Silvestro Conticello

I started in Catania where, after training as a medical doctor, I moved to basic research with a PhD in biochemistry. My interest in gene diversification began at the Weizmann Institute, as a postdoc with Mike Fainzilber, where I set up one of the first projects to analyse the diversity and the evolution of conotoxins, a large group of neuroactive molecules from the venoms of Conus snails. 

My fascination with genetic hypervariability and its role in the evolution of somatic cells then brought me to the lab of Michael Neuberger at the MRC-LMB in Cambridge, where I worked on the molecular mechanisms of antibody diversification and on the evolutionary and structural origins of the AID/APOBECs. a family of DNA/RNA editors, as well as on the pathway that HIV uses to counteract the APOBEC3s. 

Since 2007 I have led the “Molecular Mechanisms of Oncogenesis” unit at the Core Research Laboratory in ISPRO (Florence), and I am a Primo Ricercatore at the Institute of Clinical Physiology - CNR (Pisa). Here my work has gradually moved from the physiology of these enzymes to their pathological consequences and to their practical exploitation. We showed that APOBEC1 is mutagenic and leaves a traceable signature in human tumours, and that the APOBECs edit the RNA genome of SARS-CoV-2, contributing to its evolution. In parallel, we have engineered APOBEC variants that reduce the off-target mutations of Base Editors, and we are developing systems for programmable, site-directed RNA editing. The need to quantify APOBEC-induced damage led us to Oxford Nanopore sequencing, where we were the first to apply native, low-coverage whole-genome sequencing to cell-free DNA, extracting genetic, epigenetic and fragmentomic information for liquid biopsy. C-to-U RNA editing by APOBEC1 drew me into the wider world of post-transcriptional modifications, and we now use direct RNA sequencing to map the epitranscriptome of solid tumours, a layer of information still unexplored in cancer.

ORCID ID: https://orcid.org/0000-0002-4244-1846