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Morphostasis of the intestinal mucosa and it's deregulation in cancer and inflammation

Objective

Stem cells at the base of the intestinal crypts are in a dynamic equilibrium with their differentiated derivatives. Homeostatic equilibria depend on the presence of negative feedback loops. The role of the Wnt signaling pathway as a driver of epithelial stem cell self renewal and proliferation in the intestine has been relatively well characterized. Much less is known about the negative feedback signals that must exist to control stem cell behavior and the way these may be deregulated in disease. We found that Indian hedgehog is secreted by differentiated intestinal epithelial cells and acts as a negative feedback signal. Hedgehog signaling acts as a break on Wnt signaling in intestinal precursor cells via a secondary signal in the mesenchyme. We will use conditional mutant mice, our large biobank of patient materials and in vitro experiments to further characterize the signals involved in this feedback loop. Our objective is to study the role of this epithelial mesenchymal signaling circuit in the normal intestine and examine the way it is deregulated in intestinal cancer development and inflammation.

Field of science

  • /medical and health sciences/medical biotechnology/cells technologies/stem cells
  • /medical and health sciences/clinical medicine/oncology/cancer

Call for proposal

ERC-2009-StG
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
Address
Meibergdreef 15
1105AZ Amsterdam
Netherlands
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 275 102
Principal investigator
Gijs Van Den Brink (Dr.)
Administrative Contact
Edwin Groenewegen Van Wijk (Mr.)

Beneficiaries (2)

ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
Netherlands
EU contribution
€ 1 275 102
Address
Meibergdreef 15
1105AZ Amsterdam
Activity type
Higher or Secondary Education Establishments
Principal investigator
Gijs Van Den Brink (Dr.)
Administrative Contact
Edwin Groenewegen Van Wijk (Mr.)
ACADEMISCH ZIEKENHUIS LEIDEN

Participation ended

Netherlands
EU contribution
€ 249 360
Address
Albinusdreef 2
2333 ZA Leiden
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Esther Reinhard (Dr.)