Our current interest is to understand regulations of fetal to adult hemoglobin switching, which may lead to development of novel therapeutics for treating beta-hemoglobinopathies, including sickle cell anemia and beta-thalassemia. Towards this end, we use molecular, cellular, multi-omics, and genome editing methodologies to investigate in-depth molecular mechanisms of gamma-globin repression. Understanding these mechanistic details would provide clues whereby we might therapeutically induce fetal hemoglobin synthesis to treat beta-hemoglobinopathies. Two therapeutic strategies that we are currently investigating are:

      1) Repurposed drugs and small molecules that can inhibit cofactors with enzymatic activities necessary for repression of fetal hemoglobin

      2) Genetic-based approaches: CRISPR/Cas9 genome editing, short hairpin RNA

1.Nualkaew T, Khamphikham P, Pongpaksupasin P, Kaewsakulthong W, Songdej D, Paiboonsukwong K, Sripichai O, Engel JD, Hongeng S, Fucharoen S, Jearawiriyapaisarn N. UNC0638 induces high levels of fetal hemoglobin expression in beta-thalassemia/HbE erythroid progenitor cells. Ann Hematol. 2020;99(9):2027-36.

2.Khamphikham P, Nualkaew T, Pongpaksupasin P, Kaewsakulthong W, Songdej D, Paiboonsukwong K, Engel JD, Hongeng S, Fucharoen S, Sripichai O, Jearawiriyapaisarn N. High-level induction of fetal haemoglobin by pomalidomide in beta-thalassaemia/HbE erythroid progenitor cells. Br J Haematol. 2020;189(6):e240-e5.

3.Le CQ, Myers G, Habara A, Jearawiriyapaisarn N, Murphy GJ, Chui DHK, Steinberg MH, Engel JD, Cui S. Inhibition of LSD1 by small molecule inhibitors stimulates fetal hemoglobin synthesis. Blood. 2019;133(22):2455-9.

4.Yu L, Jearawiriyapaisarn N, Lee MP, Hosoya T, Wu Q, Myers G, Lim KC, Kurita R, Nakamura Y, Vojtek AB, Rual JF, Engel JD. BAP1 regulation of the key adaptor protein NCoR1 is critical for gamma-globin gene repression. Genes Dev. 2018;32(23-24):1537-1549.

5.Lee MP, Tanabe O, Shi L, Jearawiriyapaisarn N, Lucas D, Engel JD. The orphan nuclear receptor TR4 regulates erythroid cell proliferation and maturation. Blood. 2017;130(23):2537-47.