Genetic Fate Mapping Of Mesenchymal Stem Cell Origins And Investigating Their Contribution To Developmental Haematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$611,525.00
Summary
Mesenchymal stem cells are a population of cells that reside in various organs in the body and are thought to contribute to tissue repair. However little is known about the developmental origins and identity of these cells. I will investigate where these cells originate from, their molecular identity and how they relate to blood development. These findings will help in developing protocols to manipulate these cells to repair damaged organs. This study will also inform current attempts to generat ....Mesenchymal stem cells are a population of cells that reside in various organs in the body and are thought to contribute to tissue repair. However little is known about the developmental origins and identity of these cells. I will investigate where these cells originate from, their molecular identity and how they relate to blood development. These findings will help in developing protocols to manipulate these cells to repair damaged organs. This study will also inform current attempts to generate blood stem cells.Read moreRead less
Haematopoietic Stem Cell Glycome Regulates Outcome Of Niche Interactions
Funder
National Health and Medical Research Council
Funding Amount
$913,729.00
Summary
Hematopoietic stem cells (HSC) reside in the bone marrow (BM) and make all the cells of the blood system. We have found a factor in the BM which when blocked, puts normal HSC to sleep helping them survive chemotherapy. This means cancer patients should suffer less side-effects from their therapy. This factor also helps leukaemia stem cells (LSC) resist chemotherapy. Inhibitors may a) reduce patient mortality caused by chemotherapy and b) sensitise LSC to chemotherapy enabling long-term cure.
Inducible Caspase 9 Suicide Gene To Improve The Safety Of Donor T Cell Addback After Haploidentical Stem Cell Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$566,232.00
Summary
In bone marrow transplantation, donor immune cells are important for fighting cancer cells and infections but can also attack healthy tissues, causing graft-versus-host disease (GVHD). We will use gene technology to insert a safety switch called inducible capase 9 (iCasp9) into the donor immune cells which will make them susceptible to an otherwise non-toxic chemical. This will make it safer to boost the recipients’ immunity because these cells can be rapidly eliminated if GVHD occurs.
Investigating The Contribution Of Distinct Mitochondrial Cell Death Pathways To Platelet Survival And Function
Funder
National Health and Medical Research Council
Funding Amount
$635,247.00
Summary
Platelets are small blood cells that form clots to stop bleeding. We have found new and unexpected roles for 2 distinct pathways that regulate cell death in the process of blood clot formation. We will study the precise role of these pathways in blood clot formation, and determine whether they may also regulate the survival of platelets stored by the blood bank for transfusion. These studies will provide new insight into the role of cell death pathways in blood clot formation, and may help to im ....Platelets are small blood cells that form clots to stop bleeding. We have found new and unexpected roles for 2 distinct pathways that regulate cell death in the process of blood clot formation. We will study the precise role of these pathways in blood clot formation, and determine whether they may also regulate the survival of platelets stored by the blood bank for transfusion. These studies will provide new insight into the role of cell death pathways in blood clot formation, and may help to improve current protocols for storing plateletsRead moreRead less
Epigenetic Regulation Of Self Renewal And Lineage Commitment In Haematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$1,104,930.00
Summary
The process by which all our mature blood cells are produced and sustained remains largely unknown. Underpinning the cell fate decisions made through blood cell development is the tightly regulated expression of key genes and proteins that subsequently direct the process of blood cell differentiation. This project will aim study and uncover the molecular mechanisms that coordinate the key gene expression programs that lead to normal blood cell development.
Hemoglobin is the major protein in red blood cells and is essential for the transport of oxygen from the lungs to the tissues. The disorders of hemoglobin production are the commonest genetic diseases world-wide. These diseases can be markedly improved with elevation of the form of hemoglobin produced by the developing fetus, fetal hemoglobin. We have identified a key factor important for fetal gene expression. We will now determine whether manipulation of this factor can cure hemoglobin disorde ....Hemoglobin is the major protein in red blood cells and is essential for the transport of oxygen from the lungs to the tissues. The disorders of hemoglobin production are the commonest genetic diseases world-wide. These diseases can be markedly improved with elevation of the form of hemoglobin produced by the developing fetus, fetal hemoglobin. We have identified a key factor important for fetal gene expression. We will now determine whether manipulation of this factor can cure hemoglobin disorders.Read moreRead less
A Phase I Study Of PiggyBac CD19 Specific Chimeric Antigen Receptor T-cells For Therapy Of Persistent And Relapsed B-cell Leukaemia And Lymphoma Post Allogeneic Stem Cell Transplantation (The CARTELL Study).
Funder
National Health and Medical Research Council
Funding Amount
$357,590.00
Summary
Most people with relapsed leukaemia and lymphoma after bone marrow transplant die of their disease. Inserting special genes into immune cells can enable them to kill leukaemia and lymphoma and has led to dramatic cures, but there is little experience in bone marrow transplant patients. We will make leukaemia and lymphoma specific immune cells from normal bone marrow transplant donors, then administer the immune cells to transplant patients to assess their safety and effectiveness.
A Clinical Trial Of Partially HLA-matched Unrelated Donor Microtransplantation For Prevention Of Relapse In Patients With Acute Myeloid Leukaemia Ineligible For Standard Haemopoietic Stem Cell Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$154,828.00
Summary
Acute myeloid leukaemia has a poor prognosis in patients unable to undergo bone marrow transplant, in particular in the elderly. No proven therapy improves their poor outcome. There is an urgent need to identify clinically applicable, non-toxic therapies for this group of patients. We will perform a clinical trial of "microtransplantation" using unrelated stem cell donors in combination with chemotherapy to try to reduce the relapse rate in these patients without the toxic effects of standard st ....Acute myeloid leukaemia has a poor prognosis in patients unable to undergo bone marrow transplant, in particular in the elderly. No proven therapy improves their poor outcome. There is an urgent need to identify clinically applicable, non-toxic therapies for this group of patients. We will perform a clinical trial of "microtransplantation" using unrelated stem cell donors in combination with chemotherapy to try to reduce the relapse rate in these patients without the toxic effects of standard stem cell transplantation.Read moreRead less
Understanding Autophagy In Haematopoiesis And Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$500,813.00
Summary
Blood cancers such as leukaemia are among the most deadly types of cancer and new treatments are desperately needed to improve survival. We have identified a new pathway that is activated when cells undergo stress. This pathway controls the survival of normal blood cells and also appears to be very important in the way cancer cells respond to chemotherapy. We will characterize this pathway in normal blood cells and use this information to develop new treatments to target and eliminate the leukae ....Blood cancers such as leukaemia are among the most deadly types of cancer and new treatments are desperately needed to improve survival. We have identified a new pathway that is activated when cells undergo stress. This pathway controls the survival of normal blood cells and also appears to be very important in the way cancer cells respond to chemotherapy. We will characterize this pathway in normal blood cells and use this information to develop new treatments to target and eliminate the leukaemia cells.Read moreRead less
A Novel Genetic Element Controlling Adult Hemoglobin Production
Funder
National Health and Medical Research Council
Funding Amount
$493,907.00
Summary
Disorders of the blood protein hemoglobin are the commonest genetic diseases worldwide, and include thalassemia and sickle cell disease. In this proposal we study two novel mouse lines that exhibit thalassemia, but lack any of the known genetic mutations that cause this disease. These mice afford us the opportunity to make unique observations into how hemoglobin is produced, and thereby provide a platform for new therapeutic approaches in these devastating diseases of the blood.