Understanding The Role Of RAS Mutations In Thyroid Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$463,854.00
Summary
My fellowship will examine the association of RAS mutations in thyroid cancer. RAS proteins are the most mutated in cancer and I will investigate how they work in thyroid cancer. RAS mutated thyroid cancer is more likely to cause death. This grant will be based in the pioneering lab of Prof Fagin at Memorial Sloan Kettering Cancer Center and the Garvan Institute of Medical Research. It is hoped by understanding these mutations, new treatments for thyroid cancer can be developed.
Is Mitochondiral STAT3 Necessary For K-Ras Induced Myeloid Leukaemias?
Funder
National Health and Medical Research Council
Funding Amount
$425,326.00
Summary
Myeloid leukaemia (ML) is a family of diseases characterized by the expansion of white blood cells, leading to death from haematopoietic complications. One common mutation that gives a proliferative advantage in ML is in the Ras oncogenes. We recently showed that signal transducer and activator of transcription 3 (STAT3) is necessary for the transforming potential of Ras due to its ability to support the metabolic changes necessary for tumour growth. This research will characterize the STAT3-dep ....Myeloid leukaemia (ML) is a family of diseases characterized by the expansion of white blood cells, leading to death from haematopoietic complications. One common mutation that gives a proliferative advantage in ML is in the Ras oncogenes. We recently showed that signal transducer and activator of transcription 3 (STAT3) is necessary for the transforming potential of Ras due to its ability to support the metabolic changes necessary for tumour growth. This research will characterize the STAT3-dependent metabolic changes in ML.Read moreRead less
Identification Of Novel Tumour Suppressors In Ras-mediated Tumourigenesis
Funder
National Health and Medical Research Council
Funding Amount
$580,504.00
Summary
Cancer is a cooperative process, involving mutations in several genes. Activation of the signaling protein, Ras, contributes to ~30% of human cancers, but alone is not sufficient for tumour formation. The identification of cooperating Tumour Suppressors (TSs), and their analysis in the vinegar fly, Drosophila, mammalian cells and mouse models is key to understanding cancer progression and for the development of therapeutic regimes
Molecular Regulation Of Tumourigenesis By The Polarity Determinant Scribble And Associated Proteins
Funder
National Health and Medical Research Council
Funding Amount
$614,421.00
Summary
Cell polarity is the property of cells to be spatially oriented in a tissue or organ. We have shown that Scribble, a key regulator of cell orientation, may keep tumour development in check. In this proposal, we will examine how disruption of Scribble promotes breast cancer using a combination of tissue culture studies and a newly established mouse model. Understanding how this new pathway can regulate breast tumour development may provide novel targets for therapeutic intervention in cancer.
Tumour cells are often characterized by defects in signaling pathways. One of the most important signaling cascades involved in the development of cancer is the EGFR-Ras-MAPK pathway. EGFR is often overexpressed in breast cancer, leading to enhanced Ras signaling (hyperactive Ras) and cell transformation. The proposed project aims to identify the molecular mechanisms that can downregulate hyperactive Ras and will make a valuable contribution to our understanding of EGFR-Ras related cancers.
Cancer is constantly being suppressed in our bodies by a process that stops damaged cells from growing: 'senescence'. The mechanism that translates the damage stimuli into this state of permanent cell arrest is only partially known. We have identified a protein that appears to drive this restraint. The possibility of manipulating this process to prevent and cure cancer makes it in important target to study.
Cell polarity is the property of cells to be spatially oriented in a tissue or organ. We have now shown that the gene Scribble, a key regulator of cell orientation, may keep tumour development in check. In this proposal, we will examine how disruption of Scribble promotes cancer using a combination of tissue culture studies and a newly established mouse model. Understanding how this new pathway can regulate tumour development may provide novel targets for therapeutic intervention in cancer.
The Role Of Plasma Membrane Microdomains In Cellualar Function
Funder
National Health and Medical Research Council
Funding Amount
$4,083,868.00
Summary
The planned research program relates to novel hypotheses regarding the role of cell surface domains in organising signalling pathways at the cell surface. The proposal will involve identifying the domains and molecules involved in specific signalling pathways and dissecting the formation and function of surface structures called caveolae. The findings will have huge importance for therapeutic strategies aimed at combating the cellular changes associated with cell transformation in cancer and oth ....The planned research program relates to novel hypotheses regarding the role of cell surface domains in organising signalling pathways at the cell surface. The proposal will involve identifying the domains and molecules involved in specific signalling pathways and dissecting the formation and function of surface structures called caveolae. The findings will have huge importance for therapeutic strategies aimed at combating the cellular changes associated with cell transformation in cancer and other human diseases.Read moreRead less