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Early detection of colorectal cancer

  • Full or part time
  • Application Deadline
    Tuesday, November 12, 2019
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

This 4-year PhD studentship is offered in Dr Vivian Li’s Group based at the Francis Crick Institute (the Crick).

Wnt signalling pathway is genetically activated in nearly all colorectal cancer (CRC), yet there are significant challenges in targeting the Wnt pathway due to its pivotal role in stem cell function and tissue homeostasis of many body systems [1]. Our lab investigates how Wnt signalling is precisely controlled in intestinal stem cell and cancer, with the emphasis on finding new tumour-specific targets for therapeutic intervention and early detection.

Based on our previous work on Wnt signalling pathway [2], we have recently discovered a number of novel Wnt activating mechanisms in CRC [3, 4]. In particular, our discoveries on the deubiquitinating enzyme USP7 as tumour-specific drug target has brought significant impact to the therapeutic intervention of Wnt signalling in cancer [4]. We are currently exploring the link between Wnt activation and immunosuppression in CRC. Despite promising results of immunotherapies in the clinic, the response rate is very low in CRC [5]. We investigate the mechanism underlying the poor response rate of immunotherapy in CRC and with the aim to develop effective treatment.

Apart from therapeutic development, early diagnosis is another key parameter to prevent cancer progression and improve the survival rate of cancer patients. Since Wnt activation/Apc mutation is the earliest step of most CRC initiation, we are interested in identifying specific Wnt-mediated targets that can be used as early diagnostic markers. This project will involve transgenic mouse models, advanced sequencing, proteomics, organoid culture, imaging, primary human tissue samples etc. The candidate will be mainly involved in developing early detection strategies for CRC, but will also work closely with other colleagues in the lab and contribute to other related projects (such as immunotherapies).

Candidate background
We seek a highly talented and motivated student in the area of Wnt signalling and cancer to join Dr. Vivian Li’s laboratory.

This project would suit candidates with a background in cancer biology, and an interest in signalling mechanism and microbiome. The successful candidate is likely to be an ambitious, focused, and productive individual with a desire to work in a congenial, dynamic, and collaborative research environment. Good organisational, analytical, and communication skills are essential. Candidate with experience in organoid culture, mice handling, cancer immunology or microbiome will be advantageous.

Talented and motivated students passionate about doing research are invited to apply for this PhD position. The successful applicant will join the Crick PhD Programme in September 2020 and will register for their PhD at one of the Crick partner universities (Imperial College London, King’s College London or UCL).

Applicants should hold or expect to gain a first/upper second-class honours degree or equivalent in a relevant subject and have appropriate research experience as part of, or outside of, a university degree course and/or a Masters degree in a relevant subject.

APPLICATIONS MUST BE MADE ONLINE VIA OUR WEBSITE (ACCESSIBLE VIA THE ‘APPLY NOW’ LINK ABOVE) BY 12:00 (NOON) 13 NOVEMBER 2019. APPLICATIONS WILL NOT BE ACCEPTED IN ANY OTHER FORMAT.

Funding Notes

Successful applicants will be awarded a non-taxable annual stipend of £22,000 plus payment of university tuition fees. Students of all nationalities are eligible to apply.

References

1. Novellasdemunt, L., Antas, P. and Li, V. S. W. (2015)

Targeting Wnt signaling in colorectal cancer. A review in the theme: cell signaling: proteins, pathways and mechanisms.

American Journal of Physiology. Cell Physiology 309: C511-C521. PubMed abstract

2. Li, V. S. W., Ng, S. S., Boersema, P. J., Low, T. Y., Karthaus, W. R., Gerlach, J. P., . . . Clevers, H. (2012)

Wnt signaling through inhibition of β-catenin degradation in an intact Axin1 complex.

Cell 149: 1245-1256. PubMed abstract

3. Antas, P., Novellasdemunt, L., Kucharska, A., Massie, I., Carvalho, J., Oukrif, D., . . . Li, V. S. W. (2019)

SH3BP4 regulates intestinal stem cells and tumorigenesis by modulating β-catenin nuclear localization.

Cell Reports 26: 2266-2273 e2264. PubMed abstract

4. Novellasdemunt, L., Foglizzo, V., Cuadrado, L., Antas, P., Kucharska, A., Encheva, V., . . . Li, V. S. W. (2017)

USP7 is a tumor-specific WNT activator for APC-mutated colorectal cancer by mediating β-catenin deubiquitination.

Cell Reports 21: 612-627. PubMed abstract

5. Kalyan, A., Kircher, S., Shah, H., Mulcahy, M. and Benson, A. (2018)

Updates on immunotherapy for colorectal cancer.

Journal of Gastrointestinal Oncology 9: 160-169. PubMed abstract

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