Dr Ryan O'Shaughnessy

Profile

Dr Ryan O'Shaughnessy is a Senior Lecturer in the Centre for Cell Biology and Cutaneous Research. He leads a research programme focused on understanding molecular mechanisms of skin barrier function and through these insights, developing new therapies for diseases of skin barrier function, with particular emphasis on the ichthyoses, eczema and skin cancer.

Ryan completed his PhD in keratinocyte biology at Cancer Research UK, before postdoctoral training at Columbia University, NY and Queen Mary University of London. He started his skin barrier laboratory in 2008 at the UCL Great Ormond Street Institute of Child Health, and in 2012 was the Academic Lead of the Livingstone Skin Research Centre, a research centre dedicated to the study of childhood skin disease. He was awarded a Society of Investigative Dermatology Kligman fellowship in 2002 and the British Society of Investigative Dermatology Young Investigator Award in 2009.

Memberships include the European Society of Dermatological Research and the European Epidermal Barrier Research Network, and the UK Translational Research Network in Dermatology (UK TREND) and he is on the Editorial Board of Experimental Dermatology and on the Committee of the British Society of Investigative Dermatology. 

Summary

My laboratory is interested in how the outermost layer of the skin, the epidermis, forms a barrier to the external environment, and how changes in this epidermal barrier function contribute to a range of epidermal skin disease from eczema to skin cancer. 

Key projects include:

1. Role of the AKT kinases in skin barrier function and skin cancer
2. Role of AKT1 in epidermal terminal differentiation processes
3. Mechanisms of hyperkeratosis in the genetic skin disease

Teaching

Research

Research Interests:

My laboratory is interested in how the outermost layer of the skin, the epidermis, forms a barrier to the external environment, and how changes in this epidermal barrier function contribute to a range of epidermal skin disease from eczema to skin cancer. Key projects include:

1. Role of the AKT kinases in skin barrier function and skin cancer

2. Role of AKT1 in epidermal terminal differentiation processes

3. Mechanisms of hyperkeratosis in genetic skin disease 

Publications

• Naeem AS et al., A mechanistic target of rapamycin complex 1/2 (mTORC1)/V-Akt murine thymoma viral oncogene homolog 1 (AKT1)/cathepsin H axis controls filaggrin expression and processing in skin, a novel mechanism for skin barrier disruption in patients with atopic dermatitis. J Allergy Clin Immunol. 2017 Apr;139(4):1228-1241.
• Akinduro O et al., Constitutive Autophagy and Nucleophagy during Epidermal Differentiation. J Invest Dermatol. 2016 Jul;136(7):1460-70.
• Naeem AS et al., AKT1-mediated Lamin A/C degradation is required for nuclear degradation and normal epidermal terminal differentiation. Cell Death Differ. 2015 Dec;22(12):2123-32.
• Youssef G et al., Identifying a hyperkeratosis signature in autosomal recessive congenital ichthyosis: Mdm2 inhibition prevents hyperkeratosis in a rat ARCI model. J Invest Dermatol. 2014 Mar;134(3):858-61.
• Sully K et al., The mTOR inhibitor rapamycin opposes carcinogenic changes to epidermal Akt1/PKBα isoform signaling. Oncogene. 2013 Jul 4;32(27):3254-62.
• O'Shaughnessy RFL, Choudhary I, and Harper JI. Interleukin-1 alpha blockade prevents hyperkeratosis in an in vitro model of lamellar ichthyosis. Hum Mol Genet. 2010 Jul 1;19(13):2594-605.
• O'Shaughnessy RFL et al., Akt-dependent Pp2a activity is required for epidermal barrier formation during late embryonic development. Development. 2009 Oct;136(20):3423-31.
• O'Shaughnessy RFL, et al., Cutaneous human papillomaviruses down-regulate AKT1, whereas AKT2 up-regulation and activation associates with tumors. Cancer Res. 2007 Sep 1;67(17):8207-15.
• O'Shaughnessy RFL, et al., AKT-dependent HspB1 (Hsp27) activity in epidermal differentiation. J Biol Chem. 2007 Jun 8;282(23):17297-305.
• Kljuic A et al, Desmoglein 4 in hair follicle differentiation and epidermal adhesion: evidence from inherited hypotrichosis and acquired pemphigus vulgaris. Cell. 2003 Apr 18;113(2):249-60.

https://elements.qmul.ac.uk/userprofile.html?uid=20453

 Publication ID:ORCID 0000-0002-3701-0267

Supervision

Research Group Members:

• Clare Rogerson – Postdoctoral Research Associate
• Hephzi Tagoe – British Skin Foundation PhD Student
• Benjamin Way – Clinical Research Associate at UCL

http://www.qmul.ac.uk/blizard/staff/centre-for-cell-biology-and-cutaneous-research/items/ryan-oshaughnessy.html