Ricerc@Sapienza

Main research fields: structural biology and biochemistry.

The mechanism of action of proteins was investigated by using protein crystallography and biochemical characterization. This included the structure-function relationship of enzymes and transporters as well as their role within signalling networks that involves protein-protein recognition and complex formation.

The knowledge of the molecular mechanism exploited by proteins to carry out their function and involved in pathological processes is the starting point to design novel, targeted therapeutic strategies. In this contest, the main endeavour has been the determination of protein structures by protein crystallography and, more recently by single particle cryo-electron microscopy. Protein biochemical and biophysical characterization was carried out using a wide array of methods (kinetics, protein engineering, spectroscopy).

The most relevant results have been:

1. The study by single particle cryo-elecron microscopy of engineered ferritins and of the complex between human ferritin and the CD71 receptor.

2. Structural and functional analysis of enzymes involved in antibiotic biosynthesis, that led to the determination of the structure of a new type of monooxygenase involved in the biosynthesis of aromatic polyketids and of P450 cytochromes involved in the biosynthesis of macrolide antibiotics, erythromycin and oleandomycin.

3. The determination of the structure of murine neuroglobin in different ligation states where a novel mechanism for ligand affinity regulation (heme sliding) was described and the characterization of its reactivity towards nitric oxide.

4. The study by time-resolved crystallography/wide angle X-ray scattering and molecular dynamics of myoglobin, hemoglobin and neuroglobin structural dynamics, that contributed to the to the description by direct detection of the pathway of ligands within the protein matrix and to the unveiling of a complex sub-nanosecond structural dynamics triggered by ligand dissociation.

Ongoing projects: integrative structural biology, biochemical characterization and engineering of i) ferritins as theranostics nanoparticles ii) Steroid 5-a dihydrogenases as oncotargets and pivotal membrane enzymes in neurosteroid biosynthesis iii) interaction between the oncosuppressor HIPK2 kinase and its target, p53.

Ongoing research is focussed on the structure-function relationship of proteins involved in human pathologies, also for theranostics desigs:

1. Complex of plasma proteins with their receptors (haptoglobin, ferritin and LDL-receptor related protein)

2. Steroid 5-a dehydrogenase membrane enzymes

3. Alsin ALS-2 GEF in collaboration with the Politecnico of Turin, with the support of a Telethon Grant

4. SARS-COV-2 antibodies for diagnostics and therapy in collaboration with Takis Biotech with the support of grants from Regione Lazio.