Jabbour Group - Cytokines, AML
Transformations that cause leukaemia allow cells to escape controls on unrestricted cell proliferation, in part by an increased resistance to cell death. This not only contributes to the transformation process but also to resistance to treatment. Our aim is to understand how cell death and survival signals are regulated in normal blood progenitor cells and the molecular mechanisms and consequences of their deregulation in leukaemic cells.
2015 group L-R: Ms Karla Fischer, Ms Carmel Daunt, Dr Anissa Jabbour
Our Laboratory is interested in how cytokines signal cell survival and proliferation, and how these pathways are deregulated in Acute Myeloid Leukaemia. Our group aims to understand how key kinase pathways, activated by the cytokines Interleukin (IL)-3 and GM-CSF, maintain healthy proliferation of myeloid progenitor cells and how deregulation of these kinases affects growth of leukaemia cells.
Our goals are to:
- Determine the role of key IL-3/GM-CSF activated kinases, in particular JAK2, AKT and IkappaB kinase (IKK)
- Identify how JAK2, AKT and IKK regulate cell survival signals
- Determine how activation of IL-3/GM-CSF receptors leads to regulation of the transcription factor and tumour suppressor p53
- Use genetic and pharmacological approaches to establish the efficacy of inhibiting specific kinases to treat chemotherapy resistant leukaemia
Bloomer DT, Kitevska T, Brand IL, Jabbour AM, Nguyen H, Hawkins CJ. Modeling Metazoan Apoptotic Pathways in Yeast. Methods in Molecular Biology. 2016:1419, 161-183.
Bandopadhayay, P., Jabbour, A., Riffkin, C.D., Salmanidis, M., Gordon, L., Popovski, D., Rigby, L., Ashley, D.M., Watkins, D.N., Thomas, D.M., Algar, E.M., Ekert, P.G. The oncogenic properties of EWS/WT1 of desmoplastic small round cell tumors are unmasked by loss of p53 in murine embryonic fibroblasts, BMC Cancer, 2013:13, 1-14.
Brumatti, G., Salmanidis, M., Kok, C.H., Bilardi, R.A., Sandow, J.J., Silke, N., Mason, K.D., Visser, J.A.L., Jabbour, A., Glaser, S.P., Okamoto, T., Bouillet, P., D'Andrea, R.J., Ekert, P.G. HoxA9 regulated Bcl-2 expression mediates survival of myeloid progenitors and the severity of HoxA9-dependent leukemia, OncoTarget, 2013:4(11),1933-1947.
Salmanidis, M., Brumatti, G., Narayan, N., Green, B.D., van den Bergen, J.A., Sandow, J.J., Bert, A.G., Silke, N., Sladic, R., Puthalakath, H., Rohrbeck, L., Okamoto, T., Bouillet, P., Herold, M.J., Goodall, G.J., Jabbour, A., Ekert, P.G. Hoxb8 regulates expression of microRNAs to control cell death and differentiation. Cell Death and Differentiation, 2013:20(10), 1370-1380.
Thomas D., Powell J.A., et al. Targeting acute myeloid leukemia by dual inhibition of PI3K signaling and Cdk9-mediated Mcl-1 transcription. Blood, 2013:122(5), 738-748.
Green B.D.,* Jabbour A.M.,* et al. Akt1 is the principal Akt isoform regulating apoptosis in limiting cytokine concentrations. Cell Death Differ. 2013:20(10), 1341-1349. (*equal contribution).
Sandow JJ, Jabbour AM et al. Cytokine receptor signaling activates an IKK-dependent phosphorylation of PUMA to prevent cell death. Cell Death Differ. 2012:19, 633-641.
Jabbour, A., Gordon, L., Daunt, C.P., Green, B.D., Kok, C.H., D'Andrea, R.J., Ekert, P.G. p53-dependent transcriptional responses to interleukin-3 signaling, PLoS ONE, 2012:7(2), 1-11.