Identification Of Novel Targeted Therapies For JAK2-driven Leukemogenesis
Funder
National Health and Medical Research Council
Funding Amount
$392,717.00
Summary
Many leukemias are caused by particular signalling molecules becoming too active in blood cells. My research focusses on the molecules that are required by leukemic cells for their growth and survival. I will use mice that are prone to developing leukemia to study how these leukemias can be treated with drugs that block specific molecules. My goal is to discover new ways to treat leukemias that work better and have fewer side effects than current treatments.
In Vivo Modelling Of WIF1 In Bone Development And Tumourigenesis
Funder
National Health and Medical Research Council
Funding Amount
$402,796.00
Summary
Osteosarcoma is the most common primary cancer of the bone. We identified Wnt inhibitory factor 1 (WIF1), a secreted protein that inhibits the Wnt cell growth pathway, to be silenced in osteosarcoma. We propose to investigate the role of WIF1 in normal development, how its loss contributes to cancer progression, and whether treatment with WIF1 protein can inhibit tumour growth. Our overall aim is to discover key molecules, which can be targeted therapeutically to inhibit osteosarcoma growth..
The future of cancer therapy lies in the tailoring of treatment to the characteristic of individual tumour. We have previously identified a subset of breast tumours that are characterised by the presence of large excess of proteins called D-type cyclins. Similar overexpression of cyclin D1 has been shown to lead to the development of cancer in mammary gland in animal models. In normal cells, D-type cyclins are degraded rapidly, therefore the regulation of protein degradation, or proteolysis, is ....The future of cancer therapy lies in the tailoring of treatment to the characteristic of individual tumour. We have previously identified a subset of breast tumours that are characterised by the presence of large excess of proteins called D-type cyclins. Similar overexpression of cyclin D1 has been shown to lead to the development of cancer in mammary gland in animal models. In normal cells, D-type cyclins are degraded rapidly, therefore the regulation of protein degradation, or proteolysis, is crucial in preventing the accumulation of D-type cyclins. In the subset of breast cancers we have identified, D-type cyclin proteolysis is defective. We, and others, have obtained evidence for the involvement of the SKP2 gene in the proteolysis of D-type cyclins. SKP2 has also been shown to be required for the proteolysis of another important protein, called p27. In the clinic, accumulation of p27 in tumours is used as a good prognostic indicator. However, some exceptions have been found where the accumulation of p27 correlates with aggressive tumours. As D-type cyclins are able to counteract the effect of p27, we hypothesise that the aggressive behaviour of these tumours is due to the simultaneous accumulation of D-type cyclins and that this is due to a mutation in the SKP2 gene. The experiments described in this proposal are designed to test this hypothesis. As the choice of treatment is affected by the interpretation of p27 levels, the results obtained from this study may have a direct impact in the clinic.Read moreRead less
Analysis Of Apoptotic Pathways To Develop Better Therapies For Unresponsive Cancers.
Funder
National Health and Medical Research Council
Funding Amount
$130,807.00
Summary
Tight control of the balance between cellular survival and death is important for normal development and to avoid numerous diseases. Inappropriate survival of precancerous cells can contribute to oncogenesis. Anti-cancer therapies act by inducing a cellular self-destruct program in tumour cells, and blocks in pathways controlling this process can lead to resistance to anti-cancer treatments. Defining cell death pathways will enable the development of better therapies for incurable cancers.
This project seeks to evaluate the role of new cell growth regulating pathway in the development of moles and melanoma. In particular, we will determine at which stage during tumour progression disruption of this pathway occurs, and whether its loss is associated with melanoma patient survival. Identification of the cancer-related changes that occur when this pathway is aberrant may ultimately lead to the development of novel therapies to treat melanoma.
Acute myeloid leukaemia (AML) is a major health problem with only about one third of patients being cured. In addition therapies have changed little over the last 20 years. However there is optimism that with greater knowledge of the biochemical changes in AML that are caused by genetic mutations, more effective treatments will be developed. This project therefore aims to increase understanding of the biochemical interplay between two proteins called c-Cbl and Flt3 that are altered in AML.
The Role Of MC1R Polymorphism In Skin Cancer Risk Phenotypes
Funder
National Health and Medical Research Council
Funding Amount
$480,750.00
Summary
Sunsmart campaigns are a unifying element in the lives of many Australians who wish to ensure protection against the damaging effects of ultraviolet rays in sunlight. Indeed, Australians have the highest incidence of UV-induced melanoma in the world. Although it is evident that lighter skin colours are more susceptible to sun damage, the relationship between sun exposure, skin type and melanoma formation is less clear. An essential first step in understanding the complex interactions that give r ....Sunsmart campaigns are a unifying element in the lives of many Australians who wish to ensure protection against the damaging effects of ultraviolet rays in sunlight. Indeed, Australians have the highest incidence of UV-induced melanoma in the world. Although it is evident that lighter skin colours are more susceptible to sun damage, the relationship between sun exposure, skin type and melanoma formation is less clear. An essential first step in understanding the complex interactions that give rise to melanoma, and in identifying individuals that have a high susceptibility, is to reduce phenotypic analyses to genotypic classifications. As pigmentation phenotype is a factor of central importance in determining an individuals risk for melanoma, characterisation of the genes underlying the physical qualities of human eye, hair and skin colour will give a more direct and accurate genotypic assessment of risk. Results from an epidemiology study of melanoma patients in Queensland have identified a number of genetic changes within the melanocyte stimulating hormone receptor (MC1R) gene that associate with skin, hair and eye colour as well as with incidence of melanoma. Further investigation of MC1R gene alleles which segregate with skin and hair colours will provide the beginning for a whole new genotype-based classification of skin colour and melanoma risk, and will significantly contribute to our understanding of what makes some individuals highly susceptible to melanoma while others are not. Indeed, MC1R polymorphisms may numerically be the most important melanoma predisposition gene yet identified, exerting its effects as one of those common genes of small effect which may account for much more of the case load in melanoma than rarer genes of large effect. Studies such as this will enable powerful genotyping methods to be employed in identification of those individuals at highest risk for melanoma and other skin cancers.Read moreRead less
CHARACTERISATION OF A NOVEL REGULATOR OF PHOSPHOINOSITIDE 3-KINASE-MEDIATED CELL PROLIFERATION AND PLATELET SIGNALLING
Funder
National Health and Medical Research Council
Funding Amount
$500,091.00
Summary
Critical functions such as cell growth, cell death and metabolism, are tightly controlled by key proteins which respond to specific stimuli. Perturbation of this process may lead to uncontrolled growth and cancer. This project proposes to examine the potential of a novel protein (an enzyme) as a physiological regulator of cell growth. It is proposed that this enzyme may function as a brake in preventing the evolution of a cancerous state. We will also study the ability of the novel enzyme to inf ....Critical functions such as cell growth, cell death and metabolism, are tightly controlled by key proteins which respond to specific stimuli. Perturbation of this process may lead to uncontrolled growth and cancer. This project proposes to examine the potential of a novel protein (an enzyme) as a physiological regulator of cell growth. It is proposed that this enzyme may function as a brake in preventing the evolution of a cancerous state. We will also study the ability of the novel enzyme to influence other diverse functions, such as uptake of glucose, and blood clot initiation.Read moreRead less
I am a cellular biologist studying lineage commitment and differentiation in the mammary gland. Key interests include defining transcriptional regulators that are important for mammary gland development and oncogenesis, and the characterisation of normal