2014 Funding Round – Project

Professor Anthony Braithwaite
University of Otago, Dunedin
A role for p53 isoforms in inflammatory disease
36 months

Lay summary

We investigate a role for oncoprotein p53 variants, especially  133p53, in the development of autoimmune disease. The work is based on our transgenic mouse expressing an analogue of  133p53 (designated  122p53), which develops features of autoimmune disease by modulation of pro-inflammatory genes. We will characterize inflammatory pathologies of the mice and investigate a role for the cytokine IL-6 and the STAT-1/interferon pathway as 'driving' autoimmune disease, using  122p53 mice that lack the IL-6 or STAT-1 genes. To translate these findings to man, we will analyse Rheumatoid Arthritis joint tissue for  133p53 expression, relate that to pathology and inflammatory gene transcripts and quantitate the levels of other p53 isoforms and novel variants to determine if they are associated with inflammatory disease. We will interrogate publically available RA transcript databases for similar associations using bioinformatics. The outcome of our experiments will be to define the role p53 isoforms play in autoimmune disease.

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