About us
Research Focus
The primary focus of our research program is to better understand how genes that drive blood and mesenchymal stem cell development are regulated.
Our research is in the following core areas:
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Investigating transcription factor interactions that drive haematopoietic stem cell (HSC) and mesenchymal stem cells (MSC) development, self-renewal and differentiation
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Investigating interactions between the core transcription factor networks in HSCs and MSCs with cell signalling pathways associated with their development and maintenance
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Investigating links between the transcription factor network in embryonic HSCs and in leukaemic cells
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Investigating the pathogenesis of myelodysplasia (MDS) with a view to drug development
Research Interests
Interactions between Transcription Factor Networks and Cell Signaling Pathways during Early Blood Development
We have shown that the expression of Gata2, Fli1 and Scl genes are dramatically upregulated in mesodermal haematopoietic progenitors and form a cross regulating protein-DNA regulatory sub-circuit. Following its activation, this sub-circuit is predicted to maintain expression of each of the component transcription factors without need for a continuous extracellular stimulus. Therefore sufficient concentrations of these transcription factors, all of which are critical for normal haematopoiesis, can be maintained in haematopoietic stem cells so that they can regulate downstream target genes. Bmp4 is a likely stimulus that initiates Gata2 and Fli1 expression which we predict would be sufficient to activate the circuit. Our aim is to integrate the Gata2/Fli1/Scl sub-circuit with known mediators and master regulators of haematopoiesis. In particular, investigate whether the Gata2/Fli1/Scl gene regulatory network kernel regulates expression of mediators of the Bmp signalling pathway.
Tissue specific regulation of gene expression
To understand how tissues develop in the embryo, it is of fundamental importance to know how tissues switch on and off genes that are required for their biological identity and function. Promoter driven basal rates of gene expression are generally insufficient for mammalian development. Transcription factors bind distal enhancers and corporate with promoter complexes to boost the activity of the basal transcriptional machinery. A question that has not been adequately addressed is whether different tissues use distinct enhancers to regulate expression of the same gene and how expression is fine-tuned to suit individual needs. Our aim is to determine whether different cell types use distinct enhancers to regulate expression of the same gene. We will analyze sequence motifs within these tissue specific enhancers to build computational algorithms that will allow genome-wide prediction of gene regulatory elements that target blood, endothelial and mesenchymal progenitors.
Clinical database and biorepository for Myelodysplastic and Myeloproliferative disorders
A specialist haematology clinic will be established at the Prince of Wales Hospital for the investigation, management and prospective study of patients with myeloproliferative and myelodysplastic syndromes.
Team
People related to this group
Projects
Projects related to this group
Collaborators
Collaborators related to this group
Dr Brian Huntly, Cambridge University
Grants & Funding
Grants
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Project
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Source
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Duration
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Funding
|
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Epigenetic therapy in Myelodysplasia and Chronic Myelomonocytic Leukaemia (CIA)
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NHMRC |
2012-2014 |
$656,175 |
|
Drug Resistance in Paediatric Leukaemia (CIB)
|
NHMRC |
2012-2014 |
$450,000 |
|
Tissue specific regulation of gene expression (CIA)
|
ARC
|
2009-2011
|
$278,000
|
|
Transcriptional regulation of haematopoietic stem cell development (CIA)
|
NHMRC
|
2008-2010
|
$544,000
|
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Interactions between transcription factor networks and cell signalling pathways (CIA)
|
NHMRC
|
2009-2011
|
$566,500
|
|
Dissecting the embryonic blood-endothelial regulatory code and
investigating its role in leukaemia (CIA)
|
NHMRC
|
2010-2012
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$623,500
|
|
Determining the transcriptional program of a leukaemogenic
transcription factor in normal and leukaemic cells (CIA)
|
NHMRC
|
2011-2013
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$621,732
|
|
Upregulation of Dyskerin augments telomerase activity in
haematopoietic cells (CIB)
|
NHMRC
|
2011-2013
|
$359,208
|
|
Do Leukaemic cells use stem cell enhancers to express
oncogenic transcription factors? (CIA)
|
Leukaemia Foundation
|
2010
|
$98,000
|
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Pathogenesis of Myelodysplasia (CIA)
|
Leukaemia Foundation
|
2009-2011
|
$150,000
|
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Epigenetic changes associated with pharmacotherapy in
Myelodysplasia (CIA)
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Cancer Institute of NSW
|
2010
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$50,000
|
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Identifying transcriptional regulatory complexes in leukaemia (CIB)
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Cancer Institute of NSW
|
2011
|
$50,000
|
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Major Equipment Grant (CIA)
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UNSW/NHMRC
|
2010
|
$338,000
|
|
Major Equipment Grant (CIA)
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UNSW/NHMRC
|
2011
|
$142,000
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Research conducted by Stem Cell Group is being sponsored by the following agencies:
