Ricerc@Sapienza

Research interests have been aimed at understanding the molecular mechanisms regulating the activation of Natural Killer (NK) cell cytolytic machinery by focusing on small G protein (rac1, Arf6)- and lipid-modifying enzymes (SHIP-1, PI5KI)-dependent signals. These studies added new insights on the signaling intermediates acting at different steps of the cytotoxic process (i.e. granule polarization vs exocytosis). More recently, research interests have been focused on the role of NK cells in antitumor activity of therapeutic antibodies. The findings elucidated a previously unrecognized molecular mechanisms leading to the functional exhaustion of NK cells and offer a mechanistic basis of resistance to therapeutic antibodies. The studies also highlight the capability of next generation defucosylated monoclonal antibodies to potentiate immunoregulatory functions of NK cells through microRNA-mediated regulation of PI3K/mTOR pathway.

Recent studies also elucidated the capability of tumor targeting therapeutic antibodies to selectively drive the in vitro expansion and the functional activation of “memory” NK population with enhanced antitumor potential.