Research
My research career has been centered around my interest in metabolism. From my graduate work abroad, I have gained extensive experience in the field of metabolism and applied mass spectrometry-based proteomics to identify enzyme targets of protein oxidation and how this modification impacts in their function in the context of neurodegeneration. By obtaining a start-up grant from the Italian Ministry of Health to join a laboratory leader in mitochondrial metabolism, I gained strong experience in the field of metabolism and mastered mass spectrometry-based techniques to evaluate metabolic changes in cell culture and in tissue. Then, I moved my interest toward dissecting the basic fundamentals of the physiology of macrophages in terms of the metabolic pathways and carbon routes preferentially used during their different types of activation, which I learned by visiting internationally-known research laboratories. I became engaged in the study of integrated metabolic pathways that are required for the synthesis of immunometabolites such as citrate and glutamine, which led to the identification of glutamine synthetase (GS) as a novel metabolic checkpoint of macrophage function. With this respect, my group was able to validate the translational potential of these findings, demonstrating that pharmacological targeting of GS in murine tumor models is a feasible strategy to reprogram macrophage’s function and reduce metastasis. Currently I am investigating physiological and pathological scenarios where macrophages metabolically change, are metabolically conditioned by the environment they are in, and where they sculpt that environment to impact the function of cancer cells. By developing strong models and expertise in a variety of metabolic techniques, including metabolic flux analysis, unbiased and targeted metabolomics analysis, and carbon isotopomer tracing techniques, my group identified N- acetyl aspartate as a novel signalling metabolite in the ovarian tumor microenvironment and NMDA receptor a novel target for bioelectric modulation of macrophage function. My experience in metabolism leaves me well positioned to identify new and exciting metabolic pathway targets for therapeutic exploitation.
Collaborations
o Cancer Immunology: M. Mazzone (VIB KU LEUVEN), DC. Hooper (Thomas Jefferson University), Daniel McVicar (NCI; Frederick, MD USA). o Hypoxia: J. Aragones-Lopez (University of Madrid). o Cancer metabolism: C. Frezza (University of Cologne), Anna Maria Porcelli (University of Bologna, Italy). o Immunity: Antonella Viola, (University of Padua), Barbara Molon (University of Padua). o Mitochondria: Andrea Rasola, Marcella Canton, Anna Raffaello (University of Padua). o Clinical Oncology: Stefano Indraccolo (University of Padua), Gennaro Cormio (University of Bari Aldo Moro) o Genetics: Graziano Pesole (University of Bari); Giuseppe Gasparre (University of Bologna). o Pharmacology: Monica Montopoli (University of Padua). o Neurodegeneration: D. Allan Butterfield (University of Kentucky, USA).