Ricerc@Sapienza

My research activity has mainly concerned vitamin B6 metabolism, in humans and bacteria, and the mechanism, structure, regulation, metabolic role and inhibition of vitamin B6-dependent enzymes. At present, my interest is focused on the mechanisms of vitamin B6 homeostasis. On one side, I am investigating the transcriptional regulation of vitamin B6 biosynthesis and recycling pathways, focusing on bacterial organisms and the chimeric MocR proteins, which are PLP-binding transcriptional factors involved in the activation or repressor of vitamin B6 metabolism genes. On the other hand, I am studying the role of pyridoxal 5’-phosphate (PLP) carrier proteins, such as pyridoxine 5’-phosphate oxidase (PNPOx), pyridoxal kinase (PLK) and YggS, in controlling PLP homeostasis and delivery to apoenzymes in bacteria and humans. Besides, I am also committed to characterising the molecular basis of vitamin B6-dependend epilepsy, focusing my attention on missense mutations of human PNPOx. In this context, I am collaborating with clinicians to characterise novel mutations and correlate medical symptoms to the biochemical profile of patients. In recent years, I turned my attention to the role of serine hydroxymethyltransferase in the metabolic reprogramming of cancer cells, participating to two 3-year research programs funded by the Italian Association for Cancer Research (AIRC). My contribution to this field consisted in the study of the catalytic, structural and regulatory properties of both cytosolic and mitochondrial isoforms of the enzyme, the experimentation of novel inhibitors and the devise of in vivo activity assays. Lately, I have been involved in a project concerning the use of B6-enzymes as tools in the biosynthesis of unnatural amino acids and their intracellular incorporation in proteins and peptides.