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周德盈 Chou, Teh-Ying

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Chou, Teh-Ying 周德盈
教授 /台北榮民總醫院病理檢驗部主任
教授 / 陽明大學臨床醫學研究所、
           生化暨分子生物研究所


 

Tel: 02-28757080
 
Education
2016 (expected)
1995
EMBA
 
Ph.D.
International Business
Biochemistry, Cellular and Molecular Biology Training Program
National Taiwan University College of Management, Taiwan
Johns Hopkins University School of Medicine
(Thesis Advisors: Gerald W. Hart and Chi V. Dang)
 
1984
M.D.
Medicine
National Yang-Ming University, Taiwan.
 
 
Academic appointments

2018-present

Professor, Brain Research Center, Tsing-Hua University

2018-present

Professor, Department of Biotechnology and Laboratory Science in Medicine, Yang-Ming

2013-2017

Director, Institute of Clinical Medicine, Yang-Ming University University

Director, Institute of Clinical Medicine, Yang-Ming University 

2014-present
2014-present
2013-present
2011-present
President, Taiwan Society of Pathology / Taiwan Division of International Academy of Pathology
Director, Doctoral Degree Program of Translational Medicine, Yang-Ming University
Director, Institute of Clinical Medicine, Yang-Ming University
Professor, Institute of Clinical Medicine, Yang-Ming University
2012-present
2006-2012
2004-2006
Chief, Molecular Pathology Division, Taipei Veterans General Hospital, Taiwan
Chief, Surgical Pathology Division, Taipei Veterans General Hospital, Taiwan
Chief, General Pathology Division, Taipei Veterans General Hospital, Taiwan
2001-2002
 
1999-2001
Calendar Binford Clinical Fellow, Department of Pulmonary and Mediastinal Pathology, Armed Forces Institute of Pathology (Supervisor: William D. Travis)
Resident, Anatomic Pathology, Washington University Medical Center/Barnes-Jewish Hospital
 
 
Honors
2010
Academic Prize for Excellent Research, Taipei Veterans General Hospital
2010
Best Clinical Teacher Award, Taipei Veterans General Hospital
2006
Outstanding Physician, Veterans Affairs Commission, Executive Yuan, Taiwan
1990-1993
National Science Council Scholar, Taiwan
 
RESEARCH INTERESTS
        As a diagnostic and molecular pathologist with basic research training experience, I have always been enthusiastic about the molecular mechanisms involved in pathogenesis of diseases. Recent years of subspecialty training and clinical practice in pulmonary pathology have in particular skewed my research interests towards understanding the pathogenesis of lung cancer, including its formation, progression, metastasis, as well as response to various therapeutic agents, at the molecular level. My research interests focus on Precision Medicine, Tumor Metastasis and Cancer Glycobiology:
 
(1)Precision medicine for lung cancer with emphasis on NGS and liquid biopsy: The management of lung cancer has evolved tremendously in the past decade resulting from the introduction of targeted therapy into the daily practice of thoracic oncologists. Beginning with EGFR-TKIs coupled with detecting activating mutations of EGFR, currently there are hundreds of molecules targeting specific tumor driver mutations waiting for clinical use approval. While 2nd and 3rd generation EGFR-TKIs have come to the market, drug resistance remains to be the major obstacles in cancer targeted therapy. To accurately use the right drug on the right patient at the right time, molecular testing prior to prescription is critical and essential in the era of precision medicine, which has already come to dominate our practice of lung cancer treatment.
The molecular testing for targeted therapy has been successfully applied to the tumor tissue for years, including biopsy and cytology specimens. The progress in analytic genomics facilitated by next generation sequencing (NGS) technology has made the development of high efficiency liquid biopsy possible for precisely predicting drug response as well as detecting drug resistance during the course of therapy.
The immunotherapy will be the rising-star state-of-the-art therapy in the coming decade of clinical oncology. While target-specific immunohistochemical staining as companion testing forms the corner stone of prediction biomarker, genomics studies to evaluate the mutation load and neoantigen profiles of tumor cells have been vigorously explored as the “surrogate” tests to further precisely predict the tumor response of immune checkpoint antagonists, such as anti-PD-1, anti-PD-L1 and anti CTLA4 antibodies. The roles of precision medicine cannot be overemphasized in the management of lung cancer, now and in the future.
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(2)   Identification of cellular prion protein as an invasiveness-associated protein in pulmonary adenocarcinomas: Supported by the National Science Council, we profiled the transcriptomes of in situ and invasive pulmonary adenocarcinoma cells by using laser capture microdissection of tumor cells combined with cDNA microarray analysis. Among the genes which were found significantly upregulated in invasive tumor cells, we have further characterized PRNP, the gene encoding the cellular prion protein (PrPc). Although the mis-folded form of prion protein (PrPSc) is implicated in neurodegenerative diseases such as Bovine Spongiform Encephalopathy (BSE) and Creutzfeld-Jakob Disease (CJD), the exact physiological function of PrPc remains an unsolved issue. We demonstrated the association between high PrPc expression and invasiveness of pulmonary adenocarcinoma both in clinical specimens and in cell line models. Immunohistochemical analysis showed that 91 out of 92 (99%) invasive adenocarcinoma tissues while only 1 out of 13 (8%) in situ adenocarcinoma tissues stained positive for PrPc. Semi-quantitative RT-PCR analysis in a series of human lung adenocarcinoma cell lines with variable invasive capability revealed that PrPc was expressed at low levels in less invasive cell lines while at high levels in highly invasive cell lines. Silencing of PRNP expression was performed in the highly invasive lung adenocarcinoma cell line CL1-5 by transfection of plasmids expressing shRNAs. We found that PRNP-knocked down (PRNPi) cells exhibited decreased invasion and migration, as demonstrated in matrigel invasion, transwell migration, and in vitro wound healing assays. Moreover, experimental metastasis assay showed that PRNPi cells were attenuated in the ability to form metastatic nodules in the mouse lung. In addition, PRNPi cells displayed decreased numbers of lamellipodia and diminished Rac1 activity compared to the control cells. Re-expressing of PRNP in PRNPi cells alleviated all the observed effects of silencing. Together, our results established a role of PrPc in modulating the invasion and migration of human lung adenocarcinoma cells.
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(3)   Intracellular O-GlcNAcylation Modulates the Expression of OGT and OGA: The Protein O-GlcNAcylation, as O-Phosphorylation, is an abundant, dynamic and inducible post-translational modification (PTM). This glycosylation is catalyzed by an O-GlcNAc transferase (OGT) enzyme, which transfers N-acetylglucosamine moiety from UDP-GlcNAc to serine or threonine residues of target proteins. Another enzyme, O-GlcNAcase (OGA), removes O-GlcNAc from proteins. Many reports indicated that O-GlcNAcylation can regulate gene expression, protein activity, signal transduction and is involved in the pathogenesis of many chronic diseases, including diabetes, neurodegeneration and cancer. However, the molecular mechanism underlying the regulation of O-GlcNAcylation is still not fully understood. Consistent with the results from studies by others, our data showed that elevation of cellular O-GlcNAcylation levels leads to decreased OGT and increased OGA expression in several cancer cell lines demonstrated by pharmacological and genetic approaches. On the other hand, when the cellular O-GlcNAcylation levels decrease, the OGT is up-regulated and the OGA is down-regulated. We expect that information derived from this study will provide additional insights into the molecular mechanisms through which cancer cells regulate intracellular O-GlcNAcylation levels to maintain cellular homeostasis.
 
