Abstract

Decreased expression of fetal hemoglobin around the time of birth represents the defining mechanism in the clinical manifestation of sickle-cell and beta-thalassemia syndromes. Therefore, prevention or reversal of that process represents a major clinical goal for the treatment of those diseases. An ongoing interest of the laboratory involves the study of fetal hemoglobin expression and regulation as hematopoietic stem cells undergo differentiation to become erythroid progenitor and precursor cells. Several approaches are used to manipulate the expression of fetal hemoglobin including signal transduction, chemical induction, and genetic modulation of the fetal globin gene. A current focus arose from clinical transcriptome studies that identified the potential involvement of let-7 microRNA in the regulation of fetal hemoglobin. Studies are now underway to explore let-7 microRNA related biology with a goal of developing novel therapies for hemoglobin disorders.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIADK025101-07
Application #
9148744
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2015
Total Cost
Indirect Cost

  Institution

Name
U.S. National Inst Diabetes/Digst/Kidney
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

de Vasconcellos, Jaira F; Tumburu, Laxminath; Byrnes, Colleen et al. (2017) IGF2BP1 overexpression causes fetal-like hemoglobin expression patterns in cultured human adult erythroblasts. Proc Natl Acad Sci U S A 114:E5664-E5672
de Vasconcellos, Jaira F; Byrnes, Colleen; Lee, Y Terry et al. (2017) Tough decoy targeting of predominant let-7 miRNA species in adult human hematopoietic cells. J Transl Med 15:169
de Vasconcellos, Jaira F; Lee, Y Terry; Byrnes, Colleen et al. (2016) HMGA2 Moderately Increases Fetal Hemoglobin Expression in Human Adult Erythroblasts. PLoS One 11:e0166928
Rabel, Antoinette; Leitman, Susan F; Miller, Jeffery L (2016) Ask about ice, then consider iron. J Am Assoc Nurse Pract 28:116-20
Krivega, Ivan; Byrnes, Colleen; de Vasconcellos, Jaira F et al. (2015) Inhibition of G9a methyltransferase stimulates fetal hemoglobin production by facilitating LCR/?-globin looping. Blood 126:665-72
Lee, Y Terry; de Vasconcellos, Jaira F; Byrnes, Colleen et al. (2015) Erythroid-Specific Expression of LIN28A Is Sufficient for Robust Gamma-Globin Gene and Protein Expression in Adult Erythroblasts. PLoS One 10:e0144977
de Vasconcellos, Jaira F; Fasano, Ross M; Lee, Y Terry et al. (2014) LIN28A expression reduces sickling of cultured human erythrocytes. PLoS One 9:e106924
Lee, Y Terry; Kim, Ki Soon; Byrnes, Colleen et al. (2013) A synthetic model of human beta-thalassemia erythropoiesis using CD34+ cells from healthy adult donors. PLoS One 8:e68307
Lee, Y Terry; de Vasconcellos, Jaira F; Yuan, Joan et al. (2013) LIN28B-mediated expression of fetal hemoglobin and production of fetal-like erythrocytes from adult human erythroblasts ex vivo. Blood 122:1034-41
Meier, Emily Riehm; Byrnes, Colleen; Weissman, Maxine et al. (2011) Expression patterns of fetal hemoglobin in sickle cell erythrocytes are both patient- and treatment-specific during childhood. Pediatr Blood Cancer 56:103-9

Showing the most recent 10 out of 12 publications