Introduction

          Our laboratory studies the genetic bases of the intrinsic cell defense systems against pathogenic bacteria and their virulence factors. We apply chemical genomic, forward/reverse genetic, CRISPR/Cas9 genome editing, molecular and biochemical methodologies, and the model organism Caenorhabditis elegans to elucidate the conserved mechanisms in host-pathogen interactions. The advantage of using C. elegans as a host-pathogen model includes: 1) This organism has a short 2-3 weeks life span; 2) It has a relative small and fully sequenced genome which can facilitates genetic and genomic analysis; 3) A wealth of data has demonstrated that a variety of developmental, neurological, cell biological and biochemical processes have been highly conserved between this simple model organism and mammals. Moreover, a rapidly growing number of human and animal microbial pathogens have been shown to infect and kill C. elegans. In many cases, microbial genes known to be essential for full virulence in mammalian models have been shown to be similarly required for maximum pathogenicity. Since the innate immune responses are highly conserved among different organisms throughout evolution, understanding the molecular basis of the intrinsic cell defense systems in C. elegans should shed light onto some aspects of immunity in Human diseases.

研究主軸

本實驗室主要運用線蟲(C. elegans)作為模式生物，來研究致病細菌及其致病因子之病源與宿主間之交互作用(pathogen-host interaction)。我們主要運用：化學基因體學、遺傳學篩選、CRISPR/Cas9 基因體編輯、分子及生物化學等方法來探索病源與宿主交互作用之生物訊息傳遞以及致病機制。

線蟲被運用於分子生物學、細胞生物學、神經生物學與發育生物學之研究已有數十年之久，這個世紀以來已有兩組線蟲科學家因利用此一模式生物對計畫性細胞死亡(programmed cell death)及干擾性核醣核酸(RNA interference)生物機制的研究而獲頒諾貝爾生醫獎，以及研究在活體表現綠色螢光蛋白(Green fluorescent protein)的運用而獲得一次的諾貝爾化學獎的殊榮，顯示線蟲在尖端生物技術的開發與生命現象的深入探索，皆具有其他生物材料所不可取代的優勢。

近年來以線蟲作為模式生物來研究致病菌之致病機制也正快速發展中。在許多研究中發現，許多致病菌在感染哺乳類宿所需的致病因子，也同樣被用於對線蟲之致病過程，而且線蟲之細胞以及先天性免疫反應(innate immunity)也與哺乳類細胞具有很高的相似性。因為先天性免疫反應在演化的過程中具有相當高的保留性，我們相信經由對線蟲的研究或許我們可以對人類感染性疾病之免疫反應有更進一步的了解。

Selected Publications

1. Hui-Chen Hsieh, I-Hsiang Huang, Shao-Wen Chang, Po-Lin Chen, Yu-Cheng Su, Shuying Wang, Wei-Jiun Tsai, Ping-Hung Chen, Raffi V. Aroian, and Chang-Shi Chen. PRMT-7/PRMT7 activates HLH-30/TFEB to guard plasma membrane integrity compromised by bacterial pore-forming toxins. Autophagy. 2024 Feb 19:1-24.

2. Yi-Sheng Jiang, Cheng-Rung Huang, Chang-Shi Chen, and Jeng-Shiung Jan. GSH/pH-Sensitive Poly(glycerol sebacate dithiodiglycolate) Nanoparticle as a Ferroptotic Inducer through Cooperation with Fe3+. ACS Appl. Polym. Mater. 2024 Jan 10; (6):1129-1140.

3. Yu-Cheng Su, Ching-Chun Wang, Yi-Wei Chen, Sin-Tian Wang, Cing-Ying Shu, Pei-Jane Tsai, Wen-Chien Ko, Chang-Shi Chen, and Po-Lin Chen. Haemolysin Ahh1 secreted from Aeromonas dhakensis activates the NLRP3 inflammasome in macrophages and mediates severe soft tissue infection. International Immunopharmacology. 2024 Jan 4;128:111478.

