Control of tumour growth by oncogene-induced senescence
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Discovering how senescence controls tumour initiation, growth and progression.
Cellular senescence' is the irreversible loss of a cell's ability to divide and is an important mechanism of tumour suppression that is activated in benign lesions yet circumvented in the malignant tumour. It is induced by a variety of intracellular stresses including activated oncogenes, DNA damage, oxidative stress and telomere dysfunction. As was noted in Cell recently, "Although recent work has begun to identify the molecules that enforce senescence in response to different signals, we still have only a rudimentary understanding of the components that comprise and execute the senescence program."
During studies of the vasculature by the Vascular Biology group at The Centenary Institute, SENEX was identified as a potent inducer of senescence and we believe this gene is a major player in the oncogenic senescence pathway. We are studying how SENEX regulates senescence of the tumour cells as well as the tumour vasculature. Of particular interest is what signalling pathways SENEX uses to tell the cell to senesce, and what factors - found within the cell or the tumour - control SENEX expression. This is a relatively new area, both for the Centenary Institute and the cancer research community in general, and is progressing at an exciting pace.
Potential research areas for PhDs topics
Senescence is a very active area presently, and the opportunities are evolving very rapidly. Some potential projects are listed below.
- Regulation of senescence by inflammatory cells and cytokines.
- The effects of senescence on tumour angiogenesis.
- The role of the DNA damage response in oncogene-induced senescence.
- Tumour hypoxia and senescence.
- Breast tumour and senescence - an unexpected role in metastasis?
- SENEX and senescence in breast cancer
We have many projects that would suit an Honours student.
These projects use molecular biology and cell biology to investigate senescence. Techniques include: real-time and in vivo imaging, confocal microscopy, RNAi, qrtPCR, immunohistochemistry, flow cytometry, tissue culture, invasion assays, angiogenesis assays, and apoptosis ELISAs. We have access to a large cohort of patient samples so that we can investigate senescence in patients. We also are generating transgenic models that will prove invaluable in the future.
Most students in the laboratory are supported by an Australian Post-graduate Award or other scholarship. Please contact me directly for further details.
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The opportunity ID for this research opportunity is: 832