Faculty and staff

Prof. Linda Chia-Hui Yu

Linda Chia-Hui YuProf.

  • Linda Chia-Hui Yu

  • Title(s)：Prof.
  • Education:Ph.D., McMaster University, Canada
  • Expertise：Gastrointestinal Physiology
  • Phone：886-(02)23123456 ext. 288237
  • E-mail：lchyu@ntu.edu.tw

ACADEMIC POSITIONS
2016-current
Professor, Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan

2011-2016
Associate Professor, Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan

2005-2011
Assistant Professor, Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan

EDUCATION AND TRAINING
2002-2005
Post-doctoral Fellow, Department of Biological Science, University of Calgary, Calgary, Alberta, Canada

1997-2002
Ph.D., Programme of Physiology and Pharmacology, Department of Medical Sciences, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada

1995-1997
M.Sc., Department of Biology, Faculty of Science, University of Waterloo, Waterloo, Ontario, Canada

1990-1995
B.Sc., Department of Veterinary Medicine, College of Agriculture, National Taiwan University, Taipei, Taiwan

1995
D.V.M., Licensed Doctor of Veterinary Medicine, Taiwan

RESEARCH FIELD OF INTEREST
Our laboratory investigates pathophysiological mechanisms of intestinal epithelial biology and mucosal immuno-oncology. The research interest is focused on host-microbe interaction for regulation of epithelial barrier function and tumorigenesis in the gastrointestinal tract. Epithelial dysfunction and microbiota dysbiosis may lead to mucosal inflammation, and play crucial roles in the pathogenesis of various gastrointestinal diseases, such as inflammatory bowel disease, irritable bowel syndrome, and colorectal cancer. We identified a transient surge in microbiota diversity and virulence emergence correlated to altered antimicrobial transcriptomes in mouse colon during cancer initiation. Moreover, invasive pathobionts were isolated from colonic epithelial cells that triggered mucosal inflammation and tumor growth in the recipient mice through manipulating epithelial antimicrobial responses via autophagy suppression and free radical overproduction. Our findings revealed the key time frame and core mechanisms of intestinal microbiota driving host cancer progression.

RESEARCH TOPICS
Gastrointestinal immunophysiology, Microbiota, Host-microbe interaction, Epithelial barrier, Inflammatory bowel disease, Irritable bowel syndrome, Colorectal cancer, Metagenomic sequencing, Bacterial 16S rDNA sequencing, Gene microarray.

LABORATORY TECHNIQUES

  1. Animal models: Genetic mutant and transgenic mice, chemical-induced colorectal cancers, inflammatory bowel disease, psychological stress, bacterial infection.
  2. Primary cell cultures and cell lines: Intestinal epithelial cell and immune cell lines, co-cultures, primary intestinal organoid and spheroid cultures.
  3. Intestinal function and morphology tests: Epithelial electrophysiology and permeability assays, analysis of bacterial translocation, disaccharidase activity assay, cell cycle analysis, cell apoptosis and necroptosis assays, DNA damage assays, neutrophil activation and free radical production, cytokine detection, histological examination, epithelial cell isolation.
  4. Molecular techniques: Plasmid construction, RNA and DNA extraction, PCR, gene knockdown by siRNA and lentiviral-medited shRNA, site-directed mutagenesis, transfection and transformation.
  5. Bacterial and microbiota analysis: Aerobic and anaerobic culturing, single or multiple gene knockouts, bacteria-epithelial cocultures, gentamycin resistance assays, 16S rDNA sequencing analysis.
  6. Biochemical tests and imaging techniques: Western blotting, immunoprecipitation, immunofluorescent imaging, flow cytometry analysis and sorting, fluorescent in situ hybridization, confocal microscopic analysis.
  7. Special equipment: Ussing chamber systems, electrovoltemeter, thermocycler, hypoxic chamber, fluorescent microscope equipped with digital camera, microcentrifuge, shaking incubator, microtome.