4. Hui-Zhong Zhuang , Yu-Fon Chen , Ya-Chu Yu , Cheng-Rung Huang , Yi-Sheng Jiang , Chang- Shi Chen, and Jeng-Shiung Jan. Gelatin composite gel particles comprised of in-situ formed zinc oxide and silver nanoparticles with enhanced antibacterial activities via enzymatic degradation. Colloids Surf A Physicochem Eng Asp. 2023 Dec 5;678:132509.

5. Fang-Yu Chung, Cheng-Rung Huang, Chang-Shi Chen, and Yu-Fon Chen. Natural nanogels crosslinked with S-benzyl-L-cysteine exhibit potent antibacterial activity. Biomaterials Advances. 2023 Oct;153:213551. 

6. Zhi-Han Lin , Shun-Ya Chang , Wen-Chi Shen , Yen-Hung Lin , Chiu-Lun Shen, Sin-Bo Liao , Yu-Chun Liu , Chang-Shi Chen , Tsui-Ting Ching, and Horng-Dar Wang. Isocitrate Dehydrogenase Alpha-1 Modulates Lifespan and Oxidative Stress Tolerance in Caenorhabditis elegans. Int. J. Mol. Sci. 2022 Dec 29;24(1):612.

7. Dhrubajyoti Das, Hui-Chen Hsieh, Chang-Shi Chen, Wei-Long Chen, and Han-Sheng Chuang. Ultrafast and -Sensitive Screening of Pathogens by Functionalized Janus Microbeads Enabled Rotational Diffusometry in Combination with Isothermal Amplification. Small Science. 2022 Mar 3; 2200010.

8. Sin-Tian Wang, Cheng-Ju Kuo, Chih-Wen Huang, Tzer-Min Lee, Jenn-Wei Chen, and Chang-Shi Chen. OmpR coordinates the expression of virulence factors of enterohemorrhagic Escherichia coli in the alimentary tract of Caenorhabditis elegans. Molecular Microbiology. 2021 Jul;116(1):168-183. 

9. Chia-En Tsai, Fang-Jung Yang, Ching-Han Lee, Yen-Ping Hsueh, Cheng-Ju Kuo, and Chang-Shi Chen. The conserved regulator of autophagy and innate immunity hlh-30/TFEB mediates tolerance of enterohemorrhagic Escherichia coli in Caenorhabditis elegans. Genetics. 2021 Mar 3;217(1):1-17. 

10. Masayuki Hashimoto, Yi-Fen Ma, Sin-Tian Wang, Chang-Shi Chen, Ching-Hao Teng. Iron acquisition of urinary tract infection Escherichia coli involves pathogenicity in Caenorhabditis elegans. Microorganisms. 2021 Feb 2;9(2):310. 

11. Thi Thanh Huong Pham, Wan-Ying Huang, Chang-Shi Chen, Wen-Tai Chiu, and Han-Sheng Chuang. Effects of electrotactic exercise and antioxidant EUK-134 on oxidative stress relief in Caenorhabditis elegans. PLoS One. 2021 Jan 20;16(1):e0245474. 

12. Daniel J. Klionsky, and Chang-Shi Chen, et. al. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy. 2021 Jan;17(1):1-382. 

13. Cheng-Rung Huang, Cheng-Ju Kuo, Chih-Wen Huang, Yu-Ting Chen, Bang-Yu Liu, Chung-Ta Lee, Po-Lin Chen, Wen-Tsan Chang, Yun-Wen Chen, Tzer-Min Lee, Hui-Chen Hsieh, and Chang-Shi Chen. Host CDK1 and formin mediate microvillar effacement induced by enterohemorrhagic Escherichia coli. Nature Communications. 2021 Jan 4;12(1):90.

14. Cheng-Ju Kuo, Ya-Chu Hsu, Sin-Tian Wang, Bang-Yu Liou, Serene Boon-Yuean Lim, Yi-Wei Chen, and Chang-Shi Chen. IGLR-2, a leucine-rich repeat domain containing protein, is required for the host defense in Caenorhabditis elegans. Front Immunol. 2020 Nov 30;11:561337.

15. Yi-Wei Chen, Wen-Hsuan Yeh, Hung-Jen Tang, Jenn-Wei Chen, Hung-Yu Shu, Yu-Chen Su, Sin-Tian Wang, Cheng-Ju Kuo, Yin-Ching Chuang, Chi-Chung Chen, Wen-Chien Ko, Chang-Shi Chen, and Po-Lin Chen. UvrY Is Required for the Full Virulence of Aeromonas dhakensis. Virulence. 2020 May;11(1):502-520.

