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Cambridge, United Kingdom

Roshan A.,University of Cambridge | Jones P.H.,MRC Cancer Cell Unit
Seminars in Cell and Developmental Biology | Year: 2012

In all tissues the balance of cell proliferation and differentiation needs to be tuned to match the varying requirements of embryonic development and adult life. This is well illustrated by the interfollicular epidermis (IFE), which undergoes expansion and remodeling in utero, significant post natal growth and is then maintained in homeostasis. In addition to sustaining a high daily turnover of cells, the epidermis is able to re-populate areas of tissue damage due to common environmental stresses such as wounding. Here recent insights into proliferating cell behavior in IFE and how this changes through development and into adulthood are discussed. © 2012 Elsevier Ltd.


Doupe D.P.,University of Cambridge | Jones P.H.,MRC Cancer Cell Unit
BioEssays | Year: 2013

It has recently been shown that stem and progenitor cells undergo population self-renewal to maintain epithelial homeostasis. The fate of individual cells is stochastic but the production of proliferating and differentiating cells is balanced across the population. This new paradigm, originating in mouse epidermis and since extended to mouse oesophagus and mouse and Drosophila intestine, is in contrast to the long held model of epithelial maintenance by exclusively asymmetric division of stem cells. Recent lineage tracing studies have now shown that wound responses vary between tissues, and that a stem cell reserve is not essential as cycling progenitors and even differentiating cells contribute to regeneration. © 2013 WILEY Periodicals, Inc.


Spechler S.J.,University of Texas Southwestern Medical Center | Fitzgerald R.C.,MRC Cancer Cell Unit | Prasad G.A.,Rochester College | Wang K.K.,Rochester College
Gastroenterology | Year: 2010

This report is an adjunct to the American Gastroenterological Association Institute's medical position statement and technical review on the management of Barrett's esophagus, which will be published in the near future. Those documents will consider a number of broad questions on the diagnosis, clinical features, and management of patients with Barrett's esophagus, and the reader is referred to the technical review for an in-depth discussion of those topics. In this report, we review historical, molecular, and endoscopic therapeutic aspects of Barrett's esophagus that are of interest to clinicians and researchers. © 2010 AGA Institute.


Grant
Agency: GTR | Branch: MRC | Program: | Phase: Intramural | Award Amount: 571.67K | Year: 2011

There is much excitement about using our immune system to fight cancer instead of toxic drugs. Although successful in the laboratory, transition to the clinic is proving more difficult. These problems likely arise because tumours create a protective microenvironment, to which our immune system is ineffective. Non-cancerous cells in the tumour form a supportive network known as the tumour stroma. We do not yet fully understand how the stroma promotes tumour development, or how it contributes to the related immune dysfunction. Tumours induce the growth of lymphatic vessels within the stroma. There, lymphatics drain fluid from the tumour, but also act as the route by which tumour cells spread. Additionally, lymphatics connect a tumour to our immune system. So, how, although connected to our defences, can a tumour evade immune destruction? We believe that rather than simply providing structural support to a developing tumour, the stroma has a much more active role in establishing the protective microenvironment and ultimately making a tumour more difficult to treat. Our research uses state of the art in vitro and in vivo systems to determine how the stroma, the cells it interacts with, and the physical forces experienced by these, impact tumour development; and ultimately, how we can exploit these feature to more effectively treat cancer.


Alcolea M.P.,MRC Cancer Cell Unit | Jones P.H.,MRC Cancer Cell Unit
Nature Reviews Cancer | Year: 2013

For tumours to develop, mutations must disrupt tissue homeostasis in favour of deregulated proliferation. Genetic lineage tracing has uncovered the behaviour of proliferating cells that underpins the maintenance of epithelial tissues and the barriers that are broken in neoplastic transformation. In this Review, we focus on new insights revealed by quantifying the behaviour of normal, preneoplastic and tumour cells in epithelia in transgenic mice and consider their potential importance in humans.© 2013 Macmillan Publishers Limited. All rights reserved.

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