Biography
From the beginning of my PhD in Rome, my focus has been on understanding the delicate balance of immune regulation. The evolutionary need to activate strong immune responses against pathogens or tumors, while simultaneously preserving tissue integrity, has been a driving force in my career. This passion led me to pursue post-doctoral training with Dr. David Raulet at the University of California, Berkeley, where I had the unique opportunity to study immune regulation within the context of cancer. In 2016, I joined the OHRI and the University of Ottawa to establish my independent research program, dedicated to unraveling the mechanisms behind NK cell regulation and dysfunction, and to devising novel strategies to harness their anti-cancer potential.
Current Projects in the Lab:
1. Regulation of NK Cell Responses in Cancer. We discovered that NK cells are suppressed by the checkpoint receptor PD-1 (Hsu et al., J Clin Invest., 2018) and uncovered that NK cells do not express PD-1 endogenously but acquire it via trogocytosis from neighboring tumor cells (Hasim et al., Science Advances, 2022). We also identified repurposable drugs that activate NK cells through a screening approach (Cortés‑Kaplan et al., Cancers, 2022). We are now investigating more broadly why NK cells lose their effector functions when they are under conditions of sustained stimulation.
2. Cell-Intrinsic Functions of PD-L1. We recently discovered that PD-L1 in cancer cells regulates type I interferon production through metabolic reprogramming, enhancing the efficacy of oncolytic virotherapy (Hodgins et al., J Exp Med, 2022). We are now investigating the biochemical pathways downstream of PD-L1, aiming to elucidate its full impact on cancer metabolism and immunity.
3. Role of ILC2s in Health and Disease in the Ovaries. We are exploring the role of ILC2s in reproductive processes within healthy ovaries and their contribution to immunity against ovarian cancer.
Most Relevant Publications:
Hsu J.+, Hodgins J.J.+, Marathe M., Nicolai C.J., Bourgeois-Daigneault M.C., Trevino T.N., Azimi C.S., Scheer A.K., Randolph H.E., Thompson T.W., Zhang L., Iannello A., Mathur N., Jardine K.E., Kirn G.A., Bell J.C., McBurney M.W., Raulet D.H., Ardolino M. Contribution of NK cells to immunotherapy mediated by PD-1/PD-L1 blockade. The Journal of Clinical Investigation, 2018, 128(10):4654-4688
Hasim M.S.†, Marotel M.†, Hodgins J.J., Vulpis E., Makinson O.J., Asif S., Shih H.Y., Scheer A.K., MacMillan O., Alonso F.G., Burke K.P., Cook D.P., Li R., Petrucci M.T., Santoni A., Fallon P.G., Sharpe A.H., Sciumè G., Veillette A., Zingoni A., Gray D.A., McCurdy A., Ardolino M. When Killers become thieves: trogocytosed PD-1 inhibits NK cells in cancer. Science Advances, 2022, 8(15) †: equal contribution
Hodgins J.J., Abou-Hamad J., O’Dwyer C.E., Hagerman A., Yakubovich E., Tanese de Souza C., Marotel M., Buchler A., Fadel S., Park M., Fong-McMaster C., Crupi M., Makinson O.J., Kurdieh R., Rezaei R., Dhillon H.S., Ilkow C., Bell J.C., Harper M-E., Rotstein B.H., Auer R.C., Vanderhyden B., Sabourin L., Bourgeois-Daigneault M.C., Cook D., Ardolino M. PD-L1 promotes oncolytic virus infection via a metabolic shift that inhibits the type I interferon pathway. The Journal of Experimental Medicine, 2024, 221 (7): e20221721