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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 […]

Investigating Mechanisms of Tumor Dormancy in Adult Acute Lymphomblastic Leukemia Although many adults with ALL respond to initial treatment disease relapse occurs frequently. We think there are “dormant/non growing tumor cells which can resist chemotherapy to cause cancer recurrence. By working out how dormant cells remain “switched off” we may be able to reverse this […]

Closing the Knowledge Gap in Post-genomic Research: Fast-track Functional Characterisation of Genes Implicated in Human Blood Formation and Pathologies Using Zebrafish as an in vivo Model Dr. Ana Cvejic is hunting down genes involved in the development of leukaemia, by studying zebrafish. The processes taking place in zebrafish cells are remarkably similar to those in […]

Unravelling Clonal Complexity in Myelofibrosis Stem Cells Though [sic] Application of Single Cell Transcriptomics Not all blood cancer cells can cause disease relapse following treatment. Understanding the biology relapse-causing “cancer stem cells” is critical, but is akin to “finding a needle in a haystack.” This grant will support the development of single-cell genetics to better […]

Cytokine Signaling in Normal and Malignant Hematopoietic Stem/Progenitor Cells Dysregulation of signaling pathways that control hematopoietic stem cell expansion leads to leukemia. We aim to investigate novel signaling molecules for their roles in regulating stem cell expansion in normal and malignant blood development. Our studies may provide new insights into strategies to treat malignant and […]

Immunotherapy of Leukemia with Dendritic Cell-Tumor Hybrid Vaccines This research project will develop a new type of human leukemia vaccine using a novel electrofusion technology. Leukemia cells will be fused with the cells that regulate body immune system function to form a hybrid cell. The hybrid cells will carry tumor-derived information (proteins) to activate the […]

Tissue-specific immunity to preserve the graft-versus-tumor effect following hematopoietic cell transplantation Hematopoietic stem cell transplantation (HCT) can cure hematological cancers, but its wider use is limited by the high morbidity and mortality associated with graft-versus-host disease (GVHD). Current therapies for GVHD lead to nonspecific suppression or depletion of T cells, thus potentially compromising the ability […]

Integrative Epigenomics: The Consequences of Kdm6a Inactivation on Chromatin Accessibility and DNA Methylation in Hematopoiesis We will determine if mutations in the gene, KDM6A, which are present in a wide variety of human cancers, are also associated with specific modifications of DNA (DNA methylation) and DNA structure. These associated changes may explain how KDM6A mutations […]