Award details

Challenging dogma: an alternative non-hierarchical, epigenetically regulated model of the urothelium.

Reference	BB/R009295/2
Principal Investigator / Supervisor	Dr Andrew Feber
Co-Investigators / Co-Supervisors
Institution	Institute of Cancer Research
Department	Division of Molecular Pathology
Funding type	Research
Value (£)	91,149
Status	Completed
Type	Research Grant
Start date	01/08/2020
End date	09/01/2022
Duration	17 months

Abstract

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Summary

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Impact Summary

Who could adopt or benefit from the research? The immediate beneficiaries of our research will be the academic community but, in the long term, it is the public who will benefit from our research, which we recognise will need industry engagement to help with translation. Urinary incontinence is a major problem associated with ageing and there are numerous, poorly understood chronic age-associated conditions affecting the urinary bladder where a better understanding of the basic biology of the tissue and how it is regulated will revolutionise treatment. These conditions not only affect quality of life, but have a significant negative impact on society and the economy. How will they benefit? The results of this basic biology project will provide important insight that could help develop better cell and tissue engineering solutions as well as opening doors to rejuvenation therapies using epigenetic modulators: 1) The existence or not of a hierarchical stem cell is important for understanding whether the stem cell should be the primary target for therapies. This includes not only cancer, but poorly-understood chronic benign inflammatory conditions, such as interstitial cystitis, wherein there is an underlying failure of urothelial homeostasis. 2) there is a recognised need for new "tissue-engineered" approaches for patients with end-stage bladder disease. The results of the project will help inform strategy, such as whether to selected particular cell sub-population(s), or how to direct differentiation of induced pluripotent stem cells for therapeutic use. 3) Discovering how urothelial cell phenotypes are epigenetically-regulated will enable us to understand how environmental epigenetic modifiers compromise urothelial health (eg by disrupting plasticity) and how to reverse this by therapy. This could impact on environmental and health & safety practices. 4) in seeking regenerative therapies aimed at the chronic diseases of ageing, it is possible that epi-modifiers or epi-modulators could be used to "re-set" the epigenetic state of a diseased urothelium to re-establish normal homeostasis and regeneration. The project is likely to generate knowledge and materials of interest to industry involved in delivering a) research tools to the life sciences and b) translation of regenerative medicine through to patient benefit. JS has substantial pharma industry contacts (including Astellas, Ono) with whom the potential of any research findings would be discussed under confidentiality agreement. Such an approach in the past has resulted in industry-funded research contracts and collaborations (eg through CASE studentships). Our tangible objective will be to actively engage with industry to generate a minimum of one CASE studentship or piece of contract research with industry directly from this research.

Committee	Research Committee C (Genes, development and STEM approaches to biology)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

Associated awards:

BB/R006172/1 Challenging dogma: an alternative non-hierarchical, epigenetically regulated model of the urothelium.

BB/R009295/1 Challenging dogma: an alternative non-hierarchical, epigenetically regulated model of the urothelium.

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