Research Groups

Human Molecular Genetics

Research Interests and Description

Group Leader: Franco Pagani, MD, PhD

Group Members

Research Interests

Regulation of pre-mRNA processing in human diseases.

Description of Research

U1-snRNA-mediated rescue of coagulation factor VII expression impered by the IVS7+5G>A mutation.

The lab focuses on studies of normal and pathological pre-mRNA processing. We aim to evaluate the genes involved in several disorders, including Cystic Fibrosis and coagulation deficiencies in order to unravel the mechanism by which mutations affect pre-mRNA processing and provide appropriate therapeutic correction strategies. In collaboration with genetic screening laboratories, we are systematically evaluating the effect of the exonic substitutions and intronic variants in Coagulation Factor genes in order to improve diagnosis and identify potential targets for therapeutic correction. Modified U1 snRNAs are actively tested for correction of exon skipping caused by different types of mutations in coagulation deficiencies, Cystic Fibrosis and Spinal Muscolar Atrophy. Another research line is dedicated to understanding the relationship between pre-mRNA splicing and miRNA processing. We are evaluating the competition between these two processes in the biosynthesis of specific cancer-associated miRNAs. Lastly, using biochemical and molecular approaches we are studying the alternative splicing regulation mediated by exonic and intronic regulatory elements in the TMEM16a, a Ca-dependent Cl channel involved in several human disorders.

Recent Publications

Pastor, T., Pagani, F. 2011. Interaction of hnRNPA1/A2 and DAZAP1 with an Alu-Derived Intronic Splicing Enhancer regulates ATM aberrant splicing. PLoS One 6, e23349 [Epub ahead of print] PubMed link

Pinotti, M., Bernardi, F., Dal Mas, A., Pagani, F. 2011. Rna-based therapeutic approaches for coagulation factor deficiencies. J Thromb Haemost PMID, 21854538 [Epub ahead of print] PubMed link

Pastor, T., Dal Mas, A., Talotti, G., Bussani, E., Pagani, F. 2011. Intron cleavage affects processing of alternatively spliced transcripts. RNA 17, 1604-1613 PubMed link

Crotti, L., Lewandowska, M.A., Schwartz, P.J., Insolia, R., Pedrazzini, M., Bussani, E., Dagradi, F., George, A.L., Pagani, F. 2009. A KCNH2 branch point mutation causing aberrant splicing contributes to an explanation of genotype-negative long QT syndrome. Heart Rhythm 6, 212-218 PubMed link

Pastor, T., Talotti, G., Lewandowska, M.A., Pagani, F. 2009. An Alu-derived intronic splicing enhancer facilitates intronic processing and modulates aberrant splicing in ATM. Nucleic Acids Res, 37, 7258-7267 PubMed link