Our Research Program

Our laboratory has been working on the mechanisms responsible for gene expression in erythroid-lineage cells and our target disorders are sickle cell disease and beta-thalassemia. We have been focusing on two projects. The first one focuses on identifying intracellular signaling pathways that are involved in the regulation of fetal globin gene expression. We recently began studying the role of cyclic nucleotides and alpha-synuclein on fetal hemoglobin expression. The second project is the study of the molecular mechanism by which expression of the human beta-like globin genes are regulated during development. We will characterize cis-acting elements as well as transcription factors.

Publications

  • Kuroyanagi Y, Kaneko Y, Muta K, Park B-S, Moi P, A, Ausenda S, Cappellini M D, & Ikuta T. (2006) cAMP differentially regulates γ-globin gene expression in erythroleukemic cells and primary erythroblasts through c-Myb expression. Biochemical & Biophysical Research Communications 344:1038-1047.

  • Bailey L, Kuroyanagi Y, Penteado C, Conran N, Costa FF, Ausenda S, Cappellini MD, & Ikuta T. (2007) Expression of the γ-globin gene in β-thalassemia is sustained by the cAMP signaling pathway. British Journal of Haematology 138:382-395.

  • Conran N, Saad ST, Costa FF, & Ikuta T. (2007) Leukocyte numbers correlate with plasma levels of granulocyte-macrophage colony-stimulating factor in sickle cell disease. Annals of Hematology 86:246-251.

  • Suzuki Y, Takeda Y, & Ikuta T. (2008) Immunoblotting conditions for human hemoglobin chains. Analytical Biochemistry. 378:218-220.

  • Giuseppina M, Porcu L, Asunis I, Giuseppina LI, Ristaldi MS, Porcu S, Ikuta T, Cao A, & Moi P. (2010) Regulation of the human HBA genes by KLF-4 erythroid cell lines. British Journal of Haematology 149:748-758.

  • Head CA, Swerdlow PS, McDade WA, Joshi RM, Ikuta T, Cooper ML, & Eckman JR. (2010) Beneficial effects of nitric oxide breathing in adult patients with sickle cell crisis. American Journal of Hematology 85:800-802. 

  • Gutsaeva DR, Parkerson JB, Yerigenahally SD, Kurz JC, Schaub RG, Ikuta T, & Head CA. (2011) Anti-P-selectin aptamer inhibits adhesion of sickle red blood cells and leukocytes to endothelial cells in sickle cell mice. Blood 117:727-735.

  • Ikuta T, Adekile AD, Gutsaeva DR, Parkerson JB, Yerigenahally SD, Clair B, Kutlar B, Odo N, & Head CA. (2011) The proinflammatory cytokine GM-CSF downregulates fetal hemoglobin expression by attenuating the cAMP-dependent pathway in sickle cell disease. Blood Cells, Molecules, and Diseases 47:235-242.

  • Gutsaeva DR, Montero-Huerta P, Parkerson JB, Yerigenahally SD, Ikuta T, & Head CA. (2014) Molecular mechanisms underlying synergistic adhesion of sickle red blood cells by hypoxia and low nitric oxide bioavailability. Blood 123(12):1917-1926.

  • Ghoshal P, Rajendran M, Odo N, & Ikuta T. (2014) Glycosylation inhibitors efficiently inhibit P-selectin-mediated cell adhesion to endothelial cells. PLoS One 9(6):e999363.

  • Ikuta T, Sellak H, Odo N, Adekile AD, Gaensler KML. Nitric oxide-cGMP signaling stimulates erythropoiesis through multiple lineage-specific transcription factors: clinical implications and a novel target for erythropoiesis. PLOS ONE 2016 Jan;11(1): e0144561.

Current Funding Sources

Ikuta T, Principal Investigator. Grant-in-Aid Award from the American Heart Association (Southeast Affiliate), 2015-2017

Future Studies and Long-term Goals

Our long-term goal is to develop new therapeutics for anemic disorders such as sickle cell disease and beta-thalassemia. We are specifically interested in the role of phosphodiesterases in regulating the expression of beta-like globin genes.

Location of Lab: CB-2618, 706-721-4812

Dr. Tohru Ikuta      
Tohru Ikuta, MD, PhD