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分類清單
姜為中
姜為中
職稱助理教授
學歷Ph.D., Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, U.S.A.
經歷:Post-doctoral researcher, Center for Autophagy Research, UT-Southwestern Medical Center, Dallas, Texas, U.S.A
辦公室: 生物醫學大樓 五樓 R506 室
電話:886-2-2826-7127
Email: wchiang@ym.edu.tw
學經歷
2018 迄今   

國立陽明大學 生化暨分子生物研究所 助理教授

2013-2018

Center for Autophagy Research, UT-Southwestern Medical Center 美國西南醫學中心 細胞自噬研究中心 博士後研究員

2012

Department of Molecular and Integrative Physiology, University of Michigan 美國密西根大學 生理學研究所博士

榮譽
2019 

沈力揚教授基金會 講師級研究與進修獎助

2019 

國立陽明大學醫學院 學生網路教學評估優良教師

2014-2018     

Centers of Excellence for Translational Research (CETR) Traineeship

指導學生獲獎
2019             

指導郭靖榮獲台灣粒線體學會年會 優秀論文壁報獎

專利與技轉
專利名稱

Small molecule inducers of autophagy that function by disrupting Beclin 1/ Bcl-2 binding (細胞自噬誘發小分子藥物)

發明人

Jef DeBrabander, Qiren Liang, Beth Levine, Wei-Chung Chiang (姜為中)
US provision Filing No.:62680578 (Filing Date: 2018年6月4日)

技轉

Casma Therapeutics

專長--選擇性自噬作用 (selective autophagy)、粒線體自噬(mitophagy)與相關疾病研究
研究方向
當細胞面對環境壓力(如養分缺乏、缺氧)等不利因素時,細胞能夠啟動許多促進環境適應的機制以確保存活。其中一種機制--自噬作用 (autophagy)為幫助細胞在不利環境下存活的重要反應。
Autophagy 意為細胞 ”自食” 的現象:Auto-源自於希臘文的”自 (self)”;phagy意指 ”吃 (eat)”。這種作用是細胞對於自己的胞內物質(大如胞器,小如蛋白質、脂質)進行回收分解的機制。如果將細胞比方成一座大城市,每日的車水馬龍的運作持續的造成城市各處堆積了許多垃圾或是損壞的物件。若不予以清除將很快對城市運作造成影響。自噬作用就像是城市的垃圾車、資源回收以及銷毀系統。如同大城市一般,細胞內可藉由自噬體 (autophagosome)-如同資源回收車一般來運送損壞或是多餘的胞器、不正常的的蛋白質或甚至是入侵的微生物。最終,自噬體將貨物(cargo)載往溶酶體 (lysosome)-細胞的垃圾處理場進行分解。這整個過程稱為「自噬作用」。此現象對於細胞生存是一個關鍵的機制。
過去二十多年的研究發現了自噬作用其實能夠透過某些辨認方式,選擇性的降解特定胞內物質,這樣的過程稱為選擇性自噬作用 (selective autophagy)。它扮演著胞內蛋白質與胞器恆定 (organellar homeostasis)、品質管控、或是胞內固有免疫 (intracellular innate immunity)中決定性的角色。包括粒線體、過氧化體 (peroxisome)、蛋白聚集體 (protein aggregates)、細菌、病毒或是半衰期長之蛋白質(long-lived proteins)等胞內結構都會被選擇性自噬清除。參與這項機制的基因若突變即可能影響這些胞內物質或入侵病原體的正常清除,而引起老化、神經系統退化疾病、癌症、或感染疾病。因此,了解選擇性細胞自噬的機制,即可能找到這些疾病的有效療法。
Macroautophagy (hereafter referred to as autophagy) is a catabolic pathway by which cells sequester unwanted or damaged cellular proteins or organelles through a double membrane structure called the autophagosome. This process is mediated by a set of evolutionarily conserved genes, the autophagy-related (ATG) genes, which function in nucleation of the autophagosomal membrane, elongation of the autophagic membrane, sequestration of cytoplasmic constituents, and lysosomal degradation of the sequestered contents.
Selective autophagy is a homeostatic quality control process that targets specific cytoplasmic components to autophagosomes for lysosomal destruction. Diverse cargos have been identified as substrates for selective autophagy, including mitochondria (mitophagy), peroxisomes (pexophagy), endoplasmic reticulum (ERophagy), and viruses (virophagy). Mitophagy is the major pathway by which eukaryotic cells eliminate damaged or unwanted mitochondria as damaged mitochondria release reactive oxygen species (ROS), leading to inflammasome activation, genotoxic stress, promotion of tumorigenesis and aging. Defects in mitophagy are implicated in neurodegenerative diseases such as Parkinson’s disease, Alzheimer disease, and age-related pathologies. Thus, the proper removal of mitochondria is essential for organismal health in diverse eukaryotic species.
The primary research focus of our laboratory is to understand the molecular regulation and biological functions of mitophagy. A fundamental question in the autophagy field remains how cargos such as mitochondria are selectively targeted for autophagic degradation. We will use series of genetic, cell biology, biochemical approaches to understand the mechanisms that confer substrate selectivity in mitophagy and investigate the pathological consequences of mitophagy dysfunction in diseases using model organisms such as C. elegans and mice. These studies may guide future efforts in developing therapeutic options against age-related and neurodegenerative diseases and pave the way for the development of new treatments for patients with diseases associated with mitochondrial dysfunction.
研究著作

