Genetics; Hematology; Hematopoietic Stem Cells; Stem Cells; Erythroid Cells
Stem Cell Center, Yale: Stem Cell Niche and Homing | Transcriptional Regulation of Stem and Progenitor Cells
Dr. Forget's laboratory is involved in a research program studying the regulation of gene expression in hematopoietic cells, with an emphasis on erythroid-specific gene expression. Work is devoted to: study of the transcriptional regulation of genes encoding red cell membrane skeleton proteins such as spectrin and ankyrin; study of the molecular basis of mutations of these genes that cause hereditary anemias; and study of differential gene expression in highly enriched primitive hematopoietic stem cells. The study of the regulation of tissue-specific gene expression and hematopoietic stem cell-specific gene expression is relevant to the elucidation of mechanisms responsible for abnormal gene expression in genetic and acquired disorders of blood cells, and to research directed at the purification and manipulation of reconstituting hematopoietic stem cells for the purposes of gene therapy.
Specialized Terms: Molecular Genetics of Erythroid Cell Differentiation; Hematopoietic Stem Cell Biology
Extensive Research Description
Hematopoiesis provides an excellent model system for the study of gene expression and the molecular basis of disease. In hematopoietic cells, a number of genes are expressed in a tissue-specific and developmentally regulated fashion. Furthermore, a number of inherited and acquired disorders of hematopoietic cells are due to mutations that result in abnormal expression of these specialized genes.
- The normal structure and regulation of human globin gene clusters. Forget, B.G. and Hardison, R.C., In: Disorders of Hemoglobin. 2nd Ed. Steinberg, M.H., Forget, B.G., Higgs, D.R., Weatherall, D.J. (eds). Cambridge Univ. Press, New York, pp. 46-61, 20
- Thalassemia Syndromes Giardina PJ, Forget BG. In: Hoffman R et al, eds. Hematology: Basic Principles and Practice. 5th ed. Philadelphia, PA: Churchill Livingstone; 2008:535–563.
- Tolpinrud, W., Maksimova, Y.D., Forget, B.G., Gallagher, P.G. Nonsense mutations of the alpha spectrin gene in hereditary pyropoikilocytosis. Haematologica. 93:1752-1754, 2008.
- Sangerman, J., Maksimova, Y., Edelman, E.J., Morrow, J.S., Forget, B.G., Gallagher, P.G. Ankyrin-linked hereditary spherocytosis in an African-American kindred. Am. J. Hematol. 83:789-794, 2008.
- Kieusseian, A, Chagraoui, J., Kerdudo C, Mangeot, P., Gage, P., Navarro, N., Izac, B., Uzan, G., Forget, B.G., Dubart-Kupperschmitt, A. Expression of Pitx2 in stromal cells is required for normal hematopoiesis. Blood 107:492-500, 2006.
- Zhang, H., Degar, B., Rogoulina, S., Resor, C., Booth, C., Sinning, J., Gage, P., Forget, B.G. Hematopoiesis following disruption of the Pitx2 homeodomain gene. Exp. Hemat. 34: 167-178, 2006
- Forget, B.G. De novo and acquired forms of alpha thalassemia. Curr. Hematol. Rep. 5;11-14, 2006.