HONORS AND AWARDS
2022-2025 Council member of International Union of Physiological Sciences (IUPS)

2019-2023 Council member of Federation of Asian and Oceanian Physiological Societies (FAOPS)

2022-2024 Innovative Research Grant, Three-year project, National Health Research Institute (NHRI), Taiwan

2020-2022 Director of International Affairs and Physiology Education Committee (IAPEC), Chinese Physiological Society (CPS), Taiwan

2020-2022 Standing director and Council member of Chinese Physiological Society (CPS), Taiwan

2016-2024 Council member, the 24th, 25th, 26th, 27th Council Board of the Chinese Physiological Society (CPS), Taiwan

2019 The 16th National Innovative Award and Taiwan SPARK Awardee

2019-2021 MAGIC Add-on grant, Ministry of Science and Technology (MoST), Taiwan

2019-2021 Innovative Research Grant, Three-year project, National Health Research Institute (NHRI), Taiwan

2017  Taiwan SPARK Awardee, Stanford SPARK pitch and Bio-Investor Forum candidate team, California, USA

2016-2018 Innovative Research Grant, Three-year project, Principle Investigator, National Health Research Institute (NHRI), Taiwan

2013-2016 Outstanding Young Investigator Project Grant, Three-year project, Principle Investigator, Ministry of Science and Technology (MoST), Executive Yuan, Taiwan.

2011-2014 National Research Program for Biopharmaceuticals (NRPB) Project Grant, Three-year project, Principle Investigator, Ministry of Science and Technology (MoST), Executive Yuan, Taiwan.

2015 Cover art of the issue selected by the journal Tissue Barriers.

2013 Original article selected as ‘Key Scientific Article’ in Global Medical Discovery, Ontario, Canada.

2014-2007 Academic Research Bursary, National Taiwan University

2011 Young Investigator Award, The 7th Federation of the Asian and Oceanian Physiological Society Congress (FAOPS) 2011

2009 Young Investigator Award, Asia Pacific Digestive Week (APDW) 2009

2005 Banff Inflammation Workshop Trainee Bursary and Best Poster Presentation Award, University Calgary, Banff, Alberta, Canada

2004 Mucosal Inflammation Research Group Trainee Travel Prize, University of Calgary, Nitric oxide Cytokines, and Inflammation International Symposium, Rio de Janeiro, Brazil

2003 Young Investigator Prize, Banff Inflammation Workshop 2003, Banff, AB, Canada

SOCIETY MEMBERSHIPS AND SERVICES

Chinese Physiological Society (CPS) (since 2005) : The 24th, 25th, 26th, 27th Society Council Member (since 2016)

American Physiology Society (APS) (since 2003) : Member

American Gastroenterology Association (AGA) (since 2008) : AGA Fellowship (since 2017)

PUBLICATIONS(* as corresponding author)

