Harnessing human skin knockout models to discover CYLD mediated protective homeostatic mechanisms in skin cancer and neurodegenerative disease

Principal Investigator: Dr Neil Rajan

Inherited skin tumour syndromes represent accelerated models of skin tumour formation, with multiple, early-onset tumours being a defining feature. This project will study inherited skin tumours from local genotyped cohorts of CYLD cutaneous syndrome (CCS) patients to better understand the role the CYLD gene plays in cell survival. CYLD is a tumour suppressor gene that is inactivated in these patients’ skin tumours as well as in a range of sporadic cancers including melanoma, liver cancer and leukaemia. In addition, some families with inherited early onset dementia have gain of function CYLD mutations, suggesting that increased activity of CYLD may reduce cell survival in neuronal tissues in the brain.

This pilot project will use single cell transcriptomics, to provide novel insights into the mechanisms used by CCS skin tumour cells for survival, relevant to developing therapeutics for CCS patients. In addition, these insights may be more broadly relevant to understanding reduced cell survival in the ageing brain of patients with CYLD associated early onset dementia.