Research Synopsis

Transcriptional Regulation of Stem and Progenitor Cells

Yale investigators studying transcriptional regulation of stem cell self-renewal and differentiation have made very important discoveries. For example, Dr. Bernard Forget’s laboratory has shown that HoxB4 promotes normal hematopoietic stem cell growth by activating transcription of genes that are key for inhibition of apoptosis and suppression of cytokine signaling, and inhibiting genes that are required for hematopoietic differentiation. Dr. Diane Krause’s laboratory has discovered that the RNA binding protein RBM15, which is part of a chromosomal translocation in Acute Megakaryoblastic Leukemia affects differentiation by binding to the notch downstream regulator RBP-Jk. Dr. Arch Perkin's has identified several downstream target genes of the leukemogenic transcription factor Evi 1, and is now applying this knowledge to determine how Evi 1 works to induce leukemia. Dr Patrick Gallagher is a rising star in the molecular biology of the red cell in both health and disease. He has demonstrated the mechanism by which erythroid development is inhibited in EKLF null mice. Dr. Frank Ruddle has made seminal discoveries in the mechanisms of regulation of hox genes, whose expression controls cell differentiation programs throughout development as well as in adult stem cells.