Yale Genetics

Our Department Faculty/Labs Graduate Program Medical Genetics Directory

    Forget, Bernard

    Professor of Medicine and Genetics

    * B.A. University of Montreal, Canada, 1959
    * M.D. McGill University, Montreal, Canada, 1963

    Research Interests:   

    * Molecular Genetics of Erythroid Cell Differentiation
    * Hematopoietic Stem Cell Biology

    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.

    Current Research:   

       
    My laboratory is involved in a research program concerned with the mechanisms of normal and abnormal gene expression in hematopoietic cells with an emphasis on genes that are expressed during red blood cell differentiation. A major research effort is also devoted to the study of the transcriptional regulation of genes encoding red cell membrane skeleton proteins such as spectrin and ankyrin. Spectrin and ankyrin genes are part of multigene families, members of which are differentially expressed in different tissues. In addition, a number of genetic diseases of the red cell (hereditary hemolytic anemias) are due to disorders of spectrin and ankyrin, the molecular basis of which is under investigation. The laboratory is also studying differential gene expression in highly enriched primitive hematopoietic stem cells, as well as the overall gene expression profile of various types of differentiated hematopoietic cells in order to elucidate transcriptional regulatory circuits during hematopoiesis. 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 as well as other acquired diseases, and research directed at the purification of reconstituting hematopoietic stem cells for the purposes of gene therapy.

    Representative Publications

    Lambert J-F, Liu M, Colvin GA, Dooner M, McAuliffe CI, Becker PS, Forget, BG, Weissman, SM, Quesenberry, PJ. Marrow stem cells shift gene expression and engraftment phenotype with cell cycle transit. J. Exp. Med., 197:1563-1572, 2003.

    Gallagher, P.G., Zhang, Z., Feig, S.A., Morrow, J.M., Forget, B.G. Mutation of a highly conserved isoleucine disrupts hydrophobic interactions in the ab spectrin self-association binding site. Lab. Invest. 84:229-234, 2004.

    Wong, E.Y., Lin, J., Forget, B.G., Bodine, D.M., Gallagher, P.G. Sequences downstream of the erythroid promoter are required for high-level expression of the human a-spectrin gene. J. Biol. Chem. 279:55,025-55,033, 2004.

    Wang, L, Arcasoy, M.O., Watowich, S.S., Forget, B.G. Cytokine signals through STAT3 promote expression of granulocyte secondary granule proteins in 32D cells. Exp. Hematol. 33:308-317, 2005.

    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 (in press) 2005

    Costa, D, Lozovatsky, L., Gallagher, P., Forget, B.G. A novel splicing mutation of the a-spectrin gene in the original hereditary pyropoikilocytosis kindred. Blood (in press) 2005.

    Contact Information:

    bernard.forget@yale.edu
    Our Department Faculty/Labs Graduate Program Medical Genetics Directory