Dr. Yan, Yu-Ting 顏裕庭 博士

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Dr. Yan, Yu-Ting
顏裕庭 博士

Associate Research Fellow
長聘副研究員

  • Ph.D., University of Medicine and Dentistry of New Jersey

  • 02-2789-9061 (Lab) (Room No: N616)
  • 02-2652-3941 (Office)
  • 02-2785-8847 (Fax)
  • yyan@ibms.sinica.edu.tw
Specialty:
  • Molecular Genetics
  • Cardiovascular Development 
  • Myofibrillogenesis

RESEARCH

The studies of Yan's laboratory are on the convergence of genetic and biochemical pathways to maintain the proteostasis in striated muscle and neural tissues. Proteostasis is referred to the biochemical network allowing for cellular proteins to maintain a proper biological activity according to the cell environment. It is mainly controlled by protein quality control (PQC) system. Disruption of PQC system will cause the derailment of cellular protein homeostasis and lead to the occurrence of diseases. The PQC is crucial for cardiac and neural health and requires the collaboration of all its components to be functional. It is composed of three systems including chaperone proteins, the ubiquitin-proteasome system (UPS), and autophagy. We currently focus on elucidating the molecular mechanism of small heart shock protein B7 (HSPB7) at maintaining the proteostasis in cardiac, muscular and neural health and possible therapeutical role at related diseases. At our recent studies, we showed that small heat shock protein B7 is required for maintaining FLNC location and normal function in muscle cells. Loss of HSPB7 causes overexpression and aggregation of FLNC in skeletal muscle. We also found that the expression of FLNC and HSPB7 is tightly associated with each other during muscle regeneration in mouse. In addition, HSPB7 interacts with dimerized FLNC in cell culture system. Put together, we propose the hypothesis that HSPB7 can play a role to facilitate the cell mechanosensor function by stabilizing structure of FLNC to maintain the muscle homeostasis. 

研究介紹

本研究室主要探討心肌及骨骼肌細胞臟相之生成和功能之維持,以及維持細胞白質恆定之相關疾病的發生機制。我們建立相關基因改造小鼠為人類疾病模型,用以探討人類相關疾病生成機制,並用以研發、檢測適當之疾病治療方法。目前主要研究方向專注於: (一)胚胎心肌細胞之生成發育: 我們專注於胚胎時期心肌前趨細胞之生成來源、分化以及塑型調節的分子機制之探討。其中熱休克蛋白HSPB7在胚胎發育過程中,對心肌細胞心肌肌小節生成之生化、生理功能的探討。(二)HSPB7對心肌細胞細絲蛋白C(FLNC)之生理功能、生化結構穩定之維持。多種不同的FLNC基因變異與數種心臟和肌肉疾病症狀有關,如肌原纖維肌病(MFM),心臟肥厚性病變,擴張型心肌病(HCM和DCM)和心律不整心肌病(ACM)。我們先前發現小鼠失去HSPB7基因造成FLNC在心臟或橫膈膜大量表現、沉積,並導致心臟肌肉傳導缺陷而心律不整或橫膈膜結構缺陷而呼吸衰竭致死,顯現出HSPB7對FLNC蛋白質表現和其功能恆定之維持之需要,以及對於FLNC相關遺傳疾病的治療可能扮演一個重要角色。目前實驗室研究是以基因治療於小鼠相關疾病模型,以檢測用予人類疾病治療之可能性。

 

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