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Dr. Shui, Jr-Wen

Associate Research Fellow
  • 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)


Research Overview

Lysosome plays a key role in autophagic degradation in cells. The breakdown of autophagy causes ER stress, apoptosis, or cell degeneration that is linked to disease pathogenesis such as inflammatory bowel disease (IBD) in the gut or lysosomal storage disorder (LSD). It is known that many neurological diseases, including Niemann-Pick Type C (NPC) disease, Parkinson disease (PD), and Alzheimer disease (AD), are caused by lysosome dysfunction and thus considered as one form of LSD. Clinically, many risk factors for LSD are also contributing to pathogenesis of IBD, NPC, or PD. For example, mutation of the Npc1 gene is associated with Crohn’s disease (a form of IBD) and Parkinsonism. Gene polymorphism of Lrrk2 is involved in IBD and PD. We recently reported that Galectin-9, a carbohydrate-binding protein and a risk gene for Crohn disease, controls lysosome function and autophagy in gut Paneth cells and pancreatic acinar cells to prevent colitis and pancreatitis, respectively. Therefore, stable lysosome function is crucial for autophagy-active cell types, such as gut Paneth cells, pancreatic acinar cells, and neutrophils, thereby preventing autophagy breakdown and consequent pathogenesis. This explains why IBD is linked to many types of pathological manifestations caused by lysosome dysfunction, including pancreatitis, neutropenia, infection, fatty liver, and neurodegeneration.  

Research Goal of the lab is to elucidate how lysosome dysfunction contributes to organ pathogenesis at the molecular and cellular levels, in the context of the lysosomal model that we have recently established (Nat Commun 11:4286, Aug 2020). Specifically, we study how the lysosomal breakdown of anti-microbial Paneth cells in the gut contributes to microbiota disruption, and how this breakdown causes the development of fatty liver (the gut-to-liver axis) and Parkinson disease (the gut-to-brain axis). Supporting this, intestinal dysbiosis or inflammation is associated with the progression of steatohepatitis, cirrhosis, and Parkinsonism.

Ongoing Research

a) Lysosomal N-glycosylation controls cholesterol egress to facilitate host defense and prevent steatohepatitis.

b) Gut Paneth cell dysfunction contributes to the development of Parkinson disease via microbiota dysbiosis.

Journal 26 Book 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]

- POSTDOC -
Sudhakar, Janaki N
Sudhakar, Janaki N
- RESEARCH ASSOCIATES -
Chiang, Hung-Yu
Chiang, Hung-Yu
Weng, Yi-Ting
Weng, Yi-Ting
- STUDENTS -
Chen, Yu-Wen
Chen, Yu-Wen
- ALUMNI -
Lu, Hsueh-Han
Lu, Hsueh-Han