Key Research Interests and Expertise

I am a physiologist interested in the cellular and molecular mechanisms that govern the self-renewal and physiological function of the human intestinal epithelium. A major focus of our work is to understand how age-related molecular damage and inherited genetic defects pre-dispose the intestinal epithelium to the onset of gastrointestinal disease. The ethos of our work is to conduct comparative studies on human tissue samples derived from young and old healthy subjects, and from patients with inflammatory bowel disease and cancer. To this end, our laboratory has developed an ex vivo culture model of the human intestinal epithelium that is amenable to bio-imaging and the investigation of cellular signals for crypt cell proliferation, migration, differentiation and secretion.

Current Research Projects

  • Signalling self-renewal in the human intestinal epithelium ex vivo (Collaboration with Dr Munsterberg, BIO, UEA)
  • Epigenetic modulation of Wnt signalling in the ageing human intestinal epithelium: consequences for tissue homeostasis (Collaboration with Dr Nigel Belshaw and Prof. Ian Johnson at the Institute of Food Research).
  • Wnt signaling pathways in colon cancer initiation
  • Molecular regulation of intestinal fluid secretion in health and disease.
  • Inflammatory signals for Barrett’s oesophagus (Collaboration with Mike Lewis, Norfolk and Norwich University Hospital)

 

Life in our research group 

Bio-imaging and functional genomic approaches are applied to a3D ex vivo culture model of the human colonic epithelium, which was developed in collaboration with clinicians at the Norfolk and Norwich University Hospital. The cellular and molecular mechanisms governing adult tissue homeostasis in health and disease are interrogated by utilising recombinant/pharmacological activators/inhibitors, RNAi and GFP transgenes, in combination with bright field / fluorescence time-lapse imaging and immunocytochemistry/in situ hyrbridisation. Regulation of stem cell-driven tissue renewal by Wnt signals and the mechanisms of fluid transport across the polarised intestinal epithelium are of particular interest. In a broader context, the cultured colonic crypt also serves as a model for other self-renewing tissues and polarised epithelia. Although laboratory life is somewhat crypt-centric, the resident cryptomaniacs are let out on occasion to partake in social activities such as sailing, ice-skating, dancing, BBQs and dining, a favourite restaurant being ... the Crypt!

PhD Positions 

Click here for current PhD opportunities in Biological Sciences. But feel free to email me to discuss projects outside these areas and alternative sources of funding.

Postdocs & Fellows 

I am always happy to discuss possibilities for postdoctoral work and collaborations. Possible funding routes include applying for fellowships, e.g. EU Marie Curie fellowships, Royal Society and others, or grant applications with you as a named post-doc.

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