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STAFF
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Laboratory Head
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Associate Professor Richard D'Andrea
Ph: 08 8222 3626
Email: richard.dandrea@imvs.sa.gov.au |
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Research Staff
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Anna Brown |
anna.brown@imvs.sa.gov.au |
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Carolyn Butcher |
carolyn.butcher@imvs.sa.gov.au |
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Martina Ehlers |
martina.ehlers@imvs.sa.gov.au |
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Michelle Perugini |
michelle.perugini@imvs.sa.gov.au |
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Diana Salerno |
diana.salerno@imvs.sa.gov.au |
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Antiopi Varelias |
antiopi.varelias@adelaide.edu.au |
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Students
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Subhobrata Das |
subhobrata.das@student.adelaide.edu.au |
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Sonya Diakiw |
sonya.diakiw@student.adelaide.edu.au |
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Chung Kok |
chung.kok@adelaide.edu.au |
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Stephen Perderson |
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GOALS
To further understand the mechanisms underlying normal blood
cell growth, differentiation and leukaemia. In particular
we have focused on:
Understanding receptor signalling pathways and genetic mechanisms
that control normal myeloid cell growth and differentiation.
Identifying genetic and biochemical changes associated with
myeloid leukaemia.
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RESEARCH PROJECTS
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1. Cytokine Receptor signalling
As a strategy to identify key targets in myeloid leukemia
we examined the signaling and downstream events induced by
several activated receptor mutants associated with AML. We
focused on the events induced by activating mutations in the
FLT3 receptor, which is commonly mutated in AML, and a leukaemic
mutant of the GM-CSF receptor. We have:
Characterised the signaling events that are central to
the ability of both mutant receptors to induce changes associated
with leukaemia.
Shown that the overlapping nature of signalling by these
activated mutants is also evident in the induced gene expression
changes.
Identified down-regulation of the tumour suppressor gene,
Gadd45?, as a common and important response to signalling
via these activated receptors, and in AML.
Shown that Gadd45 expression reduces growth of AML cells.
We are continuing our investigations into these key pathways
and regulatory genes as these studies may identify new targets
for therapy.
Figure 1 - Model of the 3-dimensional structure of the
Gadd45 protein.
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2. Identification and characterisation
of novel genes involved in normal myelopoiesis and myeloid
leukaemia
We have previously utilised a powerful gene expression-profiling
(microarray) approach to identify genes associated with proliferation,
survival, promoting or blocking of differentiation in myeloid
progenitors.
From this we have:
Used detailed gene expression analysis, computational approaches
and comparison with other myeloid cell line models and leukaemia
profiling studies to further define and prioritise genes
of interest.
Begun functional testing of key candidate regulatory genes
in a myeloid cell line model and in primary haemopoietic progenitors
in vitro.
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3. Australian Familial Haematological
Cancer Study
Together with the Familial Cancer unit we are developing
a resource for biomedical research into the genetic basis
of familial haematological malignancy. We will use established
high throughput methods of mutation analysis as well as targeting
multiple "candidate genes" to identify mutations
which contribute to familial haematological malignancies.
Such genes are predicted to be important regulators of blood
cell growth and differentiation and are likely to also play
a role in sporadic haematological malignancies. To date we
have:
Identified a number of kindreds with familial haematological
malignancy, recorded pedigree data, collected clinical and
demographic data about family members, and stored biological
samples (blood, tissue) from both affected and unaffected
family members.
Begun genetic analysis of one large family of interest.
Identification of genes contributing
to myeloid leukaemia. The images above show an overhead view
of plastic wells containing cells growing in artificial media.
Genes derived from a leukaemia sample were introduced into
normal target cells which were aliquoted into the right-hand
panel of wells. Growth genes from this leukaemia sample can
be identified by their ability to allow these cells to grow,
which turns the media yellow. Cells without growth genes do
not survive and hence the media remains pink. For comparison,
cells which do not contain any leukaemia genes were aliquoted
into the left-hand panel of wells.
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