Director of Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza”
My scientific interests have been always focused on the enzymology of nucleic acids replication and repair, in normal vs. tumor cells and in viruses infecting them. At the beginning of my career, I have been studying the enzymatic and functional properties of human replicative DNA polymerases (pols) alpha, delta and epsilon and their molecular interactions with the auxiliary factors RP-A, PCNA and RF-C. These studies led to the definition of the mechanism of interaction between DNA pol epsilon and PCNA, the physical isolation of human replication core complexes, the characterization of the concerted action of DNA pol delta, Fen-1 and RP-A in a model for Okazaki fragment maturation, the isolation of two novel DNA pols from mammalian cells: DNA pol theta and lambda and some of the pioneering studies on the ability of human DNA pols in replicating a damaged DNA strand. In the following years, I have devoted my interest to the specialized human enzymes DNA pols lambda, beta and eta, which are involved in DNA repair (BER) and translesion synthesis. We have provided the first evidence for a mechanism depending on DNA pol lambda, PCNA and RP-A for the error-free repair of the major oxidative lesion 8-oxo-guanine and, more recently, we were among the first to address the consequences of ribonucleotides incorporation by these enzymes opposite normal and damaged DNA bases, on the subsequent repair reactions. The other main focus of my research has been the identification of novel targets and drugs for antiviral and anticancer chemotherapy. I have contributed to the development of selective inhibitors against either established targets (HSV TK, HIV-1 RT, HCV NS3 and NS5B, cellular tyrosine kinases such as Abl and Src), or novel ones as exemplified by the human cellular RNA helicase DDX3X. In particular, in collaboration with Prof. Maurizio Botta of the University of Siena, we have provided proof-of-principle for the use of small molecule inhibitors of DDX3X to block HIV-1 replication and, more recently, we have demonstrated that our compounds directed against this cellular enzyme can inhibit the proliferation of a range of RNA viruses, including Dengue, West Nile, HCV. Our compounds are thus first-in-class broad spectrum antivirals acting on a unique cellular target. Along with my passion in performing scientific research, it goes my commitment for popularizing science to the general audience. I wrote three popular science books (in Italian): “Occhio ai Virus” (Beware viruses) on the world of viruses, which was awarded the National Prize for Popularizing Science in the health sciences section in 2013, and “Batteri spazzini e virus che curano” (Waste cleaning bacteria and caretaker viruses) on biotechnological applications, both published by Zanichelli Editore. And “AIDS la verità negata” (AIDS: the denied truth) on the problem of AIDS denial and in general on the AIDS pandemics, edited by Il Pensiero Scientifico Editore, which was awarded the Franz Kafka Literary Prize in the category scientific essays in 2104. I am also often commenting scientific topics on newspapers and magazines, as well as in radio and TV programs. I run a scientific blog on the web for the Agenzia Giornalistica Italiana (AGI) (Italian Journalism Agency).