Álvaro F. Fernández, Salwa Sebti, Yongjie Wei, Zhongju Zou, Mingjun Shi, Kathryn McMillan, Congcong He, Tabitha Ting, Yang Liu, Wei-Chung Chiang, Denise Marciano, Gabriele Schiatarella, Govind Bhagat, Orson W. Moe, Ming-Chang Hu and Beth Levine. Disruption of the beclin 1-BCL2 autophagy regulatory complex promotes longevity in mice.Disruption of the beclin 1/Bcl-2 autophagy regulatory complex promotes longevity in mice. Nature. 558 (7708) 136-140 (2018).

 

Wei-Chung Chiang, Yongjie Wei, Yi-Chun Kuo, Shuguang Wei, Anwu Zhou, Zhongju Zou, Jenna Yehl, Matthew J. Ranaghan, Adam Skepner, Joshua A. Bittker, Jose R. Perez, Bruce A. Posner and Beth Levine. High Throughput Screens to Identify Autophagy Inducers that Function by Disrupting Beclin 1/Bcl-2 Binding. ACS Chem Biol. (2018). doi: 10.1021/acschembio.8b00421.

 

Yongjie Wei*, Wei-Chung Chiang*, Rhea Sumpter Jr., Prashant Mishra and Beth Levine. Prohibitin 2 is an Inner Mitochondrial Membrane Mitophagy Receptor. Cell. 168(1-2) 224-238 (2017). (*co-first author)

 

Wei-Chung Chiang, Tsui-Ting Ching, Hee-Chul Lee, Carol Mousigian and Ao-Llin Hsu. HSF-1 regulators DDL-1/2 link insulin-like signaling to heat-shock responses and modulation of longevity. Cell. 148(1) 322-334 (2012).

 

Wei-Chung Chiang, Daniel X. Tishkoff, Bo Yang, Joshua Wilson-Grady, Xiaokun Yu, Travis Mazer, Mark Eckersdorff, Steven P. Gygi, David B. Lombard, and Ao-Lin Hsu. C. elegans SIRT6/7 Homolog SIR-2.4 Promotes DAF-16 Relocalization and Function during Stress. PLoS Genetics, 8(9): e1002948.

 

Tsui-Ting Ching, Wei-Chung Chiang, Ching-Shih Chen and Ao-Lin Hsu. Celecoxib Extends Worm Lifespan Independent of COX-2 Inhibition. Aging Cell. 10(3):506-19 (2010).

 

Mu-Hwa Yang, Wei-Chung Chiang, Shyue-Yih Chang, Po-Min Chen and Kou-Juey Wu. Increased NBS1 expression as a prognostic marker of aggressive head and neck cancer and overexpression of NBS1 contributes to transformation. Clin. Cancer Res. 12, 507-515 (2006).

 

Yen-Chung Chen, Yi-Ning Su, Po-Chien Chou, Wei-Chung Chiang, Ming-Cheng Chang, Liang-Shun Wang, Shu-Chun Teng and Kou-Juey Wu. Overexpression of NBS1 contributes to transformation through the activation of phosphatidylinositol 3-kinase/Akt. J. Biol. Chem. 280, 32505-11 (2005).

 

Shih-Hung Yu, Wei-Chung Chiang, Hsiu-Ming Shih and Kou-Juey Wu. Stimulation of c-Rel transcriptional activity by PKA catalytic subunit beta. J. Mol. Med. 82(9):621-8 (2004).

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