Coventry University Featured PhD Programmes
University of Warwick Featured PhD Programmes
Coventry University Featured PhD Programmes

Investigating differentiation processes in normal and tumoral cells which affect phenotypic heterogeneity and stemness.


Division of Cancer and Stem Cells

Nottingham United Kingdom Biochemistry Bioinformatics Biophysics Cancer Biology Cell Biology Genetics Microbiology

About the Project

Our research is focused on understanding tissue renewal in health and disease using the intestine as a model system to study adult stem cell biology for a therapeutic benefit. (Ordóñez-Morán et al., Cancer Cell, Gjorevski et al., Nature). The intestinal epithelium is the most rapidly self-renewing tissue in mammals and its vigorous regeneration is enabled by highly active intestinal stem cells. We have recently described that differentiating cancer stem cells inhibits colorectal cancer progression (Ordóñez-Morán et al., Cancer Cell).

Cancer is one of the leading causes of death world-wide therefore there is an urgent need for more fruitful treatments for cancer patients. At advanced stages of disease, conventional therapies are ineffective due to a small population of drug-resistant cells called cancer stem cells that can reform the tumour. Indeed, the spread of these cells to distant organs accounts for over 90% of patient deaths. Our aim is to discover how these resistant cells can be efficiently and permanently eliminated. Thus, our research is focused on the novel regulatory mechanisms which govern the balance between stem cell maintenance and differentiation. Furthermore, by disentangling the heterogeneity within the tumour, we aim to identify the key players and properties that enable stem cells to cause cancer growth and spreading. We will also study the mechanisms involved in cell plasticity to understand how cancer cells respond to conventional therapies depending on their state. To this end, we will use mouse models, clinical association analyses, high-throughput approaches, next-generation sequencing, single cell technologies, patient-derived material and 3D organoids which very well models intra-tumour heterogeneity.

Our main goals are:

·      Characterize the cells that are resistant to current therapies.

  • Force cancer cells to change their properties (lose their stemness becoming differentiated cells) so that they can no longer divide and reform a tumour.
  • Understand the reversibility of the stemness process (as differentiated cells can also gain stem cell properties). It will help us to design trials to overcome resistance.
  • Study how these resistant cells can be targeted by novel approaches or drug combinations.

By tackling the above-mentioned research goals, we hope to improve treatment of cancer by:

·    Identifying patients that are likely to relapse and/or stop responding to the treatment.

·    Reduce the number of possible therapeutic strategies.

·    Design novel drug combinations to increase rates of response and cure through more precise use of cancer therapies.

·    Improve patient’s survival.

Please include in your application:

·      A detailed CV;

·      Names and addresses of three referees;

·      A covering letter highlighting your research experience/capabilities;

·      At the top of your letter please put the name of your proposed supervisor and the title of the research


Funding Notes

We will consider applications from self-funded prospective students with:
• a good biomedical or related degree, with interests in any of the areas outlined above,
• a good command of the English language (written and spoken) as outlined in the postgraduate prospectus,
• competence with computers and data handling,
• a source of funding to cover tuition fees and bench fees (note that tuition fees are different for Home and EU students than for International students). More information regarding fees can be found under the ‘Medicine’ heading at: View Website
To be considered for this studentship, please apply online at: View Website

References

Gjorevski N, Sachs N, Manfrin A, Giger S, Bragina M, Ordóñez-Morán P*, Clevers H, Lutolf M. Designer matrices for intestinal stem cell and organoid culture. Nature 2016, Nov 24, 560-564 (* signed as independent researcher).
Ordóñez-Morán P, Dafflon C, Imajo M, Nishida E, Huelsken J. HOXA5 counteracts stem cell traits by inhibiting Wnt signaling in colorectal cancer. Cancer Cell 2015, Dec 14, 815-829.

Email Now

Insert previous message below for editing? 
You haven’t included a message. Providing a specific message means universities will take your enquiry more seriously and helps them provide the information you need.
Why not add a message here

The information you submit to University of Nottingham will only be used by them or their data partners to deal with your enquiry, according to their privacy notice. For more information on how we use and store your data, please read our privacy statement.

* required field

Your enquiry has been emailed successfully



Search Suggestions

Search Suggestions

Based on your current searches we recommend the following search filters.



FindAPhD. Copyright 2005-2021
All rights reserved.