  1. Huang CY, Pai YC, and Yu LCH*. (2022) Glucose conferred irinotecan chemoresistance through divergent actions of pyruvate and ATP in cell death and proliferation of colorectal cancer. Oncology. doi:10.1159/000525977.
  2. Chang WY, Yang YT, She MP, Tu CH, Lee TC, Wu MS, Sun CH, Hsin LW, and Yu LCH*. (2022) 5-HT7 receptor-dependent intestinal neurite outgrowth contributes to visceral hypersensitivity in irritable bowel syndrome. Laboratory Investigation. doi: 10.1038/s41374-022-00800-z.
  3. Yu LCH, Wei SC, Li YH, Lin PY, Chang XW, Weng JP, Shue YW, Lai LC, Wang JT, Jeng YM, and Ni YH. (2022) Invasive pathobionts contribute to colon cancer initiation by counterbalancing epithelial antimicrobial responses. Cellular and Molecular Gastroenterology and Hepatology. 13(1):57-79. doi: 10.1016/j.jcmgh.2021.08.007.
  4. Huang YJ, Lee TC, Pai YC, Lin BR, Turner JR, and Yu LCH*. (2021) A Novel Tumor Suppressor Role of Myosin Light Chain Kinase Splice Variants through Downregulation of the TEAD4/CD44 Axis. Carcinogenesis. 42(7):961-974. doi: 10.1093/carcin/bgab038
  5. Chang CK, Chiu PF, Yang HY, Juang YP, Lai YH, Lin TS, Hsu LC, Yu LCH, Liang PH. (2021) Targeting Colorectal Cancer with Conjugates of a Glucose Transporter Inhibitor and 5-Fluorouracil.  Journal of Medicinal Chemistry. 64(8):4450-4461. doi: 10.1021/acs.jmedchem.0c00897. 
  6. Chen YH, Shin JY, Wei HM, Lin CC, Yu LCH, Liao WT, Chen DC, and Chu CL. (2021) Prevention of Dextran Sulfate Sodium-induced Mouse Colitis by a Fungal Protein Ling Zhi-8 via Promoting the Barrier Function of Intestinal Epithelial Cells. Food and Function. 12(4):1639-1650. doi: 10.1039/d0fo02604b.
  7. Pai YC, Weng LT, Wei SC, Wu LL, Shih DQ, Targan SR, Turner JR, and Yu LCH*. (2021) Gut microbial transcytosis induced by tumor necrosis factor-like 1A-dependent activation of a myosin light chain kinase splice variant contributes to IBD. Journal of Crohn’s and Colitis. 15(2): 258-272. doi: 10.1093/ecco-jcc/jjaa165
  8. Huang CY and Yu LCH*. (2020) Distinct patterns of IL-12/23 and TNFα synthesis by activated macrophages is modulated by glucose and colon cancer metabolites. Chinese Journal of Physiology. 63: 7-14
  9. Pai YC and Yu LCH*. (2020) Is ‘Cholinergic’ Stimulus Useful for Ulcerative Colitis Treatment?  Digestive Diseases and Sciences. 65(1):6-8. DOI: 10.1007/s10620-019-05933-8
  10. Huang CY, Huang CY, Pai YC, Lin BR, Lee TC, Liang PH, and Yu LCH*. (2019) Glucose metabolites exert opposing roles in tumor chemoresistance. Frontiers in Oncology. 9: 1282. DOI: 10.3389/fonc.2019.01282
  11. Huang YJ, Pai YC, and Yu LCH*. (2018) Host-microbiota interaction and intestinal epithelial functions under circadian control: implications in colitis and metabolic disorders. Chinese Journal of Physiology. 61(6):325-340.
  12. Yu LCH*. (2018) Microbiota dysbiosis and barrier dysfunction in inflammatory bowel disease and colitis-associated colorectal cancers: exploring a common ground hypothesis. Journal of Biomedical Sciences. 25(1): 79. doi: 10.1186/s12929-018-0483-8.
  13. Chang YY, Yu LCH, Yu IS, Jhuang YL, Huang WJ, and Jeng YM *. (2018) Deletion of cadherin-17 enhances intestinal permeability and susceptibility to intestinal tumour formation. Journal of Pathology. 246(3):289-299. doi: 10.1002/path.5138
