PhD Studentship: Investigating the Metabolic Link Between Leukaemia and Heart Failure

Dr Stuart Rushworth

This 4-year PhD project funded by the Big C cancer charity represents an exciting opportunity to develop and conduct research at the forefront of cancer research.

Acute myeloid leukaemia (AML) is a highly lethal disease in which the overall survival rate has not improved over the last 25 years. It is now estimated that 20-30% of patients with cancer die due to cardiovascular causes, irrespective of the time passed after cancer diagnosis. Analysis of cancer types has shown that the highest rate of heart failure and cardiac death occurs in patients with hematologic malignancies, and specifically AML. To date, the strongest mechanistic link between cancer and heart failure has been through common metabolic abnormalities, which will be the focus of this project.

To gain a better understanding of the mechanisms regulating AML associated heart failure the student will use a combination of models. To do this, the PhD student will learn in vivo techniques including animal handling, as well as isolation of primary cells for functional characterisation. Additionally, the student will receive training in induced pluripotent stem cells (iPSC) models as well as cellular biology methodologies including, analysis of nucleic acids by qPCR and proteins by western blot, ELISA and immunohistochemistry. The student will also learn to characterise and isolate AML by FACS.

The project will be carried out under the supervision of Dr Rushworth and Dr James Smith (Norwich Medical School). We have successfully supervised 11 PhD students who immediately left for post-docs. Our labs are a supportive and collaborative environment, holds weekly lab meetings, biweekly journal club and encourages presentation at local, national and international meetings. Training provided will lead to the development of advanced research skills as well as other generic transferable skills.

Entry requirements

The minimum entry requirement is 2:1 in Biological Sciences or equivalent.

References

Perlecan (HSPG2) promotes structural, contractile, and metabolic development of human cardiomyocytes. Johnson BB, Cosson MV, Tsansizi LI, Holmes TL, Gilmore T, Hampton K, Song OR, Vo NTN, Nasir A, Chabronova A, Denning C, Peffers MJ, Merry CLR, Whitelock J, Troeberg L, Rushworth SA, Bernardo AS, Smith JGW.Cell Rep. 2024 Jan 23;43(1):113668

LC3-associated phagocytosis in bone marrow macrophages suppresses acute myeloid leukemia progression through STING activation. Moore JA, Mistry JJ, Hellmich C, Horton RH, Wojtowicz EE, Jibril A, Jefferson M, Wileman T, Beraza N, Bowles KM, Rushworth SA. J Clin Invest. 2022 Mar 1;132(5):e153157.

Free fatty-acid transport via CD36 drives β-oxidation-mediated hematopoietic stem cell response to infection. Mistry JJ, Hellmich C, Moore JA, Jibril A, Macaulay I, Moreno-Gonzalez M, Di Palma F, Beraza N, Bowles KM, Rushworth SA. Nat Commun. 2021 Dec 8;12(1):7130.

ROS-mediated PI3K activation drives mitochondrial transfer from stromal cells to hematopoietic stem cells in response to infection. Mistry JJ, Marlein CR, Moore JA, Hellmich C, Wojtowicz EE, Smith JGW, Macaulay I, Sun Y, Morfakis A, Patterson A, Horton RH, Divekar D, Morris CJ, Haestier A, Di Palma F, Beraza N, Bowles KM, Rushworth SA. Proc Natl Acad Sci U S A. 2019 Dec 3;116(49):24610-24619

Additional Funding Information

This is a fully funded studentship which covers tuition fees at Home fee rate and provides an annual stipend of £19,162 and £1,000 per annum to support research training.

Advert information