16. Wen-Chun Huang, Chung-Yen Lin, Masayuki Hashimoto, Jiunn-Jong Wu, Ming-Cheng Wang, Wei-Hung Lin, Chang-Shi Chen, and Ching-Hao Teng. The role of the bacterial protease Prc in the uropathogenesis of extraintestinal pathogenic Escherichia coli. J Biomed Sci. 2020 Jan 3;27(1):14.

17. Peter Brown, RELISH Consortium/Chang-Shi Chen, and Yaoqi Zhou. Large expert-curated database for benchmarking document similarity detection in biomedical literature search. Database (Oxford). 2019. doi:10.1093/database/baz085.

18. Han-Sheng Chuang, Wen-Hui Wang, and Chang-Shi Chen. Worms on a Chip. In: Tokeshi M. (eds) Applications of Microfluidic Systems in Biology and Medicine. Bioanalysis (Advanced Materials, Methods, and Devices), 7:151-196. Springer. 2019. doi:10.1007/978-981-13-6229-3_6.

19. Yi-Wei Chen, Wen-Chien Ko, Chang-Shi Chen, and Po-Lin Chen. Evaluating Virulence and Pathogenesis of Aeromonas Infection in a Caenorhabditis elegans Model. J Vis Exp. 2018 Dec 20;(142). doi: 10.3791/58768.

20. Ling-Hsien Tu, Ning-Hsuan Tseng, Ya-Ru Tsai, Yi-Wei Lo, Jien-Lin Charng, Hua-Ting Hsu, Yu-Sheng Chen, Rong-Jie Chen, Ying-Da Wu, Yi-Tsu Chan, Chang-Shi Chen, Jim-Min Fang, and Yun-Ru Chen. Rationally designed divalent amides inhibit amyloid-beta fibrillization, induce fibril dissociation, and ameliorate cytotoxicity. Eur J Med Chem. 2018 Oct 5;158:393-404.

21. Yi-Wei Chen, Wen-Chien Ko, Chang-Shi Chen*, and Po-Lin Chen*. RIOK-1 is a suppressor of the p38 MAPK innate immune pathway in Caenorhabiditis elegans. Front Immunol. 2018 Apr 17;9:774. *Corresponding authors.

22. Cheng-Ju Kuo, Sin-Tian Wang, and Chang-Shi Chen. Detection of Enterohemorrhagic Escherichia coli Colonization in Murine Host by Non-invasive In Vivo Bioluminescence System. J Vis Exp. 2018 Apr 9;(134). doi:10.3791/56169.

23. Cheng-Ju Kuo, Sin-Tian Wang, Chia-Mei Lin, Hao-Chieh Chiu, Cheng-Rung Huang, Der-Yen Lee, Geen-Dong Chang, Ting-Chen Chou, Jenn-Wei Chen, and Chang-Shi Chen. A multi-omic analysis reveals the role of fumarate in regulating the virulence of Enterohemorrhagic Escherichia coli. Cell Death Dis. 2018 Mar 7;9(3):381.

24. Chia-Wen Tsai, Rong-Tzong Tsai, Shih-Ping Liu, Chang-Shi Chen, Min-Chen Tsai, Shao-Hsuan Chien, Huey-Shan Hung, Shinn-Zong Lin, Woei-Cherng Shyu, and Ru-Huei Fu. Neuroprotective Effects of Betulin in Pharmacological and Transgenic C. elegans Models of Parkinson's Disease. Cell Transplant. 2017 Dec;26(12):1903-1918.

25. Jung-Chen Su, Yu-Ting Huang, Chang-Shi Chen, Hao-Chieh Chiu, Chung-Wai Shiau. Design and synthesis of malonamide derivatives as antibiotics against methicillin-resistant Staphylococcus aureus. Molecules. 2017 Dec 22;23(1).

