นที เจียรวิริยะไพศาล

     Our current focus is to develop molecular therapeutic approaches for treatment of ß-thalassemia, a disorder of deficient production of ß-globin chain and hemoglobin A (α2ß2). Severe cases of ß-thalassemia result in pronounced anemia, bone deformities, hepatosplenomegaly and, if left untreated, death. Current treatment consists of regular, lifelong blood transfusions combined with iron chelation therapy. Allogeneic bone marrow transplantation, the only cure, is not available to most patients. It has been well known that the pathophysiology of ß-thalassemia is mainly due to accumulation of excess unmatched α-globin chains, which precipitate in red cell precursors leading to cell death, ineffective erythropoiesis and severe anemia. Therefore, we aim to use the molecular-based approaches to reduce the excess unmatched α-globin chains, which would restore the balance of α-/ß-globin ratio and ameliorate the ß-thalassemia phenotypes. These approaches include:

1. Downregulation of α-globin gene expression by lentiviral-delivered short hairpin RNA (shRNA)

2. Upregulation of ß-globin gene expression by

2.1 Splice-switching therapy to correct aberrant pre-mRNA splicing caused by ß-globin mutations

2.2 Engineered Nucleases to mediate site-specific correction of ß-globin mutations

We hope that these studies will lead to novel curative treatment for ß-thalassemia.

Selected Publications

1. Tubsuwan A, Munkongdee T, Jearawiriyapaisarn N, Boonchoy C, Winichagoon P, Fucharoen S, Svasti S*. Molecular analysis of globin gene expression in different thalassaemia disorders: individual variation of beta(E) pre-mRNA splicing determine disease severity. British journal of haematology. 2011;154(5):635-43. Epub 2011/07/08.

2. Jearawiriyapaisarn N, Moulton HM, Sazani P, Kole R, Willis MS*. Long-term improvement in mdx cardiomyopathy after therapy with peptide-conjugated morpholino oligomers. Cardiovascular research. 2010;85(3):444-53. Epub 2009/10/10.

3. Moulton HM*, Wu B, Jearawiriyapaisarn N, Sazani P, Lu QL, Kole R. Peptide-morpholino conjugate: a promising therapeutic for Duchenne muscular dystrophy. Annals of the New York Academy of Sciences. 2009;1175:55-60. Epub 2009/10/03.

4. Bauman J, Jearawiriyapaisarn N, Kole R*. Therapeutic potential of splice-switching oligonucleotides. Oligonucleotides. 2009;19(1):1-13. Epub 2009/01/08.

5. Jearawiriyapaisarn N, Moulton HM, Buckley B, Roberts J, Sazani P, Fucharoen S, Iversen, P.L., Kole, R*. Sustained dystrophin expression induced by peptide-conjugated morpholino oligomers in the muscles of mdx mice. Molecular therapy : the journal of the American Society of Gene Therapy. 2008;16(9):1624-9. Epub 2008/06/12.

Full Publications

1. Janpipatkul K, Suksen K, Borwornpinyo S, Jearawiriyapaisarn N, Hongeng S, Piyachaturawat P, Chairoungdua A*. Downregulation of LAT1 expression suppresses cholangiocarcinoma cell invasion and migration. Cellular signalling. 2014;26(8):1668-79. Epub 2014/04/15.

2. Tubsuwan A, Munkongdee T, Jearawiriyapaisarn N, Boonchoy C, Winichagoon P, Fucharoen S, Svasti S*. Molecular analysis of globin gene expression in different thalassaemia disorders: individual variation of beta(E) pre-mRNA splicing determine disease severity. British journal of haematology. 2011;154(5):635-43. Epub 2011/07/08.

3. Jearawiriyapaisarn N, Moulton HM, Sazani P, Kole R, Willis MS*. Long-term improvement in mdx cardiomyopathy after therapy with peptide-conjugated morpholino oligomers. Cardiovascular research. 2010;85(3):444-53. Epub 2009/10/10.

4. Moulton HM*, Wu B, Jearawiriyapaisarn N, Sazani P, Lu QL, Kole R. Peptide-morpholino conjugate: a promising therapeutic for Duchenne muscular dystrophy. Annals of the New York Academy of Sciences. 2009;1175:55-60. Epub 2009/10/03.

5. Bauman J, Jearawiriyapaisarn N, Kole R*. Therapeutic potential of splice-switching oligonucleotides. Oligonucleotides. 2009;19(1):1-13. Epub 2009/01/08.

6. Jearawiriyapaisarn N, Moulton HM, Buckley B, Roberts J, Sazani P, Fucharoen S, Iversen, P.L., Kole, R*. Sustained dystrophin expression induced by peptide-conjugated morpholino oligomers in the muscles of mdx mice. Molecular therapy : the journal of the American Society of Gene Therapy. 2008;16(9):1624-9. Epub 2008/06/12.