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徐志文博士

長聘副研究員
  • 886-2-2652-3070 (Lab) (Room No: N603)
  • 886-2-2782-7654 (Fax)
Specialty:

(Host defense & Mucosal immunity)

(Lysosome dysfunction)

(Colitis pathogenesis)

 

Education and Positions:

  • (M.S. in Immunology, National Taiwan University)

    (Ph.D. in Immunology, Baylor College of Medicine, USA)

    (Postdoc/Instructor, La Jolla Institute for Immunology, USA)

研究簡介

溶酶體 (Lysosome) 對細胞自噬降解作用,扮演了重要角色。細胞自噬作用崩潰會造成內質網壓力, 細胞凋亡, 或細胞變質, 因而導致病變, 如發炎性腸道疾病(IBD)或溶酶體貯積病(LSD)。已知許多神經系統疾病, 包括C型尼曼匹克氏症, 巴金森氏症, 和阿茲海默症, 都是與溶酶體失常的相關疾病, 因此皆可視為一種溶酶體貯積病。臨床上許多溶酶體貯積病的病變風險基因, 也都證實會增加罹患發炎性腸道疾病, C型尼曼匹克氏症,或帕金森氏症的機會。舉例來說, Npc1 基因突變, 與克隆氏症 (一種發炎性腸道疾病)或巴金森症候群的同時發生, 有密切關聯。而 Lrrk2 基因多型性, 也是造成發炎性腸道疾病(IBD)及巴金森氏症的原因之一。我們最近發表了半乳糖凝集素-9 (Galectin-9), 一種醣結合蛋白同時也是腸道克隆氏症的風險基因, 可調控小腸潘氏細胞 (Paneth cells)及胰臟腺泡細胞 (acinar cells) 內溶酶體及細胞自噬功能, 藉此來防止腸道及胰臟發炎。因此, 溶酶體的稳定功能對細胞自噬作用旺盛的細胞, 如小腸潘氏細胞, 胰臟腺泡細胞, 及嗜中性白血球(neutrophils), 極為重要, 尤其是防止這些細胞功能失常而導致病變。此論點解釋了為何病人因溶酶體失常而導致的發炎性腸道疾病, 與胰臟發炎, 嗜中性白血球缺乏症(neutropenia) , 脂肪肝炎, 神經退化疾病, 有病理上的共通關聯。

研究目標

本實驗室藉由分子及細胞分析層次, 利用我們最近建立的溶酶體動物模型 (Nat Commun 11:4286, Aug 2020), 來研究腸道表皮細胞內溶酶體功能失常如何導致多重(器官)病變。具體來說, 我們聚焦研究小腸內專門抗菌的潘氏細胞(一種表皮細胞)的溶酶體崩潰, 是如何造成微生物菌叢(microbiota)失調?  而這樣的失調, 又是如何導致脂肪肝 (腸與肝的調控軸)及巴金森氏症(腸與腦的調控軸) 的發生? 支持此論點的研究, 包括腸道發炎與脂肪肝生成有相關, 以及腸道微生物菌叢和巴金森氏症病發有密切關聯。

進行中的研究

- 腸與肝的調控軸:溶酶體中的醣基化藉由調控胞內膽固醇來促進腸道防禦及預防脂肪肝

- 腸與腦的調控軸:腸道抗菌的潘氏細胞透過調控微生物菌叢來預防巴金森氏症病

期刊 26 專書 0

  1. GY Seo, D Takahashi, Q Wang, Z Mikulski, A Chen, TF Chou, P Marcovecchio, S McArdle, A Sethi, (JW Shui), M Takahashi, CD Surh, H Cheroutre, and M Kronenberg. Epithelial HVEM maintains intraepithelial T cell survival and contributes to host protection. Science Immunology 7, eabm6931 (2022-07) [JCR] [WOS]
  2. K Geevimaan, JY Guo, CN Shen, JK Jiang, CS J. Fann, MJ Hwang, (JW Shui), HT Lin, MJ Wang, HC Shih, A FY Li, SC Chang, SH Yang, and JY Chen. Patient-derived organoid serves as a platform for personalized chemotherapy in advanced colorectal cancer patients. Frontiers in Oncology 12, 883437 (2022-06) [JCR] [WOS]
  3. C Stienne, RV Slane, L Elmen, M Veny, S Huang, J Nguyen, E Chappell, MO Balmert, (JW Shui), MA Hurchla, M Kronenberg, SN Peterson, KM Murphy, CF Ware, and JR Sedy. Btla signaling in conventional and regulatory lymphocytes coordinately tempers humoral immunity in the intestinal mucosa. Cell Reports 38, 110553 (2022-03) [JCR] [WOS]
  4. HY Chiang, HH Lu, JN Sudhakar, YW Chen, NS Shih, YT Weng, and (JW Shui*). IL-22 initiates an IL-18-dependent epithelial response circuit to enforce intestinal host defense. Nature Communications 13, 874 (2022-02) [JCR] [WOS]
  5. JN Sudhakar, HH Lu, HY Chiang, CS Suen, MJ Hwang, SY Wu, CN Shen, YM Chang, FA Li, FT Liu, and (JW Shui*). Luminal Galectin-9-Lamp2 interaction promotes lysosome stabilization and facilitates autophagy to prevent pathogenesis in the pancreas and intestine. Nature Communications 11, 4286 (2020-08) [JCR] [WOS]
  6. MA Mintz, JH Felce, MY Chou, V Mayya, Y Xu, (JW Shui), J An, Z Li, A Marson, T Okada, CF Ware, M Kronenberg, ML Dustin, and JG Cyster. The HVEM-BTLA axis restrains T cell help to germinal center B cells and functions as a cell-extrinsic suppressor in lymphomagenesis. Immunity 51, 310 (2019-08) [JCR] [WOS]
  7. TWH Tang, HC Chen, CY Chen, CYT Yen, CJ Lin, RP Prajnamitra, LL Chen, SC Ruan, JH Lin, PJ Lin, HH Lu, CW Kuo, CM Chang, AD Hall, EI Vivas, (JW Shui), P Chen, TA Hacker, FE Rey, TJ Kamp, and PCH Hsieh. Loss of gut microbiota alters immune system composition and cripples postinfarction cardiac repair. Circulation 139, 647 (2019-01) [JCR] [WOS]
  8. D Glal, JN Sudhakar, HH Lu, MC Liu, HY Chiang, YC Liu, CF Cheng, and (JW Shui*). ATF3 sustains IL-22-induced STAT3 phosphorylation to maintain mucosal immunity through inhibiting phosphatases. Frontiers in Immunology 9, 2522 (2018-11) [JCR] [WOS]
  9. GY Seo, (JW Shui), D Takahashi, C Song, Q Wang, K Kim, Z Mikulski, S Chandra, DA Giles, S Zahner, PH Kim, H Cheroutre, M Colonna, and M Kronenberg. LIGHT-HVEM signaling in innate lymphoid cell subsets protects against enteric bacterial infection. Cell Host & Microbe 24, 249 (2018-08) [JCR] [WOS]
  10. R Herro, (JW Shui), S Zahner, D Sidler, Y Kawakami, T Kawakami, K Tamada, M Kronenberg, and M Croft. LIGHT-HVEM signaling in keratinocytes controls development of dermatitis. Journal of Experimental Medicine 215, 415 (2018-01) [JCR] [WOS]
- More Publications-

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- 學生 -
Chen, Yu-Wen
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