Cell Signaling and Gene Expression
Hematopoiesis is the biological process that describes the production of blood cell lineages from bone marrow stem cells. Cell fate decisions by stem cells are manipulated through extracellular signals, interpreted by the cell through receptor-mediated signal transduction and ultimately controlled by changes in gene expression. Leukemia is a disease that results when blood cell differentiation and proliferation programs do not respond to normal control mechanisms.
Figure 1. The Hematopoietic Tree. During blood cell development, stem cells differentiate into lymphoid and myeloid lineages. With the exception of red blood cells, these lineages differentiate into mature subsets of white blood cells which comprise the immune system.
My research focuses on cell signaling and the regulation of gene expression by transcription factors (TFs) in normal blood cell development and leukemia. Recently, I have identified several gene targets of a TF, HOXA9, in normal immune cells and leukemic cell lines. DNA microarray technology, which allows for simultaneous analysis of thousands of genes, was employed to identify these target genes.
Figure 2. A DNA microarray. Each 50 micron spot contains DNA representing a different gene which is printed on to a 1 x 3 inch glass slide. Microarrays can contain hundreds to thousands of genes for many different species (480 human genes shown above). For analysis, the microarray is hybridized simultaneously with two fluorescently labeled samples and can be used to measure differential mRNA expression, comparative genomic hybridization (CGH) or DNA mutations, such as single nucleotide polymorphisms (SNPs).
Future research plans involve the continued use of DNA microarray technology to study other cell signaling pathways and gene targets of TFs in normal and leukemic immune cells. Through these studies, we expect to gain further insight into the cellular programs that control hematopoiesis, as well as identify drug targets for early diagnostic and superior therapeutic treatments of leukemia.
Ferrell CM, Dorsam ST, Ohta H, Humphries RK, Derynck MK, Haqq C, Largman C, and Lawrence HJ. Activation of stem-cell specific genes by HOXA9 and HOXA10 homeodomain proteins in CD34+ human cord blood cells. Stem Cells. May, 23(5):644-55, 2005.
Dorsam ST, Ferrell C, Dorsam G, Derynck M, Pau B, Bernstein H, Khodabakhsh D, Vijapurkar U, Haqq C, Largman C, and Lawrence HJ. The transcriptome of the leukemogenic homeoprotein HOXA9 in human hematopoietic cells. Blood. Mar 1, 103(5):1676-1684, 2004.