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Cytokine Release Syndrome in Immunotherapy Most children with cancer can be cured by standard therapies yet some cancers will be resistant or will relapse. Recent therapies using modified immune cells have shown great promise, but also make patients very ill. I propose to investigate these modified immune cells in order reduce untoward side effects.

Defining the role and therapeutic potential of TNF receptor-associated factor 6 in Myelodysplastic Syndromes

Metabolic regulation of leukemia stem cells We will determine the role of AMPK in AML using mouse models and identify the key metabolic pathway regulated by AMPK that maintains AML-initiating cell population. Our goal is to understand how AML cells maintain metabolic integrity to develop new therapies targeting this common requirement of cancer.

Genetic Complexity of Quiescent Leukaemic Stem Cells Childhood acute lymphoblastic leukaemia (ALL) patients respond initially well to chemotherapy, but some relapse due to the proliferation of treatment-resistant dormant cells. We have demonstrated that leukaemia patients have different sub-clones, so no we aim to investigate which of these sub-clones contains dormant cells responsible for subsequent relapses.

Therapeutic targeting of cancer stem cells in mouse and human myelodysplastic syndromes Myelodysplastic syndromes is a hematologic malignancy driven by rare cancer stem cells defective in their ability to generate mature blood cells. Our goal is to identify drugable targets that can restore the cancer stem cells’ ability to generate functionally normal blood cells, thereby […]

Pathogenesis of Aggressive B Cell Lymphoma We seek to understand how the control systems of normal cells become corrupted during the process of lymphoma development. In doing so, we aim to identify cancerous pathways that can be inhibited by novel drugs in a way that specifically targets the cancerous cells while leaving normal cells intact.

Discovery and targeting of neomorphic enhancer mutations of oncogenes (NEMOs) in T-cell acute lymphoblastic leukaemia In acute lymphoblastic leukaemia, we recently discovered mutations in ‘junk DNA’ that can activate cancer-causing genes (oncogenes). Such mutations loosen up tightly knotted DNA, leading to activation of the nearby oncogene. We believe this is a common cause of leukaemia […]

Understanding reciprocal cell-cell interactions in B cell malignancies Indolent B cell lymphomas are incurable diseases with an increasing prevalence. Our work is aimed at understanding how malignant B cells communicate with normal cells, since interference with this cell-cell communication can be used to indirectly kill tumor cells, a new and alternative approach to cancer therapy.

The Evolution and Diversification of Pre-leukaemic Clones in a Natural Model of Acute Lymphoblastic Leukaemia We are interested in the development and evolution of the most common pre-B cell paediatric acute lymphoblastic leukaemia (ALL). We wish to study the similarities and differences in the mutations and sub-clones that develop in identical twins that share a […]

Development and Characterisation of a Mouse Model for Infant Leukaemia Infants with leukaemia caused by the MLL-AF4 mutation have a poor prognosis. MLL-AF4 alone failed to incite leukaemia in mouse models, impeding research into therapies. We will introduce the reciprocal fusion, AF4-MLL, alongside MLL-AF4 to produce a leukaemia mouse model for drug research to improve […]

Targeting the Secretory Apparatus in Multiple Myeloma Dr. Holger Auner is finding new ways to treat multiple myeloma. His research is focusing on a process called the protein degradation pathway that acts like a ‘waste disposal system’. Blocking this process in myeloma cells causes a toxic build-up of molecules which makes the cells self-destruct. Dr. […]

A Study of the Immunological Consequences of JAK inhibition in the Myeloproliferative Neoplasms MPNs are a type of cancer that can develop into leukaemia and cause serious blood clots. We believe that the immune system is not normal in MPN. An efficacious new treatment is available and we want to see what effect this treatment […]