This proposal aims to explore the role of autophagy and nucleophagy within the different epidermal layers. The research project will investigate the role of the ASPP proteins during epidermal homeostatic process and how they cross-talk with the AKT signalling pathway during epidermal autophagy. In particular we are interested in how this cross-talk might influence the inflammatory response in skin. Finally we will test if skin conditions affecting the integrity of skin barrier or dermal-epidermal junction may be characterized by impairment of the autophagy pathway and whether targeting this process may ultimately provide new treatment options.
Constitutive autophagy and nucleophagy during epidermal differentiation. Akinduro O, Sully K, Patel A, Robinson DJ, Chikh A, McPhail G, Braun KM, Philpott MP, Harwood CA, Byrne C, O'Shaughnessy RF and Bergamaschi D. J Invest Dermatol. 2016 Mar 25
Chikh A, Sanzà P, Raimondi C, Akinduro O, Warnes G, Chiorino G, Byrne C, Harwood CA and Bergamaschi D. iASPP is a novel autophagy inhibitor in keratinocytes. J Cell Sci. 2014; 127(14):3079-93.
Tordella L et al & Lu X. ASPP2 suppresses squamous cell carcinoma via RelA/p65-mediated repression of p63. Proc Natl Acad Sci USA 2013; 110: 17969-74
Naeem AS, Zhu Y, Di WL, Marmiroli S, O’Shaughnessy RF. AKT1-mediated Lamin A/C degradation is required for nuclear degradation and normal epidermal terminal differentiation. Cell Death Differ. 2015; 22(12):2123-32.
Sully K, Akinduro O, Philpott MP, Naeem AS, Harwood CA, Reeve VE, O’Shaughnessy RF & Byrne CR. The mTOR inhibitor rapamycin opposes carcinogenic changes to epidermal Akt1/ PKBα isoform signaling. Oncogene 2013; 32(27):3254-62.