  14. Yu LCH, Wei SC, and Ni YH*. (2018) Impact of Microbiota in Colorectal Carcinogenesis: Lessons from Experimental Models. Intestinal Research. 16(3):346-357. doi: 10.5217/ir.2018.16.3.346.
  15. Lee TC, Huang YC, Lu YC, Yeh YC, and Yu LCH*. (2017) Hypoxia-induced intestinal barrier changes in balloon-assisted enteroscopy. Journal of Physiology. 596 (15): 3411-3424. doi:10.1113/JP275277
  16. Pai YC and Yu LCH*. (2017) Transcytotic passage of intestinal bacteria across epithelial cells under proinflammatory stress. Internal Medicine Review. In press.
  17. Wei SC, Yang HF, Tsao PN, Weng MT, Yu LCH, Lai LC, Hsiao JH, Chuang EY, Shun CT, Ni YH, Shieh MJ, Wang CY, Xavier RJ, Podolsky DK, Yen JJY, Wong JM*. (2017) SHANK3, a novel Crohn’s disease-associated gene, regulates ZO-1 expression via protein kinase C epsilon. Inflammatory Bowel Disease. 23(10):1730-1740. doi: 10.1097/MIB.0000000000001250.
  18. Yu LCH, Wei SC, Ni YH*. (2017) Interplay between the gut microbiota and epithelial innate signaling in colitis-associated colon carcinogenesis. Cancer Research Frontiers. 3(1): 1-28. doi: 10.17980/2017.1
  19. Lu YZ, Huang CY, Huang YC, Lee TC, Kuo WT, Pai YC, and Yu LCH*. (2017) Tumor necrosis factor α-dependent neutrophil priming prevents intestinal ischemia/reperfusion-induced bacterial translocation. Digestive Diseases and Sciences. 62(6), 1498-1510. doi: 10.1007/s10620-017-4468-3. 
  20. Huang CY, Pai YC, Yu LCH*. (2017) Glucose-mediated cytoprotection in gut epithelium under ischemic and hypoxic stress. Histology and Histopathology. Nov 8:11839. doi: 10.14670/HH-11-839.
  21. Yeh YC, Yu LCH, Wu CY, Cheng YJ, Chao A, Chan WS, Hsu YC, Lee CT, Shih CC, Sun WZ, Tsai JC, Lin TY*. (2017) Effects of Endotoxin Absorber Hemoperfusion on Microcirculation in Septic Pigs. Journal of Surgical Research. 211:242-250. doi: 10.1016/j.jss.2016.12.026.
  22. Huang CY, Kuo WT, Huang CY, Lee TC, Chen CT, Peng WH, Lu KS, Yang CY, and Yu LCH*. (2017) Distinct cytoprotective roles of pyruvate and ATP by glucose metabolism on epithelial necroptosis and crypt proliferation in ischemic gut. Journal of Physiology. 595(2):505-521. doi: 10.1113/JP272208.
  23. Yu LCH*. (2016) Glucose protection mediated by glycolytic pyruvate but not ATP against ischemia-induced enterocyte cell death. Adaptive Medicine. 8(4): 167-172
  24. Hsu LT, Hung KY, Wu HW, Liu WW, She MP, Lee TC, Sun CH, Yu WH, Buret AG, Yu LCH*. (2016) Gut-derived cholecystokinin contributes to visceral hypersensitivity via nerve growth factor-dependent neurite outgrowth. Journal of Gastroenterology and Hepatology. 31(9):1594-603. doi: 10.1111/jgh.13296.
  25. Kuo WT, Lee TC, Yu LCH*. (2016) Janus-faced bacterial regulation of epithelial cell death and survival: association with colon carcinogenesis. Molecular and Cellular Oncology 2015; 3:1, e1029064. doi: 10.1080/19382014.2015.1024405
  26. Yang PJ, Yang WS, Nien HC, Chen CN, Lee PH, Yu LCH*, Lin MT*. (2015) Duodenojejunal bypass leads to altered gut microbiota and strengthened epithelial barriers in rats. Obesity Surgery. In press. doi: 10.1007/s11695-015-1968-0.
  27. Huang CY, and Yu LCH*. (2015) Pathophysiological mechanisms of death resistance in colorectal carcinoma. World Journal of Gastroenterology. 21 (41): 11777-92.
