Guey-Shin Wang, Ph.D.
Postdoctoral fellow
Funding: American Heart Association, Texas Affiliate
gw1@bcm.tmc.edu
713-798-5021
Joined the lab: April, 2005
Research Interests
Myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by a CTG trinucleotide expansion in the 3¹ untranslated region of the DMPK gene. The RNA gain-of-function hypothesis proposes that mutant DM transcripts containing expanded CUG tracts alter the function and localization of alternative splicing regulators, which are critical for normal RNA processing. In order to study the mechanism by which expanded repeats alter the regulation of pre-mRNA alternative splicing in vivo, we have developed a transgenic mouse model in which expression of DMPK CUG-repeat RNA is induced using a Cre-loxP approach. Cell-specific expression of DMPK CUG repeat RNA is induced by crosses with cell-specific Cre mouse lines. My project focuses on the mechanism of cardiac pathogenesis in DM1 using a heart-specific Cre line to express expanded CUG RNA in heart. I hope with this model, we could provide more insight on how alternative splicing is mis-regulated by CUG repeat RNA as well as how those RNA splicing regulators such as CUBGP1, ETR3 and MBNL involved in DM pathogenesis.
Publications
Wang, G.S. and Cooper T.A. (2007) Splicing in disease: disruption of the splicing code and the decoding machinery. Nature Rev. Genet. 8, 749-761.
Wang, G.S., Kearney, D.L., De Biasi, M., Taffet, G.E., and Cooper, T.A. (2007) Elevated CUGBP1 is an early event in an inducible heart-specific mouse model of myotonic dystrophy. J. Clin. Invest. 117, 2802-2811.
Lin CW, Huang TN, Wang GS, Kuo TY, Yen TY, Hsueh YP. Neural activity- and development-dependent expression and distribution of CASK interacting nucleosome assembly protein in mouse brain. J Comp Neurol. 2006 Feb 494(4):606-19.
Wang TF, Ding CN, Wang GS, Luo SC, Lin YL, Ruan Y, Hevner R, Rubenstein JL, Hsueh YP. Identification of Tbr-1/CASK complex target genes in neurons. J Neurochem. 2004 Dec 91(6):1483-92.
Wang GS*, Hong CJ, Yen TY, Huang HY, Ou Y, Huang TN, Jung WG, Kuo TY, Sheng M, Wang TF, Hsueh YP*. Transcriptional modification by a CASK-interacting nucleosome assembly protein. Neuron. 2004 Apr 42(1):113-28. (*equal contribution)
Wang GS, Chang NC, Wu SC, Chang AC. Regulated expression of alpha2B adrenoceptor during development. Dev Dyn. 2002 Oct 225(2):142-52.