Identification And Characterization Of Substrates Of Tyrosine Kinases Involved In Hematopoiesis And Leukemia
Funder
National Health and Medical Research Council
Funding Amount
$241,527.00
Summary
The development and maintenance of tissues in mammals are tightly controlled and complex processes involving the growth, maturation and survival of vast numbers of cells of various types. In cancer, the cell's capacity to faithfully regulate these processes is diminished or lost. Many of the proteins that are essential for growth control are produced by an important class of genes called proto-oncogenes; literally, the prototypes of cancer-causing genes. Naturally occurring mutations in these ge ....The development and maintenance of tissues in mammals are tightly controlled and complex processes involving the growth, maturation and survival of vast numbers of cells of various types. In cancer, the cell's capacity to faithfully regulate these processes is diminished or lost. Many of the proteins that are essential for growth control are produced by an important class of genes called proto-oncogenes; literally, the prototypes of cancer-causing genes. Naturally occurring mutations in these genes have been identified in man and are likely to play a major role in the initiation and progression of distinct human malignancies. A significant number of proto-oncogenes are enzymes called protein tyrosine kinases (PTKs). Research has shown that the function of PTKs is to relay growth signals or other regulatory signals from the outer surface of the cell to specific target proteins inside the cell. These target proteins are needed to relay the signal to other target molecules and so on. This highly ordered process, involving a specific sequence of proteins, ensures that cells respond appropriately to a given signal. Our research focuses on identifying and studying the immediate targets of PTKs with the broad aim of understanding how PTKs control growth in normal and cancerous cells. We have recently developed a method that has enabled us to identify a new protein that may regulate the growth of blood cells. The research proposed here aims to extend our preliminary observations showing that the growth of specific types of blood cells is inhibited by this protein. We also plan to search for new targets of a PTK that is involved in leukemia. The findings of this research will provide important insight into how blood cells are regulated in health and disease.Read moreRead less
Use Of Retroviral Expression Libraries To Characterise Mechanisms Of Drug Resistance In Leukaemia.
Funder
National Health and Medical Research Council
Funding Amount
$362,545.00
Summary
At present, treatment of leukaemia is based either on established chemotherapeutic drug treatment or newly identified inhibitor drugs currently being tested as part of clinical trials. Both these treatments are known to induce or select for resistance to the drugs in some cases. Resistance usually reduces the success rate of any further treatment with the same or similar drugs. To discover possible ways of overcoming drug resistance it is important to understand the mechanisms that are responsib ....At present, treatment of leukaemia is based either on established chemotherapeutic drug treatment or newly identified inhibitor drugs currently being tested as part of clinical trials. Both these treatments are known to induce or select for resistance to the drugs in some cases. Resistance usually reduces the success rate of any further treatment with the same or similar drugs. To discover possible ways of overcoming drug resistance it is important to understand the mechanisms that are responsible. To date a number of mechanisms that cause resistance are known, but there are still unidentified mechanisms that are associated with drug resistance. The aim of our work is to use a new method to identify unknown drug resistance mechanisms in leukaemia. Once a mechanism is identified, we will determine its relevance in leukaemia by screening a number of patients that have shown resistance to treatment. If identified as a common mechanism of resistance in leukaemic patients, we will test possible agents able to prevent drug resistance that could be used in conjunction with drug during treatment, and to screen new drugs for susceptibility to resistance mechanisms. Diagnostic tests to detect the presence of the known resistance mechanisms prior to treatment could be used in selection of the most appropriate drug combinations for individual patients. Some of the known drug resistance mechanisms that occur in leukaemia are also operative in other forms of cancer and the project is of general relevance to cancer chemotherapy.Read moreRead less