  28. Yu LCH*. (2015) Commensal bacterial internalization by epithelial cells: an alternative portal for gut leakiness. Tissue Barriers. 3: 3, e1008895.  doi: 10.1080/21688370.2015.1008895
  29. Kuo WT, Lee TC, Yang HY, Chen CY, Au YC, Lu YZ, Wu LL, Wei SC, Ni YH, Lin BR, Chen Y, Tsai YH, Kung JT, Sheu F, Lin LW , and Yu LCH*. (2015, Jan) LPS receptor subunits have antagonistic roles in epithelial apoptosis and colonic carcinogenesis. Cell Death & Differentiation 22 (10): 1590–1604. doi: 10.1038/cdd.2014.240.
  30. Yu LCH, Shih YA, Wu LL, Lin YD, Kuo WT, Peng WH, Lu KS, Wei SC, Ni YH*. (2014) Enteric dysbiosis promotes antibiotic-resistant bacterial infection: systemic dissemination of resistant and commensal bacteria through epithelial transcytosis. American Journal of Physiology: Gastrointestinal and Liver Physiology. 307 (8): G824-G835
  31. Wu LL, Peng WH, Kuo WT, Huang CY, Ni YH, Lu KS, Turner JR, and Yu LCH*. (2014) Commensal bacterial endocytosis in epithelial cells is dependent on myosin light chain kinase-activated brush border fanning by interferon-gamma. American Journal of Pathology 184(8):2260-74.
  32. Chen TL, Chen H, Wu HW, Lee TC, Lu YZ, Wu LL, Ni YH, Sun CH, Yu WH, Buret AG, Yu LCH*. (2013) Persistent gut barrier damage and commensal bacterial influx following eradication of Giardia infection in mice. Gut Pathogens 5: 26. Doi:10.1186/1757-4749-5-26.
  33. Huang CY, Kuo WT, Huang YC, Lee TC, and Yu LCH*. (2013) Resistance to hypoxia-induced necroptosis is conferred by glycolytic pyruvate scavenging of mitochondrial superoxide in colorectal cancer cells. Cell Death & Disease. 2013 May 2;4:e622.
  34. Lu YZ, Wu CC, Huang YC, Huang CY, Yang CY, Lee TC, Chen CF, Yu LCH*. (2012) Neutrophil priming by hypoxic preconditioning protects against epithelial barrier damage and enteric bacterial translocation in intestinal ischemia/reperfusion. Laboratory Investigation 92, 783-796
  35. Yu LCH, Wang JT, Wei SC, Ni YH*. (2012) Host-microbial interactions and regulation of intestinal epithelial barrier function: from physiology to pathology. World Journal of Gastrointestinal Pathophysiology. 3(1): 27-43
  36. Yu LCH*. (2012) Intestinal Epithelial Barrier Dysfunction in Food Hypersensitivity. Journal of Allergy, vol. 2012, Article ID 596081, doi:10.1155/2012/596081.
  37. Wu LL, Chiu HD, Peng WH, Lin BR, Lu KS, Lu YZ, and Yu LCH*. (2011) Epithelial inducible nitric oxide synthase causes bacterial translocation by impairment of enterocytic tight junctions via intracellular signals of Rho-associated kinase and protein kinase C zeta. Critical Care Medicine. 39, 2087–2098
  38. Huang CY, Hsiao JK, Lu YZ, Lee TC and Yu LCH*. (2011) Anti-apoptotic PI3K/Akt signaling by sodium/glucose transporter 1 reduces epithelial barrier damage and bacterial translocation in intestinal ischemia. Laboratory Investigation. 91, 294-309
  39. Yu LCH*. (2010) Protective mechanism against gut barrier dysfunction in mesenteric ischemia/reperfusion. Adaptive Medicine. 2 (1): 11-20
  40. Lee TC, Wang HP, Chiu HM, Lien WC, Chen MJ, Yu LCH, Sun CT, Lin JT, and Wu MS. (2010) Male Gender and Renal Dysfunction are Predictors of Adverse Outcome in Non-postoperative Ischemic Colitis Patients. Journal of Clinical Gastroenterology 44(5):e96-100.
  41. Wu CC, Lu YZ, Wu LL and Yu LCH*. (2010) Role of myosin light chain kinase in intestinal epithelial barrier defects in a rat model of bowel obstruction. BMC Gastroenterology.10, 39-50
