Dr. Wang, Guey-Shin 王桂馨 博士

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Dr. Wang, Guey-Shin
王桂馨 博士

Assistant Research Fellow
助研究員

Specialty:
  • Cardiovascular disease
  • Neurodegeneration
  • Neurodevelopmental disorder

RESEARCH

The laboratory is interested in the mechanism of cardiac and neural pathogenesis in myotonic dystrophy type 1 (DM1). DM1 is the most common form of adult-onset muscular dystrophy, is dominantly inherited and affects multiple tissues with symptoms including myotonia, muscle wasting, cataract, conduction defect, cardiomyopathy, daytime somnolence and psychiatric disorders. DM1 is caused by a CTG trinucleotide expansion in the 3』 untranslated region of the DMPK gene. DMPK mRNA containing CUG repeats accumulates in nuclear foci and affect nuclear and cytoplasmic activities of RNA binding proteins such as muscleblind like 1 (MBNL1) and CUGBP1 and ETR-3 like factor (CELF) proteins. The resulting sequestration of MBNL1 and PKC-mediated up-regulation of CELF1 cause the mis-regulated alternative splicing, translation and mRNA stability. Cardiovascular disease is the second most common cause of death in individuals with DM1 accounting for ~30% of fatalities. The occurrence of cognitive and behavioral impairment in individuals with DM1 is high. However, the mechanisms of causing the cardiac and neural deficits are remained unknown. We have established mouse models for investigating how cardiac and neural phenotypes are developed. We will primarily focus on (1) the pathogenesis of heart failure, (2) the molecular mechanism of neurodegeneration in adult-onset DM1 mouse model, and (3) the molecular mechanism of developmental disorders in congenital DM1 mouse model. 

研究介紹

本實驗室的研究主題為探究「肌強直型肌肉萎縮症」所造成之心血管及中樞神經系統疾病之致病機轉。肌強直型肌肉萎縮症為一顯性遺傳疾病,患者具有肌肉強直、心血管系統及神經系統方面之疾病。造成疾病的主要原因是由於,數百或上千之CTG repeat 位在DMPK 基因 3』 UTR,經轉錄成RNA之後形成穩定之二級結構,此RNA累積在細胞核內影響細胞之生理功能。 本實驗室已成功建立心臟專一 (heart-specific) 及中樞神經系統專一 (brain-specific) 之小鼠模式:(1) 960 CTG表現在心臟,小鼠具有心律不整進而導致心臟衰竭;(2) 960 CTG若表現在出生後成鼠之神經細胞,小鼠具有神經退化疾病; 若表現在發育中之神經細胞,小鼠則具有神經發育的問題。我們期望:透過研究「肌強直型肌肉萎縮症」在心血管與神經系統的致病機轉,可以進而瞭解廣泛的心臟衰竭或是神經發育,神經退化形成的原因。對於,心臟衰竭,神經發育問題,或是神經退化的成因提供另一個重要的研究方向與工具。

 

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