Dottorato in EXPERIMENTAL MEDICINE

email: ricciarda.galandrini@uniroma1.it

Research interests have been focused on human Natural Killer (NK) cells in pathophysiological contexts. In particular, the following aspects have been addressed: Molecular mechanisms regulating the activation of cytolytic machinery in NK cells, focusing on small G protein- and lipid-modifying enzymes-regulated signaling pathway. These studies added new insights on the signaling intermediates regulating discrete steps of the cytotoxic process Role of NK cell anti-tumor activity in therapeutic settings based on tumor targeting monoclonal antibodies. The studies elucidated 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. Memory responses in innate immune compartment. These studies revealed the effect of therapeutic antibodies, endogenous auto-antibody and anti-viral antibodies, in driving the expansion and functional activation of an hyperfunctional and long-living NK cell population called “memory” NK cells. Research results have uncover previously unrecognized mechanisms of NK cell plasticity also providing an experimental framework for the rational design of improved strategies of exploitation of NK cells in cancer immunotherapy. Impact of vaccination on NK cell compartment. We revealed that mRNA based Sars-Cov2 vaccine stably affect NK cell phenotype and functions highlighting the impact of genetic and environmental host-related factors in modulating NK cell susceptibility to post-vaccinal Fc-dependent functional impairment. Keywords Natural Killer (NK) cells anti-tumor immune response trained immunity Progetti di Ricerca UNRAVELING PHENOTYPIC AND FUNCTIONAL HETEROGENEITY OF HUMAN MEMORY NK CELLS Analysis of the molecular mechanisms underlying the priming of NK cells for IFN-gamma production upon glycoengineered mAb-mediated high affinity ligation of FcgammaRIIIA/CD16 Gruppi di ricerca - Responsabile Pathophysiology of Natural Killer cells in primary immunodeficiency