SOX2 and squamous lung cancer (360G-Wellcome-097143_Z_11_Z)

£875,280

In the UK, squamous lung cancer (SQC) accounts for approximately 40% of cases. There is accumulating evidence that SOX2 may play a driving role in this common disease. This proposal will test the hypothesis that dysregulated expression of SOX2 is a critical event in the initiation and maintenance of squamous lung cancer (SQC). My aims are: 1. To establish the molecular context in which SOX2 dysregulation occurs in the pathogenesis of SQC. I have developed a unique, single molecule digital PCR protocol to facilitate a comprehensive and parallel survey of somatic copy-number variation and sequence mutations in microdissected archived precancer lesions. 2. To establish the effect of SOX2 dysregulation in an organotypic model of bronchial dysplasia. I will establish a 3-Dimensional organotypic model of bronchial dysplasia in which SOX2 overexpression can be reversibly activated, and the effect of this and potentially co-operating genetic lesions can be interrogated. 3. To develop a novel mouse model of SQC based on SOX2 dysregulation targeted to the basal stem cells of the adult mouse trachea. This state-of-the-art genetically engineered mouse will feature the ability to reversibly and sporadically activate SOX2 in the most plausible cell of origin of squamous lung cancer.

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Grant Details

Amount Awarded 875280
Applicant Surname McCaughan
Approval Committee Clinical Interview Committee
Award Date 2011-12-08T00:00:00+00:00
Financial Year 2011/12
Grant Programme: Title Intermediate Clinical Fellowship
Internal ID 097143/Z/11/Z
Lead Applicant Dr Frank McCaughan
Partnership Value 875280
Planned Dates: End Date 2017-05-01T00:00:00+00:00
Planned Dates: Start Date 2012-05-02T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Sponsor(s) Prof Gerard Evan