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RUSHWORTHU18BC Investigating the role of the aging cancer microenvironment in the development of leukaemia


Project Description

There are more than 230,000 people living with blood cancer in the UK and 38,000 people are diagnosed with blood cancer each year. The three main groups are leukaemia, lymphoma and myeloma, but there are more than 130 individual types. Blood cancer is a malignant disorder characterized by accumulation of abnormal blood cells in bone marrow. Blood cancer is primarily a disease of the elderly. In younger patients (<65 years old), there is clear evidence of improved survival in the last two or three decades, however in the majority group of older patients, there is little evidence of similar improvement, and the appropriateness of intensive chemotherapy treatment represents a current dilemma. Accordingly, to improve outcomes for all patients (including older patients with blood cancer) there is a requirement for more effective treatments with reduced side effects.

This advertised project will advance our understanding of how the aging bone marrow environment promotes the survival and proliferation of abnormal blood cancer cells. We will investigate how leukaemia once established, promotes the aging environment in which to grow.
To do this work we will employ in vitro assays with primary human blood cancer cells from the clinic at the Norfolk and Norwich University Hospital to determine how the environment helps to promote the proliferation of leukaemia. We will then use in-vivo assays to confirm our in-vitro data. Together the data generated from this project will hopefully identify new therapeutic targets for these incurable diseases.


For more information on the supervisor for this project, please go here: https://people.uea.ac.uk/en/persons/s-rushworth

Type of programme: PhD

Project start date: October 2019

Mode of study: Full time

Entry requirements: Acceptable first Science related degree. The standard minimum entry requirement is 2:1

Funding Notes

This PhD studentship is funded by the Big C. Funding comprises Home/EU fees, an annual stipend of £14,777 and an RTSG of £1000 per year. Overseas applicants may apply but they are required to fund the difference between home/EU and overseas tuition fees (which for 2018-19 are detailed on the University’s fees pages at View Website . Please note tuition fees are subject to an annual increase).

References

1. CD38-driven mitochondrial trafficking promotes bioenergetic plasticity in multiple myeloma. Marlein CR, Piddock RE, Mistry JJ, Zaitseva L, Hellmich C, Horton RH, Zhou Z, Auger MJ, Bowles KM, Rushworth SA. Cancer Res. 2019 Jan 8

2. Acute myeloid leukemia induces pro-tumoral p16INK4a driven senescence in the bone marrow microenvironment. Abdul-Aziz, A. M., Sun, Y., Hellmich, C., Marlein, C. R., Mistry, J., Forde, E., Piddock, R. E., Shafat, M. S., Morfakis, A., Mehta, T., Di Palma, F., Macaulay, I., Ingham, C. J., Haestier, A., Collins, A., Campisi, J., Bowles, K. M. & Rushworth, S. A. 6 Nov 2018 In : Blood

3. NADPH oxidase-2 derived superoxide drives mitochondrial transfer from bone marrow stromal cells to leukemic blasts. Marlein CR, Zaitseva L, Piddock RE, Robinson SD, Edwards DR, Shafat MS, Zhou Z, Lawes M, Bowles KM, Rushworth SA. Blood. 2017 Oct 5;130(14):1649-1660

4. The bone marrow microenvironment - Home of the leukemic blasts. Shafat MS, Gnaneswaran B, Bowles KM, Rushworth SA. Blood Rev. 2017 Sep;31(5):277-286. doi:

5. Leukemic blasts program bone marrow adipocytes to generate a protumoral microenvironment. Shafat MS, Oellerich T, Mohr S, Robinson SD, Edwards DR, Marlein CR, Piddock RE, Fenech M, Zaitseva L, Abdul-Aziz A, Turner J, Watkins JA, Lawes M, Bowles KM, Rushworth SA. Blood. 2017 Mar 9;129(10):1320-1332

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