moreover, dysregulated AS isoforms and circRNAs could be used as biomarkers specific of the disease.