Analysis Of The Role Of Polycomb Genes In Normal And Diseased Breast Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$362,810.00
Summary
In Australia, 1 in 8 women will be diagnosed with breast cancer. Many will receive chemotherapy that will apparently eliminate the cancer. However, in approximately 1 in 3 of these women, cancer will recur. This is thought to be due to the presence of chemotherapy-resistant breast cancer stem cells. This project will study the parallels between the role of Polycomb genes in normal mammary stem cell maintenance and their role in breast cancer, in order to improve treatment and cure rates.
Deciphering Breast Cancer Heterogeneity To Improve Breast Cancer Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$851,980.00
Summary
Breast cancer is a very heterogeneous disease. Patients are often treated in a ‘one size fits all’ approach, but response to therapy remains quite disparate. To better personalise therapy, there is a pressing need to define the precise cell types and initiating genetic events that give rise to breast cancer. This application is focussed on understanding the molecular and cellular origins of breast cancer, with the potential of identifying new prognostic markers and therapeutic targets.
Hematopoietic Transplants From Autologous Pluripotent Cell Sources
Funder
National Health and Medical Research Council
Summary
This proposal investigates the utility of two types of patient-derived stem cells for transplantation into blood. These are induced pluripotent stem cells that are reprogrammed from specialized tissues such as skin cells, and stem cells derived using the genetic material of oocytes or sperm only ( one-parent embryos). Using the mouse, we are looking at the ability of these cells to form normal blood lineages after transplantation, and to repair blood in a mouse model for beta-thalassemia.
The Role Of Ap2a2 In Self-renewal Of Haematopoietic And Leukemic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$579,171.00
Summary
The daily replenishment of the blood system is dependent on the blood stem cell. A unique property of these stem cells is self-renewal where the stem cell function is preserved, whilst other daughter cells continue to divide. Our research investigates the molecular mechanisms that regulate stem cell self-renewal. This work has potential clinical application on at least two levels: expansion of stem cells for transplantation, and for attacking abnormal cancer cell self-renewal pathways.
Prof Lindeman's laboratory, co-headed with Dr Visvader, has played an influential role in the identification of mammary stem and progenitor cells, elucidation of the mammary epithelial cell hierarchy and gaining insights into how female hormones regulate mammary gland development and cancer. In parallel, I have established translational research platforms such as patient-derived tumour xenograft (PDX) models, which offer powerful preclinical models to test new drugs.
Haematopoietic Stem Cells From Human Pluripotent Stem Cells: The Future Of Bone Marrow Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$763,845.00
Summary
Blood stem cell transplantation is a vital therapy for patients with leukaemia following chemotherapy or for patients with bone marrow failure. Because many patients lack a donor, there is a need for an alternate source of stem cells. My laboratory will make blood stem cells from human pluripotent stem cells that will treat patients needing a transplant and will be a useful research tool to help us to understand what goes wrong in the blood system in a range of illnesses.
Patient Tailored Immunity Transplant For The Prevention Of Viral Infections Post Haemopoietic Stem Cell Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$567,967.00
Summary
Blood or bone marrow transplantation can cure leukaemia and related blood disorders, but patients are susceptible to infections in the period early after transplant. Infectious complications remain a leading cause of death among allogeneic transplant recipients. Our research aims to prevent the onset of infection using novel cell therapies to rapidly restore the immune system thus preventing the problems associated with the transplant process.
Using Direct Reprogramming To Generate And Rejuvenate Haematopoietic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,026,313.00
Summary
One of the greatest promises of regenerative medicine lies in our ability to reprogram any cell type of the body into any other cell type. Transdifferentiation is the conversion of one adult cell type to another and it is believed to be the next frontier in regenerative medicine therapies since it can be used in vivo for the direct conversion of one cell type into another. The outcomes of this grant will push the limits of these technologies to generate new regenerative medicine strategies.
Dementias affect a large number of Australians each year with the number of patients expected to triple by 2050. As such, there is need to develop a better model of this debilitating disorder to provide improved treatments. Mesenchymal stem cells, are relatively easy to obtain and grow, and are able to produce the key cell types in the brain. We can use these cells to identify the processes that control the production of brain cells, which will likely provide better treatment of this disease.