26. Huan-Da Chen, Cheng-Yuan Kao, Bang-Yu Liu, Shin-Whei Huang, Cheng-Ju Kuo, Jhen-Wei Ruan, Yen-Hung Lin, Cheng-Rung Huang, Yu-Hung Chen, Horng-Dar Wang, Raffi V. Aroian, and Chang-Shi Chen. HLH-30/TFEB-mediated autophagy functions in a cell-autonomous manner for epithelium intrinsic cellular defense against bacterial pore-forming toxin in C. elegans. Autophagy. 2017 Feb;13(2):371-385.

27. Po-Lin Chen, Yi-Wei Chen, Chun-Chun Ou, Tzer-Min Lee, Chi-Jung Wu, Wen-Chien Ko, and Chang-Shi Chen. A disease model of muscle necrosis caused by Aeromonas dhakensis infection in Caenorhabiditis elegans. Front Microbiol. 2017 Jan 4;7:2058.

28. Cheng-Ju Kuo, Jenn-Wei Chen, Hao-Chieh Chiu, Ching-Hao Teng, Tai-I Hsu, Pei-Jung Lu, Wan-Jr Syu, Sin-Tian Wang, Ting-Chen Chou, and Chang-Shi Chen. Mutation of the enterohemorrhagic Escherichia coli core LPS biosynthesis enzyme RfaD confers hypersusceptibility to host intestinal innate immunity in vivo. Front Cell Infect Microbiol. 2016 Aug 12; 6:82.

29. Han-Sheng Chuang, Wan-Jung Kuo, Chia-Lin Lee, I-Hua Chu, and Chang-Shi Chen. Exercise in an electrotactic flow chamber ameliorates age-related degeneration in Caenorhabditis elegans. Sci Rep. 2016 Jun 16;6:28064.

30. Han-Chu Chang*, Yu-Ting Huang*, Chang-Shi Chen*, Yi-Wei Chen, Yu-Tsung Huang, Jung-Chen Su, Lee-Jene Teng, Chung-Wai Shiau, and Hao-Chieh Chiu. In vitro and in vivo activity of a novel sorafenib derivative SC5005 against MRSA. J Antimicrob Chemother. 2016 Feb;71(2):449-59. *Equal contribution.

31. Po-Lin Chen, Pei-Jane Tsai, Chang-Shi Chen, Ying-Chuan Lu, Hung-Mo Chen, Nan-Yao Lee, Ching-Chi Lee, Chia-Wen Li, Ming-Chi Li, Chi-Jung Wu, and Wen-Chien Ko. Aeromonas stool isolates from individuals with or without diarrhea in southern Taiwan: Predominance of Aeromonas veronii. J Microbiol Immunol Infect. 2015 Dec;48(6):618-24.

32. Hsiang Yu, Huey-Jen Lai, Tai-Wei Lin, Chang-Shi Chen*, and Szecheng John Lo*. Loss of DNase II function in the gonad is associated with a higher expression of antimicrobial genes in C. elegans. Biochem J. 2015 Aug 15;470(1):145-54.*Corresponding authors.

33. Po-Lin Chen, Chi-Jung Wu, Pei-Jane Tsai, Hung-Jen Tang, Nan-Yao Lee, Ching-Chi Lee, Chia-Wen Li, Ming-Chi Li, Chun-Chun Ou, Chang-Shi Chen*, and Wen-Chien Ko*. Virulence diversity among bacteremic Aeromonas isolates: ex vivo, animal, and clinical evidences. PLoS One. 2014 Nov 6;9(11):e111213. *Corresponding authors.

34. Ru-Huei Fu, Yu-Chi Wang, Chang-Shi Chen, Rong-Tzong Tsai, Shih-Ping Liu, Wen-Lin Chang, Hsin-Lien Lin, Chia-Hui Lu, Jing-Rong Wei, Zih-Wan Wang, Woei-Cherng Shyu, Shinn-Zong Lin. Acetylcorynoline attenuates dopaminergic neuron degeneration and α-synuclein aggregation in animal models of Parkinson’s disease. Neuropharmacology. 2014 Jul;82:108-20.

