Medical Genetics and RNA Biology Lab

The challenge

Recent advances in sequencing technologies, gene expression analysis and data science opened up new lines of investigation in the pathogenic mechanisms underlying both monogenic diseases and multifactorial complex conditions, which often cluster in families even if they do not have a clear-cut pattern of inheritance. Genome-wide association studies allowed for the identification of different profiles of genetic risk for conditions that are still poorly understood – such as Parkinson diseases or multiple sclerosis – and contributed to unveil the key role played by splicing and back-splicing dysregulation, as well as non-coding RNA molecules, in diseases pathogenesis.

Main research areas

Genetic predisposition to complex diseases

We are interested in understanding the genetic components of the predisposition to complex pathological conditions such as Parkinson diseases, multiple sclerosis, juvenile myocardial infarction – a project conducted in collaboration with the Broad Institute of MIT and Harvard – and Primary Biliary Cholangitis (PBC), a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. We are particularly interested in the characterization of pathogenic mechanisms that interfere with splicing and transcript stability. In the last three years we have also been investigating the genetic predispositions to the severe forms of COVID-19. Our approach to the study of complex traits is often based on genome-wide screens (genome-wide association studies, as well as RNA, exome, and genome sequencing), integrating the diverse omics layers with supervised or unsupervised strategies (including the implementation of artificial intelligence procedures).

Role of non-coding RNAs in the pathogenesis of human diseases

We are interested in investigating the role of miRNAs and of other non-coding RNAs in the pathogenesis of different diseases, such as non-syndromic hearing loss, Parkinson diseases and multiple sclerosis. In these pathological contexts, we try to identify non-coding RNAs that play a role in pathogenesis, to study their expression profile and biogenesis, to predict and experimentally validate their function and interaction with targets. In addition, we are interested in the study of circular RNAs as potential biomarkers.

Novel approaches for the molecular diagnosis of cancer

We are working at the identification of tumor-derived elements in biologic fluids for the early detection and molecular characterization of prostate cancer. We are also collaborating to a radiomics project aimed at combining FDG-PET quantitative analysis with pathology data, somatic mutations, chromosomal rearrangements, patient outcome and therapy response in lung cancer.