Sickle cell anemia (SCA), one of the most common single gene disorders and hemoglobinopathies worldwide, is caused by a homozygous mutation in codon 6 of the beta globin gene. This mutation causes an amino acid change, glutamic acid to valine that changes normal adult hemoglobin (HbA) to sickle hemoglobin (HbS). When HbS becomes deoxygenated, it polymerizes and causes deformed, sickle-looking red blood cells that lyse, obstruct blood vessels, and reduce blood flow and oxygen delivery to tissues. Patients with SCA have multiple clinical problems, including vaso-occlusion, which causes acute painful episodes, organ damage, anemia and increased mortality. Fetal hemoglobin (HbF) is the main hemoglobin in the fetus, but its levels decline after birth to less than 1% in adults. However, there are individuals who continue to have high levels of HbF well into adulthood. Patients with SCA and high HbF have milder symptoms as HbF inhibits the polymerization of HbS. Some of the variation in HbF among patients can be accounted for by differences in three major quantitative trait loci (QTL) associated with high HbF. However, these QTLs only account for up to 10-50% of HbF variance. Long noncoding RNAs (lncRNAs) are recently described non-protein coding transcripts greater than 200 nucleotides and are involved in gene regulation. I propose to characterize one possible lncRNA transcribed from the region of a well-characterized QTL on chromosome 6q23 in CD34+-derived erythroid cells. I will also look for other lncRNAs associated with HbF gene expression in iPSC-derived erythroid cells from patients with SCA with a wide range of HbF concentrations and different genetic backgrounds. I will determine which lncRNAs are associated with HbF variance and follow this with studies to determine how lncRNA(s) regulate expression of HbF. Determining other factors associated with high HbF levels is critical in understanding the regulation of HbF expression and finding new therapeutic targets to induce HbF production.

Public Health Relevance

The purpose of this research project is to find other reasons why some people with sickle cell anemia have few to no symptoms. The results from this research project will help us to better understand the disease, and lead scientists to develop better drugs for people with sickle cell anemia.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Predoctoral Individual National Research Service Award (F31)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Klauzinska, Malgorzata
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Boston University
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Morrison, Tasha A; Wilcox, Ibifiri; Luo, Hong-Yuan et al. (2018) A long noncoding RNA from the HBS1L-MYB intergenic region on chr6q23 regulates human fetal hemoglobin expression. Blood Cells Mol Dis 69:1-9