Bone Morphogenetic Protein signalling and stromal-epithelial interaction in intestinal inflammation and carcinogenesis. (360G-Wellcome-206314_Z_17_Z)
The intestinal mucosa is a complex ecosystem and the epithelium has a dynamic relationship with underlying stroma. Key aspects of intestinal homeostasis and disease states, including inflammatory bowel disease and cancer are characterized by the interdependence of the epithelial and stromal compartments. Inter-compartmental cell-signalling pathways regulate intestinal epithelial cell fate determination in homeostasis, and transient perturbation of these networks is required in the physiological response to inflammation and injury. This promotes epithelial stem cell behaviour, cell proliferation and migration as part of a wound healing response. However, failure of restoration of homeostatic control in chronic inflammation, or pathological disruption of signalling can result in neoplasia initiation and progression. In resultant tumours, optimally selected somatic mutation spectra differ and reflect these variable influences on lesion pathogenesis. This proposal will explore these concepts using disruption in Bone Morphogenetic Protein signalling and it's pleiotrophic antagonist Gremlin1, as exemplars of the paradigm. Specific goals include: 1. Identifying stromal cell populations expressing Grem1 in intestinal regeneration and tumour desmoplasia. 2. Assess the functional role of BMP disruption in these conditions. 3. Using mouse models to test therapeutic manipulation of BMP signalling. 4. Using somatic mutation analysis to generate molecular biomarkers of Grem1 initiated tumourigenesis.
Where is this data from?
This data was originally published by The Wellcome Trust. If you see something about your organisation or the funding it has received on this page that doesn't look right you can submit a grantee amendment request. You can hover over codes from standard codelists to see the user-friendly name provided by 360Giving.
Grant Details
Amount Awarded | 1792405 |
Applicant Surname | Leedham |
Approval Committee | Science Interview Panel |
Award Date | 2017-04-05T00:00:00+00:00 |
Financial Year | 2016/17 |
Grant Programme: Title | Senior Research Fellowship Clinical |
Internal ID | 206314/Z/17/Z |
Lead Applicant | Prof Simon Leedham |
Partnership Value | 1792405 |
Planned Dates: End Date | 2023-07-01T00:00:00+00:00 |
Planned Dates: Start Date | 2018-01-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | South East |
Sponsor(s) | Prof Christopher Conlon, Prof Peter Donnelly |