35. Po-Lin Chen, Chi-Jung Wu, Chang-Shi Chen, Pei-Jane Tsai, Hung-Jen Tang, and Wen-Chien Ko. A comparative study of clinical Aeromonas dhakensis and Aeromonas hydrophila isolates in southern Taiwan: A. dhakensis is more predominant and virulent. Clin Microbiol Infect. 2014 Jul;20(7):O428-34.

36. Ru-Huei Fu, Horng-Jyh Harn, Shih-Ping Liu, Chang-Shi Chen, Wen-Lin Chang, Yue-Mi Chen, Jing-En Huang, Rong-Jhu Li, Sung-Yu Tsai, Huey-Shan Hung, Woei-Cherng Shyu, Shinn-Zong Lin, Yu-Chi Wang. n-Butylidenephthalide Protects against Dopaminergic Neuron Degeneration and α-Synuclein Accumulation in Caenorhabditis elegans Models of Parkinson's Disease. PLoS One. 2014 Jan 8;9(1):e85305.

37. Han-Sheng Chuang, Hsiang-Yu Chen, Chang-Shi Chen, Wen-Tai Chiu. Immobilization of the Nematode Caenorhabditis elegans with Addressable Light-Induced Heat Knockdown (ALINK). Lab Chip. 2013 Jul 2;13(15):2980-9.

38. Ya-Luen Yang, Kah-Sin Loh, Bang-Yu Liou, I-Hua Chu, Cheng-Ju Kuo, Huan-Da Chen, and Chang-Shi Chen. SESN-1 is a positive regulator of lifespan in Caenorhabditis elegans. Exp Gerontol. 2013 Mar; 48(3):371-379.

39. Ting-Chen Chou, Hao-Chieh Chiu, Cheng-Ju Kuo, Ching-Ming Wu, Wan-Jr Syu, Wen-Tai Chiu, and Chang-Shi Chen. Enterohaemorrhagic Escherichia coli O157:H7 Shiga-like toxin 1 is required for full pathogenicity and activation of the p38 mitogen-activated protein kinase pathway in Caenorhabditis elegansin. Cell Microbiol. 2013 Jan;15(1):82-97.

40. Chi-Jung Wu, Hsuan-Chen Wang, Chang-Shi Chen, Hung-Yu Shu, Ai-Wen Kao, Po-Lin Chen, and Wen-Chien Ko. Genome Sequence of a Novel Human Pathogen, Aeromonas aquariorum. J Bacteriol. 2012 Aug;194(15):4114-5.

41. Chang-Shi Chen, Audrey Bellier, Cheng-Yuan Kao, Ya-Luen Yang, Huan-Da Chen, Ferdinand C O Los, and Raffi V. Aroian. WWP-1 is a novel modulator of the DAF-2 Insulin-like signaling network involved in pore-forming toxin cellular defenses in Caenorhabditis elegans. PLoS One. 2010 Mar 2;5(3):e9494.

42. Audrey Bellier, Chang-Shi Chen, Cheng-Yuan Kao, Hediye N. Cinar, and Raffi V. Aroian. Hypoxia and the Hypoxic Response Pathway Protect against Pore-Forming Toxins in C. elegans. PLoS Pathog. 2009 Dec;5(12):e1000689.

43. Xiang-Qian Li, Anderson Tan, Michael Voegtline, Senait Bekele, Chang-Shi Chen, and Raffi Aroian. Expression of Cry5B Protein from Bacillus thuringiensis in Plant Roots Confers Resistance to Root-Knot Nematode. Biological Control. 2008 Oct.; 47(1) 97-102.

Current members

PI: 

Dr. Chang-Shi Chen (陳昌熙)

Education: 

Bachelor of Science, National Taiwan University

Master of Science, National Yang-Ming University

Ph.D, The Ohio State University

Professional Experience:

Assistant Professor 2008~2013

Associate Professor 2013~2017

Professor 2017~2022

Distinguished Professor 2022~present

Postdoctoral Scholar:

黃晟榮 博士 (Dr. Cheng-Rung Huang) /成大基醫所

Ph.D Program:

謝惠臻 (Hui-Chen Hsieh) /成大醫技/成大生化

Master Program:

洪敏嫥 /成大醫技系

王宇禾 /海洋大學生科系

黃浤珅 /中山醫醫技系 

張韶文 /中國醫生技系

唐曉愛 /高雄大學生科系

李韋萱 /成大醫技系

陸智嵥 /中興食科系

Alumni

Ph.D

楊亞倫 博士 (Dr. Ya-Luen Yang) /成大基醫所

陳奐達 博士 (Dr. Huan-Da Chen) /中山海資/成大生化/成大基醫所

郭承儒 博士 (Dr. Cheng-Ju Kuo) /中山海資/成大生化/成大基醫所

陳怡偉 博士 (Dr. Yi-Wei Chen) /中山海資/成大基醫所

黃晟榮 博士 (Dr. Cheng-Rung Huang) /成大生化/成大基醫所

王信沺 博士 (Dr. Sin-Tian Wang) /嘉大微免/成大基醫所

Master of Science

陳奐達 /中山海資/成大生化

羅加俽 /高雄大學生技/成大生化

林高田 /中山醫大生技/成大生化

黃幸惠 /嘉大生農/成大生化

郭承儒 /中山海資/成大生化

周廷蓁 /中山海資/成大生化

劉邦渝 /成大生科/成大生化

林佳玫 /東海化學/成大生化

楊昉蓉 /中山生科/成大生化

廖聰羽 /中山海資/成大生化

陳緯學 /清大生科/成大生化

葉玟瑄 /中國醫醫技/成大生化

許雅筑 /中山生科/成大生化

林汶燕 /長庚醫技/成大生化

陳昱廷 /台南生技/成大生化

林依穎 /義守生技/成大生化

林叔樺 /慈濟分子生物暨人類遺傳學系/成大生化

黃智玟 /高醫醫技/成大生化

連佩怡 /慈濟分子生物暨人類遺傳學系/成大生化

陳鼎喬 /成大醫技/成大生化

楊又頲 /屏東大學應化系/成大生化

張欣慈 /慈濟分子生物暨人類遺傳學系/成大生化

蔡佳恩 /中興植物病理學系/成大生化

謝惠臻 /成大醫技/成大生化

黃億翔 /臺南大學生物科技學系/成大生化

楊采文 /中山醫大醫技系/成大生化

黃筠婷 /中興大學食品暨應用生物科技學系/成大生化

     伍思翰 /東海大學化學系/成大生化

陳美菁 /中山大學海資系/成大生化

瞿張伊 /海洋大學生科系/成大生化

鄭嫈蓉 /暨南大學應用化學系/成大生化

Research Assistant

盧益玄 /中山醫生技

何偉豪 /台大農化

徐建民 /高師大生科/成大生化

周廷蓁 /中山海資/成大生化

林佳玫 /東海化學/成大生化

許雅筑 /中山生科/成大生化

鍾佩璇/嘉大食科所

陳飛旭/國防微免所

蔡佳恩/中興植物病理學系/成大生化

Undergraduate:

張乃祐 /成大醫技

歐承泓 /成大醫技

劉襲民 /成大醫技

陳玲麗 /成大醫技

陳學平 /成大醫技

周姿函 /成大醫技

王鈺智 /成大醫學

傅蓓安 /成大醫學

陳柏堯 /成大醫技

黃涱煜 /成大醫技

陳鼎喬 /成大醫技

王     紳 /成大醫技

蕭玉朋 /成大醫技

林冠佑 /成大醫學

李宛霖 /成大醫學

廖顯祥 /成大醫學

Ting-Yu Chang /UCSD, Pharmacological Chemistry and Cognitive Science

陳姿諭 /成大醫技

沈筱蓉 /成大醫技

郭沁恩 /成大醫技

鍾昀蓁 /成大醫技

Contact Us

Dr. Chang-Shi Chen Lab

E-mail: cschen@mail.ncku.edu.tw

Address: 1 University Road, Tainan City 70101, Taiwan

Department of Biochemisty and Molecular Biology, National Cheng Kung University

Tel : (886)-6-2353535 Ext: 5548 (Office), 5678 (Lab.)

聯絡資訊

陳昌熙老師實驗室

電子郵件 : cschen@mail.ncku.edu.tw

地址 : 70101 臺南市東區大學路1號 國立成大醫學院 生化所

電話 : 06-235-3535 分機 5548 或 5678