Tina Gao, Ph.D.
Started in the lab: September 2011
Funding: Postdoctoral Fellowship, Myotonic Dystrophy Foundation
Myotonic dystrophy 1 (DM1) is the most common muscular dystrophy of adult onset that is caused by the expanded CTG triplets at the 3'UTR of the DMPK gene. When transcribed into RNA, the expanded triplets in DMPK causes the RNA to become trapped in the nucleus. The nuclear accumulated CUG-expanded (CUGexp) RNA disrupts important splicing regulators, including MBNL1 and CELF1, resulting in splicing misregulation that is directly associated with clinical features of DM1 such as myotonia and insulin resistance. Currently, there is no effective treatment for DM1. Since the nuclear accumulation of CUGexp RNA is the predominant cause of DM1, targeting CUGexp RNA is attractive aim for DM1 treatment. I plan to test and develop RNAi and antisense approaches using adeno-associated virus (AAV) as a delivery tool in DM1 mouse models. These approaches have the potential to be translated for clinical application in DM1 patients.
Gao Z, Godbout R. Reelin-Disabled-1 signaling in neuronal migration: splicing takes the stage. Cell Mol Life Sci. 2012 Sep 28. [Epub ahead of print]
Gao Z, Poon S, Li L, Li X, Palmesino E, Glubrecht D, Colwill K, Dutta I, Kania A, Pawson T, Godbout R. Splice-mediated motif switching regulates Disabled-1 phosphorylation and SH2 domain interactions. Mol Cell Biol. 2012; 32(14): 2794-808
Katyal S, Glubrecht D, Li L, Gao Z, Godbout R. Disabled-1 alternative splicing in human fetal retina and neural tumors. PLoS ONE. 2011;6(12):e28579.
Gao Z, Godbout R. Serine phosphorylation regulates Disabled-1 early isoform turnover independently of Reelin. Cell Signal. 2011; 23(3):555-65.
Gao Z, Monckton EA, Glubrecht DD, Logan C, Godbout R. The Early Isoform of Disabled-1 Functions Independently of Reelin-mediated Tyrosine Phosphorylation in Chick Retina. Mol Cell Biol. 2010; 30(17):4339-53.
Liu RZ, Mita R, Beaulieu M, Gao Z, Godbout R. Fatty acid binding proteins in brain development and disease. Int J Dev Biol. 2010; 54(8-9):1229-39.
Katyal S, Gao Z, Monckton E, Glubrecht D, Godbout R. Hierarchical Disabled-1 tyrosine phosphorylation in Src-family kinase activation and neurite formation. J Mol Biol. 2007; 368(2):349-64.
Katyal S, Gao Z, Liu R, Godbout R. Evolutionary conservation of alternative splicing in chicken. Cytogenet Genome Res. 2007; 117(1-4):146-57.