  42. Hsiao JK, Huang CY, Lu YZ, Yang CY, and Yu LCH*. (2009) Magnetic resonance imaging detects intestinal barrier dysfunction in a rat model of acute mesenteric ischemia/reperfusion injury. Investigative Radiology. 44(6):329-35.
  43. Yu LCH*. (2009) The Epithelial Gatekeeper Against Food Allergy. Pediatrics and Neonatology. 50(6): 247-254
  44. Lin BR, Hsieh HT, Lee JM, Lai IR, Chen CF, Yu LCH*. (2008) Luminal hydrochloric acid stimulates rapid transepithelial ion fluxes in rodent esophageal stratified squamous epithelium. Journal of Physiology and Pharmacology. 59(3), 525-42
  45. Yu LCH, Huang CY, Kuo WT, Sayer H, Turner JR, Buret AG. (2008) SGLT-1-mediated glucose uptake protects human intestinal epithelial cells against Giardia duodenalis -induced apoptosis. International Journal of Parasitology. 38(8-9), 923-934
  46. Yu LCH, Turner JR, Buret AG. (2006) LPS/CD14 activation triggers SGLT-1-mediated glucose uptake and cell rescue in intestinal epithelial cells via early apoptotic signals upstream of caspase-3. Experimental Cell Research. 312(17), 3276-3286
  47. Yu LCH, Flynn AN, Turner JR, Buret AG. (2005) SGLT-1-mediated glucose uptake protects intestinal epithelial cells against LPS-induced apoptosis and barrier defect: a novel cell rescue mechanism? FASEB Journal. 19(13), 1822-35
  48. Montagnac G, Molla-Herman A, Bouchet J, Yu LCH, Conrad DH, Perdue MH, Benmerah A. (2005) Intracellular Trafficking of CD23: Differential Regulation in Humans and Mice by Both Extracellular and Intracellular Exons. Journal of Immunology 174(9), 5562-72.
  49. Montagnac G, Yu LCH, Bouchet J, Bevilacqua C, Conrad DH, Perdue MH, and Benmerah A.  (2005) Differential role for CD23 splice forms in apical to basolateral transcytosis of IgE/allergen complexes. Traffic 6(3), 230-42.
  50. Scott KG-E, Yu LCH and Buret AG. (2004). The role of CD8+ and CD4+ T lymphocytes in jejunal mucosal injury during murine giardiasis. Infection and Immunity 72 (6), 3536-3542
  51. Yu LCH, Montagnac G, Yang PC, Conrad DH, Benmerah A, and Perdue MH. (2003) Intestinal epithelial CD23 mediates enhanced antigen transport in allergy: evidence for novel splice forms. American Journal of Physiology Gastrointestinal and Liver Physiology. 285(1), G223-34.
  52. Yu LCH, Yang PC, Berin MC, Conrad DH, McKay DM, Satoskar AR and Perdue MH. (2001) Enhanced transepithelial antigen transport in intestine of allergic mice is mediated by IgE/CD23 and regulated by IL-4. Gastroenterology 121, 370-381
  53. Yu LCH and Perdue MH. (2001) Role of mast cells in intestinal mucosal function: studies in models of hypersensitivity and stress. Immunological Review. 179, 61-73
  54. Yu LCH and Perdue MH. (2001) Immunologically mediated transport of ions and macromolecules. Annals of New York Academic Science 915, 247-259
  55. Yang PC, Berin MC, Yu LCH, Perdue MH. (2001) Mucosal pathophysiology and inflammatory changes in rat small intestine during the late phase of the allergic reaction. American Journal of Pathology 158, 681-690
  56. Yang PC, Berin MC, Yu LCH, Conrad DH, and Perdue MH. (2000) Enhanced intestinal transepithelial antigen transport in allergic rats is mediated by IgE and CD23 (FceRII). Journal of Clinical Investigation 106, 879-886