John Goldman Fellows 2015

Dr Sarah Nurmohamed

Dr Salima (Sarah) Nurmohamed, University of Oxford

Project Title: Characterisation of GATA2 in blood development and leukaemia

Summary:

The GATA2 protein helps regulate blood cell development and has two main functions: it binds DNA to switch genes on or off, and can simultaneously associate with other proteins to regulate genes. If either of these functions are disrupted, it can alter the development of blood cells in the body. Many mutations of the GATA2 protein have been identified, but it is still not known how these errors cause leukaemia.

Dr Nurmohamed’s work aims to decipher the mechanism of the GATA2 protein in normal blood development and explain how these GATA2 mutations cause Acute Myeloid Leukaemia. From the results of this research, we hope to progress the design and development of new and improved treatments.

 

 Dr Beth PayneDr Beth Payne, Cancer Institute, University of Central London

Project Title: Using in vivo small molecule screens to develop novel therapeutics for MDS5q

Summary:
Myelodysplastic syndrome (MDS) is a blood cancer that usually begins with symptoms of anaemia (low numbers of red blood cells). This can progress over time to a more severe illness and eventually leukaemia. Most patients with MDS die from leukaemia or infections as a result of the disease. The only curative treatment for MDS is a bone marrow transplant. However, bone marrow transplants require a suitable donor and are often associated with severe side effects and makes bone marrow transplants unsuitable treatments for many patients.

Dr Payne’s research aims to uncover new treatments that will be effective at improving symptoms and prolonging survival, with the ultimate goal of curing patients with MDS.

 

 Dr Vignir HelgasonDr G Vignir Helgason, Wolfson Wohl Cancer Research Centre, University of Glasgow

Project Title: Autophagy-Dependent Regulation of Energy Metabolism in Leukaemic Stem Cells

Summary:

The identification of Leukaemic Stem Cells (LSCs) in the late 1990s supported the idea that leukaemia is primarily drive by the presence of a collection of rare cancer stem cells in the blood.

This was an important development in the fight against leukaemia, as many anti-leukaemia treatments are evaluated on their ability to reduce the number of leukaemia cells. However, if the treatments are not killing LSCs, then the cancerous cells may develop drug resistance with time, causing a relapse and, ultimately, death.

Chronic Myeloid Leukaemia patients are currently treated with drugs called Tyrosine Kinase Inhibitors (TKIs) that inhibit the function of the cancer-causing protein BCR-ABL.

However, we have recently shown that CML LSCs can survive TKI treatment, indicating that this therapy alone will not lead to a cure. A combination of treatments is therefore required to cure Chronic Myeloid Leukaemia patients. Dr Helgason’s research will investigate vulnerabilities in CML LSCs and aim to identify new treatments for the eradication of CML LSCs.

 

 Dr Lisa RussellDr Lisa J Russell, Northern Institute for Cancer Research, Newcastle University

Project Title: Characterisation of a novel gene fusion in acute lymphoblastic leukaemia

Summary:
Dr Russell’s team have identified a new genetic abnormality present in patients with Acute Lymphoblastic Leukaemia. Genetic material is lost between two genes on chromosome X, which leads to them becoming fused together. Dr Russell and her team plan to investigate the effects of this fusion event.

They are interested in these genes and whether this is altered due to the fusion event and plan to design a simple test that could be used in the clinic to identify this fusion quickly and cost effectively.

They also plan to create this fusion in human cells and investigate the effects on cell growth and cell death. We hope to identify important signals in the cells affected by this fusion, which could identify new targets and which could be susceptible to new treatments and therapies.

 

 Dr Fernando AfonsoDr Fernando dos Anjos Afonso, European Cancer Stem Cell Research Institute, Cardiff

Project Title: Exploring the roles of canonical and non-canonical Notch signalling to target human acute myeloid leukaemia

Summary:
Blood stem cells are responsible for the growth and maintenance of all mature cells in our blood. Most of the current treatments for one type of leukaemia, named Acute Myeloid Leukaemia or AML, are very toxic and not very specific (targeting many cell types, including healthy blood stem cells). As a result, many patients cannot tolerate current available treatments.

If we can better understand the differences between the blood stem cells and the cells that drive the formation of the cancer, we can go on to create unique and powerful treatments.

Indeed, one of the mechanisms, the “Notch Pathway”, regulates blood stem cell maintenance but is detrimental for cells that drive AML formation. Dr Afonso’s research aims to understand how AML avoids the “Notch pathway”, thereby preventing the cancer cells from dying. By understanding these mechanisms, Dr Afonso’s team can begin to target AML with treatments.