Autophagy impairment and barrier integrity signalling pathways in chronic inflammatory skin diseases

Abstract

This proposal aims to explore the role of epidermal autophagy streams occurring towards the upper layers during skin development. The research project will investigate the role of the ASPP proteins during this epidermal homeostatic process and how they cross-talk with the AKT signalling pathway. In particular we are interested in how this cross-talk may influence the inflammatory response in skin. Finally we will seek evidence that chronic inflammatory skin conditions targeting the integrity of the skin barrier may be characterized by impairment of the autophagy pathway and that targeting this process may provide new directions for treatment.





References:
[1]

Akinduro O, Sully K, Chikh A, Robinson DJ, Patel A, McPhail G, Braun K, Philpott MP, Harwood CA,  Carolyn Byrne, O'Shaughnessy RFL & Bergamaschi D. Constitutive autophagy during epidermal development. (#2014AUTO0166R In revision with Autophagy)

[2]

Chikh A, Sanzà P, Raimondi C, Akinduro O, Warnes G, Chiorino G, Byrne C, Harwood CA, Bergamaschi D. iASPP is a novel autophagy inhibitor in keratinocytes. J Cell Sci. 2014; 127(14):3079-93.

[3]

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

[4]

Sully K, Akinduro O, Philpott MP, Naeem AS, Harwood CA, Reeve VE, O’Shaughnessy RFL & Byrne CR. The mTOR inhibitor rapamycin opposes carcinogenic changes to epidermal Akt1/ PKBα isoform signaling. Oncogene. 2013 Jul 4; 32(27):3254-62.

[5]

Naeem AS, Zhu Y, Di WL, Marmiroli S, O’Shaughnessy RFL. Akt1-mediated Lamin A/C degradation is required for nuclear degradation and normal epidermal terminal differentiation. Accepted, Cell Death and Differentiation


Biological Areas:

Cell Biology
Ageing

BBSRC Area:

Genes, development and STEM approaches to biology