My research aims to reveal how cancer cells evolve to proliferate and evade cell death in order to develop new therapeutic strategies, in particular for the treatment of breast cancer. I am interested in understanding the contribution of cellular metabolism to cancer cell survival and proliferation.
The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs. Mol Cell (2011) 43 (3): 432-48. PMID: 21737329
A tangled web of ubiquitin chains: breaking news in TNF-R1 signaling. Mol Cell (2009) 36(5):736-42. Review. PMID: 20005838
Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels. J Cell Biol (2006) 175(6):901-11 *co-author. PMID: 17178908
Cancer cells evolve to proliferate and evade cell death. Tumours indeed not only have an amazing ability to adapt to any kind of environment and nutrient condition, but they can actually re-program themselves to take advantage of any situation to grow and proliferate.
I hope to reveal how cancer cells can achieve this sheltered status in order to develop new therapeutic strategies, in particular for the treatment of breast cancer. Specifically, I am interested in understanding the contribution of cellular metabolism to cancer cell survival and proliferation.
The vast majority of tumours rely on a switch in metabolism towards anaerobic glycolysis to produce enough building blocks for their growth and successive divisions. Anaerobic glycolysis is a metabolic choice of diverting substrates away from the mitochondria despite the presence of oxygen, to allow the biosynthesis of all the components required for growth starting from glycolytic metabolic intermediates.
Another central aspect of cancer cell biology that I am investigating is inflammation driven malignant transformation. Cancer and inflammation have a close, complex relationship; my research aims to investigate whether inflammation can rewire cellular metabolism, causing malignant transformation.
The final scope of this line of my research is to design better combination therapy to limit inflammation driven malignant transformation, possibly combining anti-inflammatory drugs with drugs targeting different metabolic pathways.
Loss of voltage-gated hydrogen channel 1 expression reveals heterogeneous metabolic adaptation to intracellular acidification by T cells Coe D, Poobalasingam T, Fu H et al. JCI Insight (2022) 7(7)
Mitochondrial pyruvate carrier abundance mediates pathological cardiac hypertrophy Fernandez-Caggiano M, Kamynina A, Francois AA et al. Nature Metabolism (2020) 2(7) 1223-1231
The breast cancer oncogene IKKε coordinates mitochondrial function and serine metabolism Xu R, Jones W, Wilcz-Villega E et al. EMBO Reports (2020) 21(7)
Macrophages induce malignant traits in mammary epithelium via IKKε/TBK1 kinases and the serine biosynthesis pathway Wilcz-Villega E, Carter E, Ironside A et al. EMBO Molecular Medicine (2020) 12(7)
RIPK1 and Caspase-8 Ensure Chromosome Stability Independently of Their Role in Cell Death and Inflammation Liccardi G, Ramos Garcia L, Tenev T et al. Molecular Cell (2019) 73(7) 413-428.e7
Molecular mechanisms of cell death: Recommendations of the Nomenclature Committee on Cell Death 2018 Galluzzi L, Vitale I, Aaronson SA et al. Cell Death and Differentiation (2018) 25(7) 486-541
Ubiquitin-Mediated Regulation of RIPK1 Kinase Activity Independent of IKK and MK2 Annibaldi A, Wicky John S, Vanden Berghe T et al. Molecular Cell (2018) 69(7) 566-580.e5
The unconventional myosin CRINKLED and its mammalian orthologue MYO7A regulate caspases in their signalling roles Orme MH, Liccardi G, Moderau N et al. Nature Communications (2016) 7(7)
Aerobic glycolysis: Beyond proliferation Jones W, Bianchi K Frontiers in Immunology (2015) 6(7)
Essential versus accessory aspects of cell death: Recommendations of the NCCD 2015 Galluzzi L, Bravo-San Pedro JM, Vitale I et al. Cell Death and Differentiation (2015) 22(7) 58-73For additional publications, please click here
I obtained my PhD in Molecular Medicine (2006) in Ferrara, Italy, studying the role of mitochondrial signalling and metabolism in different pathophysiological conditions, under the supervision of Prof. Rosario Rizzuto. I then moved for a short postdoctoral period to the INSERM in Paris, to study the role of the mitochondria in hepatocellular tumour formation.
In 2007 I obtained a FEBS long-term postdoctoral fellowship to join the apoptosis laboratory at the Institute of Cancer Research, London, led by Prof. Pascal Meier. During my post-doctoral training, I focused on the family of protein IAPs (Inhibitor of Apoptosis) and their role in inflammation and cancer. As their name suggests, this family of proteins has a strong anti-apoptotic role and we studied their role in chemotherapy-induced death of cancer cells. Thus we identified the Ripoptosome, a newly described protein complex, which plays a crucial role in cell death induction, both via apoptosis and necroptosis.