The Molecular Mechanisms in Leukaemia laboratory is located at the Adult Cancer Program at the Lowy Cancer Research Centre, UNSW in Sydney, Australia. Using our interdisciplinary backgrounds in epigenetics, cancer cell biology, transcriptomics, molecular biology and bioinformatics, we study the molecular processes that malfunction in leukemia.
Our goals
The overarching goals of our group are to discover the molecular pathways that transform healthy haematopoietic stem cells into leukaemic cells, and to identify the molecular causes underlying treatment resistance. In doing so, we believe we can discover new therapeutic targets and ultimately, improve the treatment of leukaemia.
Investigating the role of RNA splicing alterations in leukaemia
We are studying how alterations in RNA splicing, a fundamental biological mechanism that occurs in all human cells and affects ~95% of genes, might be a driver of leukaemia.
We have recently discovered that leukaemic cells have distinct and aberrant patterns of RNA splicing, though the molecular reasons underlying them remain unknown. We combine traditional wet-lab experimental techniques with “dry-lab” informatics approaches to answer our research questions.
In addition, we have begun investigating how aberrant RNA splicing might be involved in a range of cancers, beyond leukaemia, in collaboration with colleagues in other fields.
Understanding the molecular drivers of treatment resistance
We are interested in discovering the molecular pathways that contribute to treatment resistance in leukaemia. We have identified molecular pathways underlying treatment resistance to epigenetic therapy in Myelodysplastic Sydnrome (MDS), which has subsequently led to two clinical trials in MDS (including NCT03493646), based in Australia.
Research strengths
We have expertise in:
- cancer cell biology
- cancer stem cells
- genomics, transcriptomics, epigenomics
- RNA biology
- molecular biology
- proteomics and mass spectrometry
- bioinformatics.
We work with colleagues from a wide variety of disciplines, including computer science, materials sciences and chemistry.
Our results
We, along with our collaborators, have made recent discoveries on understanding RNA splicing, including its alteration in leukaemia:
- Discovery of RNA splicing alterations in Acute Myeloid Leukaemia
- Identification of the role of the RNA binding factor, RBM17, in leukaemia
- Studying RNA splicing patterns in healthy tissues
- Understanding the role of SRSF2 mutations in MDS
We also have a long-standing interest in deciphering the drivers of haematopoietic cancers as well as the factors underlying therapy resistance in leukaemia:
- Identifying the basis of resistance to Azacitidine therapy in MDS
- Development of the AZA-MS method to study intracellular dynamics of Azacitidine therapy
- Developing the reverse-ChIP method to identify transcriptional regulators in leukaemic cells
- Identifying ERV-derived neoantigens in MDS patients
- Detecting neoantigen-reactive T-cells in MDS
A full list of our publications can be found here
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