Carla Olivieri, Associate Professor, P.I.
Anna Sbalchiero, Specializzanda in Medical Genetics, Senior Fellow;
Claudia Cantarini, Senior Fellow;
Chantal Nardiello, Postgraduate;
Lorenzo Cassinelli, Undergraduate;
Marta Catania, Postgraduate;
Martina Coffa, Postgraduate.
The lab, headed by Prof. Carla Olivieri, mainly focuses on the study of a rare disease, Hereditary Hemorrhagic Telangiectasia (HHT), a vascular dysplasia affecting endothelium and leading to telangiectases and Vascular Arteriovenous Malformations. HHT is an autosomal dominant disorder with a prevalence of about 1:5000 worldwide.
- Whole Genome Sequencing (WGS) in Not Found Patients, in whom the standard sequencing of coding regions and exon-intron boundaries of the HHT-related genes (ACVRL1, ENG, SMAD4, GDF2) did not point out the disease-causing variant. Using WGS we analyse cryptic regions of these genes. In addition to an early diagnosis, the study will allow the identification of novel pathogenic mechanisms as well as novel rare variants not yet related to the disease.
- Circulating miRNAs analysis. We highlighted the presence of dysregulated miRNAs in Patients’ plasma and in vitro validation experiments are ongoing. Circulating miRNAs study paves the way to novel early diagnosis tools and therapeutic approaches.
- Dysregulated miRNAs in Patients’ ECs and SMCs cells. This study is ongoing in collaboration with dr. M. Climent-Salarich (Fondazione Humanitas).
- Telomere length in HHT Patients. There are no literature data on the topic and we aim at filling this gap, to clarify in HHT Patients are exposed to a premature cell-aging risk.
- Cytokines analysis. In collaboration with Prof. M. Borgatti (University of Ferrara) we are studying the inflammatory Cytokines level in HHT Patients’ plasma. These data are completely new. - Functional studies on rare Variants of Uncertain Significance.
- ACMG guidelines for HHT revision.
Other collaborations concern Systemic Sclerosis and Werner Syndrome.
Grignaschi S, Sbalchiero A, Spinozzi G, Palermo BL, Cantarini C, Nardiello C, Cavagna L, Olivieri C. Endoglin and Systemic Sclerosis: a PRISMA-driven systematic review. Submitted to Frontiers in Medicine
Sbalchiero A, Abu Hweij Y, Mazza T, Buscarini E, Scotti C, Pagella F, Manfredi G, Matti E, Spinozzi G, Olivieri C. Hereditary hemorrhagic telangiectasia: First demonstration of a founder effect in Italy; the ACVRL1 c.289_294del variant originated in the country of Bergamo 200 years ago. Mol Genet Genomic Med. 2022 May 27:e1972. doi: 10.1002/mgg3.1972. Epub ahead of print. PMID: 35620871.
Plumitallo S, Ruiz-Llorente L, Langa C, Morini J, Babini G, Cappelletti D, Scelsi L, Greco A, Danesino C, Bernabeu C, Olivieri C. Functional analysis of a novel ENG variant in a patient with hereditary hemorrhagic telangiectasia (HHT) identifies a new Sp1 binding-site. Gene. 2018 Mar 20;647:85-92. doi: 10.1016/j.gene.2018.01.007. Epub 2018 Jan 4
Olivieri C, Pagella F, Semino L, Lanzarini L, Valacca C, Pilotto A, Corno S, Scappaticci S, Manfredi G, Buscarini E, Danesino C. Analysis of ENG and ACVRL1 genes in 137 HHT Italian families identifies 76 different mutations (24 novel). Comparison with other European studies. J Hum Genet. 2007;52(10):820-9. Epub 2007 Sep 5.
Lesca G, Olivieri C, Burnichon N, Pagella F, Carette MF, Gilbert-Dussardier B, Goizet C, Roume J, Rabilloud M, Saurin JC, Cottin V, Honnorat J, Coulet F, Giraud S, Calender A, Danesino C, Buscarini E, Plauchu H; French-Italian-Rendu-Osler Network. Genotype-phenotype correlations in hereditary hemorrhagic telangiectasia: data from the French-Italian HHT network. Genet Med. 2007 Jan;9(1):14-22.