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Regulation Of Red Blood Cell And Platelet Formation By BHLH Proteins
Funder
National Health and Medical Research Council
Funding Amount
$422,600.00
Summary
Continuous production of normal blood cells by the bone marrow is a process critical to human life. Disruption of this process leads to diseases such as leukemia, aplastic anemia and myelodysplasia which have devastating consequences for affected patients. Pivotal to understanding these diseases is a knowledge of the regulation of normal blood production. Our laboratory works on a gene known as SCL that is critical for blood formation. We have recently shown that loss of SCL in adult bone marrow ....Continuous production of normal blood cells by the bone marrow is a process critical to human life. Disruption of this process leads to diseases such as leukemia, aplastic anemia and myelodysplasia which have devastating consequences for affected patients. Pivotal to understanding these diseases is a knowledge of the regulation of normal blood production. Our laboratory works on a gene known as SCL that is critical for blood formation. We have recently shown that loss of SCL in adult bone marrow leads to abnormalities in two types of blood cells, the red blood cells and the platelets. This grant will extend this important observation to understand how the production of these cells is altered and what is its consequence. Our studies will help clarify the basis of blood cell formation and may impact on how we diagnose and treat a wide variety of blood disorders.Read moreRead less
We will investigate how the master control gene, Kruppel-like factor 1, orchestrates production of red blood cells. We will use genetic and cell biology approaches to determine exactly how this factor interprets the genome blueprint in a cell specific manner. We will also determine how mutations in KLF1 cause human diseases such as congenital dyserythropoietic anemia and hereditary persistence of fetal haemoglobin. This has implications for reactivation of HbF in adults with sickle cell disease.
KLFs are master control genes that regulate the expression of many target genes to determine cell fate and to convert one cell fate to another. Mutations in KLFs cause human diseases. This grant will focus on the founding member of the KLF family, KLF1. We will use genomics techniques and animal models to determine how KLF1 works in normal blood cell production and in disease
The BHLH Transcription Factor LYL1 In Normal And Leukemic Hematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$520,945.00
Summary
This project aims to understand how two closely related genes, called SCL and LYL1, work together to control the production of normal red blood cells and when abnormally expressed, cause cancer of the white blood cells. We will specifcially examine how LYL1 causes a specific type of leukemia in children and determine blocking the function of LYL1 will be a useful way to kill leukemia cells.