Cell signaling pathways involved in drug-mediated fetal hemoglobin induction: Strategies to treat sickle cell disease

Betty S. Pace, Li Liu, Biaoru Li, Levi H. Makala

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


The developmental regulation of globin gene expression has shaped research efforts to establish therapeutic modalities for individuals affected with sickle cell disease and β-thalassemia. Fetal hemoglobin has been shown to block sickle hemoglobin S polymerization to improve symptoms of sickle cell disease; moreover, fetal hemoglobin functions to replace inadequate hemoglobin A synthesis in β-thalassemia thus serving as an effective therapeutic target. In the perinatal period, fetal hemoglobin is synthesized at high levels followed by a decline to adult levels by one year of age. It is known that naturally occurring mutations in the γ-globin gene promoters and distant cis-acting transcription factors produce persistent fetal hemoglobin synthesis after birth to ameliorate clinical symptoms. Major repressor proteins that silence γ-globin during development have been targeted for gene therapy in β-hemoglobinopathies patients. In parallel effort, several classes of pharmacological agents that induce fetal hemoglobin expression through molecular and cell signaling mechanisms have been identified. Herein, we reviewed the progress made in the discovery of signaling molecules targeted by pharmacologic agents that enhance γ-globin expression and have the potential for future drug development to treat the β-hemoglobinopathies.

Original languageEnglish (US)
Pages (from-to)1050-1064
Number of pages15
JournalExperimental Biology and Medicine
Issue number8
StatePublished - Aug 19 2015
Externally publishedYes


  • Fetal hemoglobin
  • NRF2
  • cell signaling
  • p38 MAPK
  • sickle cell disease
  • β-hemoglobinopathies

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


Dive into the research topics of 'Cell signaling pathways involved in drug-mediated fetal hemoglobin induction: Strategies to treat sickle cell disease'. Together they form a unique fingerprint.

Cite this