Ivano Amelio-The p53 family in the cancer cell response to hypoxia
Auditorium CEINGE - May 23 at 12.30- Seminar of Ivano Amelio
Title: “The p53 family in the cancer cell response to hypoxia”.
Host Researcher: Prof. Caterina Missero.
Biography
Ivano Amelio is currently a Senior Scientist at the University of Cambridge (UK) in the Medical Research Council (MRC) Toxicology Unit. He received his PhD in Biochemistry and Molecular Biology from University of Rome Tor Vergata (Italy) in 2011, elucidating a novel microRNA-mediated mechanism regulating the balance of epidermal cell proliferation/differentiation (Amelio et al, JCB 2012; Amelio et al, CDDis 2013).
His current research focuses in understanding the fundamental mechanisms of cellular and tissue response to injury caused by exposure to environmental and therapeutic toxicants, with a particular emphasis on the function of the p53 family (p53, p63, p73). His experimental approach involves integration of multiple in vitro and in vivo methods including system biology (genomic screens, metabolomics), generation and characterization of genetic modified animal models and computational tools for analysis of large-scale datasets. His major contributions include the identification of specific functions for p53 family members in cellular stress response, in particular mediated by p73 regulation of cancer metabolism (Amelio et al, Oncogene, 2013; Amelio et al, TiBS 2014; Amelio et al, CDD 2016) and angiogenesis (Amelio et al, PNAS 2015; Amelio & Melino TiBS 2015). He has also been exploring integration of p53 signalling with microenviromental hypoxia, revealing a novel GOF effect of p53 mutants in hypoxic tumours (Amelio* et al; in revision at PNAS, *corresp. author). By employing computational tools his work also explored polypharmacology and drug repositioning to improve drug safety and minimize the risk of potential side effects of the prospective drugs (Amelio et al, Oncotarget 2015; Landre et al, Mini Rev Med Chem, 2015; Amelio et al Curr Drug Targets, 2017).
(from University of Cambridge Web Site)
Seminar Abstract
The tumour suppressor protein p53, cooperated by its family members p63 and p73, has an essential role in the response to toxic injury. Somatic cells largely rely on p53 to overcome genotoxic stress and to maintain genomic integrity. Inactivation of p53 is indeed considered the “point of no return” for genomic instability.
In addition to the canonical p53 control of cell cycle arrest/apoptosis, recent evidence indicates that upon cellular stress p53 coordinates highly diverse processes, such as cellular metabolism, redox homeostasis, and inter-cellular communication and interaction with the external micro‐environment. Hence, p53 is a critical factor in maintaining cellular homeostasis following a wide range of (micro)-environmental insults.
I will discuss the contribution of functional and abnormal p53 family signalling to the cellular response to hypoxia. Our work demonstrated that the p53 family participates to a complex interplay with the hypoxia-inducible factor (HIF) signalling, influencing shape and function of microenvironment as well as cellular properties. Our data indicate that the p53 family/HIF-1 molecular axis could have major relevance in cancer pathogenesis.