The Molecular Function And Role Of The New Metastasis Suppressor NDRG1 In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$226,425.00
Summary
With cancer now a leading cause of death in Australia, finding new ways to treat this disease is crucial. Iron is critical for cancer cell growth and metastasis, thus agents that bind iron (called iron chelators) can be used to treat cancer. These drugs up-regulate the gene NDRG1, which has been shown to prevent tumour spread. The role of NDRG1 in tumour growth and spread of cancer cells will be examined as this may lead to novel therapies against cancer (e.g. the use of novel iron chelators).
Convergence Of Activated C-myb And Wnt Pathways In Colon Cancer
Funder
National Health and Medical Research Council
Funding Amount
$256,320.00
Summary
c-myb is essential for the normal biology of the blood system and the colon. It is involved in regulating the balance between the production of new cells and their timely removal once they have completed their assigned tasks. Another group of factors that make up theWnt pathway also contribute to the normal biology of the colon in man and mouse. Defects that lead to too much c-myb and ineffective control of the Wnt pathway appear to work together to increase the risk and severity of colon cancer ....c-myb is essential for the normal biology of the blood system and the colon. It is involved in regulating the balance between the production of new cells and their timely removal once they have completed their assigned tasks. Another group of factors that make up theWnt pathway also contribute to the normal biology of the colon in man and mouse. Defects that lead to too much c-myb and ineffective control of the Wnt pathway appear to work together to increase the risk and severity of colon cancer. This project is designed to specifically test this observation in animals. In addition it examines in fine detail how c-myb levels increase in colon cancer and how it combines with the Wnt pathway to regulate other genes in colon cancer.Read moreRead less
Identification And Functional Evaluation Of MicroRNAs And Their Target Genes That Regulate Breast Cancer Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$607,773.00
Summary
Breast cancer is the major cause of cancer-associated death in Australian women. Once the disease has spread to other organs, as occurs in about 20% of cases, our ability to treat the disease is limited and mortality is high, leading to an enormous social and economic cost New therapies for advanced disease are needed urgently. To facilitate this, we need to understand the molecular regulation of metastasis to distant organs and use this knowledge to develop new molecular targeted therapies.
The Role Of CD30 Overexpression In CD30-positive Non-Hodgkins Lymphomas
Funder
National Health and Medical Research Council
Funding Amount
$457,242.00
Summary
The CD30 molecule sits on the surface of normal blood cells, but in a type of cancer called Lymphoma, CD30 concentration is high. The level of expression of CD30 may determine if the cancer cell is killed by the normal defense mechanisms or is able to grow uncontrollably. We are studying the control elements of the CD30 gene to understand how control is lost when the cell becomes cancerous. This knowledge may lead to therapeutic strategies to control lymphoma.
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
CHARACTERIZATION OF THE NOVEL LEUKEMIA-INDUCING GENE MLF1
Funder
National Health and Medical Research Council
Funding Amount
$393,750.00
Summary
All of the circulating blood cells (including red cells and white cells) arise from haemopoietic stem cells found in the adult bone marrow. Stem cells gradually develop into one cell type. Once they have started down a particular pathway, they no longer generate cells of another pathway (e.g. once a stem cell begins to develop into red blood cells, they do not change into white cells). However, there are a few examples of mature cells that have changed pathways. We generated a red blood cell lin ....All of the circulating blood cells (including red cells and white cells) arise from haemopoietic stem cells found in the adult bone marrow. Stem cells gradually develop into one cell type. Once they have started down a particular pathway, they no longer generate cells of another pathway (e.g. once a stem cell begins to develop into red blood cells, they do not change into white cells). However, there are a few examples of mature cells that have changed pathways. We generated a red blood cell line, which has on occasions changed into macrophages (white blood cells) when grown under stressful conditions. Using these cells, we identified a gene, HLS7, which was involved in the change to macrophages. An American group has independently shown this gene can cause leukemia (blood cancer). We have shown HLS7 has dramatic effects on normal blood development and, together with its effect on leukemias, demonstrates its importance to the blood system. Through our studies on how HLS7 works, we have identified another gene, Madm, which may be an important regulator of HLS7. We plan to investigate the normal function of HLS7, how it interacts with Madm and how it causes leukemias. Analysis of these genes will further our knowledge in this field of blood cell development and cancer formation.Read moreRead less
Isolation And Characterisation Of Mouse Mammary Stem And Progenitor Cells
Funder
National Health and Medical Research Council
Funding Amount
$540,202.00
Summary
We have discovered the rare adult stem cell from which all breast epithelial tissue is formed. A single stem cell was found to be capable of giving rise to various cell types in the breast, including the secretory units that produce milk and the ductal cells that transmit milk to the nipple. These cell types are responsible for the majority of human breast tumours. However, the precise 'cell of origin' from which cancers ultimately develop is not known. We recently also found that the stem cell ....We have discovered the rare adult stem cell from which all breast epithelial tissue is formed. A single stem cell was found to be capable of giving rise to various cell types in the breast, including the secretory units that produce milk and the ductal cells that transmit milk to the nipple. These cell types are responsible for the majority of human breast tumours. However, the precise 'cell of origin' from which cancers ultimately develop is not known. We recently also found that the stem cell population is expanded in at least one model of mammary tumours, suggesting that some tumours may arise from the breast stem cell itself. Using mouse models and cellular assays, our aim is to characterise, for the first time, the hierarchy of stem, progenitor ('daughter cells') and mature cells in the mammary gland. These studies will provide insight into the various cell types that give rise to different types of breast cancer. An important evolving concept in cancer biology is that a rare population of cells resident within a tumour, termed 'cancer stem cells', have indefinite growth potential and drive tumour growth. These cells could even account for resistance to conventional anti-cancer treatment, as cells with stem cell-like properties would be able to proliferate extensively and form new tumours. We will apply our knowledge of normal mammary stem cells to determine whether cancer stem cells are indeed present in mouse tumours. Those findings will have direct relevance to human breast cancer. Utlimately, we wish to identify specific cell surface proteins on stem and precursor cells that could provide therapeutic targets. Our studies will provide new insights into the cell types from which breast cancer arise, and how their fate and tumour-forming capacity can be modified by altering gene expression. Delineation of cancer-prone cells and cancer stem cells could reveal new markers and provide new therapeutic strategies to target breast cancer.Read moreRead less
Interplay Between Mutant P53 And PML; Implications For Tumourigenesis.
Funder
National Health and Medical Research Council
Funding Amount
$483,737.00
Summary
The most important agent of the body for fighting cancer is the cellular protein p53. In more than 50% of all human cancers, it looses its anticancer properties through mutation. In an insidious manner this new mutant form then acts to promote cancer. To better treat cancer we need to understand how mutant p53 functions. We will study how it interacts with its molecular partners in cancer cells.