 
 
  
Selected Publications in 2015-2019: (* Corresponding Author)

1. Lin SC, Lin CH, Shih NC, Liu HL, Wang WC, Lin KY, Liu ZY, Tseng YJ, Chang HK, Lin YC, Yeh YC, Minato H, Fujii T, Wu YC, Chen MY, Chou TY.* Cellular prion protein transcriptionally regulated by NFIL3 enhances lung cancer cell lamellipodium formation and migration through JNK signaling. Oncogene (2019) [Epub ahead of print] (SCI) (Impact factor:6.634;Rank: 6/304,1.97%)

2. Ho HL, Kao HL, Yeh YC, Chou TY*. The importance of  EGFR mutation testing in squamous cell carcinoma or non-small cell carcinoma favor squamous cell carcinoma diagnosed from small lung biopsies. Diagnostic Pathology (2019) 14(1):59 (SCI)( Impact factor:2.528;Rank: 28/76,36.84 %)

3. Ho HL, Huang CC, Ku WH, Ho CL, Lin CH, Yu SL, Chou TY.* Liquid Biopsy for Detection of EGFR T790M Mutation in Non-small Cell Lung Cancer: An Experience of Proficiency Testing in Taiwan. Journal of the Chinese Medical Association (2019) 82(6):473-476(SCI) (Impact factor:1.660;Rank: 72/155,46.45 %)

4. Chang WC, Yeh YC, Ho HL, Hsieh SL, Chou TY.* Decoy Receptor 3 Expression Is Associated With Wild-Type EGFR Status, Poor Differentiation of Tumor, and Unfavorable Patient Outcome. American Journal Of Clinical Pathology.(2019 ) 152(2):207-216 (SCI) (Impact factor:2.413;Rank: 31/79,39.24 %)

5. Yeh YC, Kao HL, Lee KL, Wu MH, Ho HL, Chou TY*. Epstein-Barr Virus-associated Pulmonary Carcinoma: Proposing an Alternative Term and Expanding the Histologic Spectrum of Lymphoepithelioma-like Carcinoma of the Lung. American Journal of Surgical Pathology (2018) 43(2):211-219. (SCI) (Impact factor: 5.878;Rank: 7/200,3.50 %)

6. Lin YC, Lin CH, Yeh YC, Ho HL, Wu YC, Chen MY*, Chou TY*. High O-linked N-acetylglucosamine transferase expression predicts poor survival in patients with early stage lung adenocarcinoma. Oncotarget. (2018) 9(57)31032-31044(SCI)(Impact factor: 5.168;Rank: 44/217, 20.28%)

7. Xu ES, Yang MH, Huang SC, Liu CY, Yang TT, Chou TY,* Hwang TZ, Hsu CT. ECE-1 overexpression in head and neck cancer is associated with poor tumor differentiation and patient outcome. Oral Diseases(2018)Epub ahead of print(SCI)(Impact factor: 2.310;Rank: 21/91, 23.08%)

8. Lin YY, Hsu WH, Wu MH, Chou TY*. Pleuroparenchymal fibroelastosis presenting with pneumothorax. SAGE Open Medical Case Reports (2018) 6:1-4

9. Xu ES, Yang MH, Liu CY, Liu KW, Yang TT, Chou TY*, Hwang TZ,* Hsu CT.* Decreasing cytokeratin 17 expression in head and neck cancer predicts nodal metastasis and poor prognosis: the first evidence. Clinical Otolaryngology (2018)Epub ahead of print(SCI)(Impact factor: 2.523;Rank: 7/41, 17.07%)

10. Tseng YH, Ho HL, Lai CR, Luo YH, Tseng YC, Whang-Peng J, Lin YH, Chou TY*, Chen YM.* Brief Report: PD-L1 expression of tumor cells, macrophages, and immune cells in non-small cell lung cancer patients with malignant pleural effusion. Journal of Thoracic Oncology (2018) 13(3):447-453 (SCI)(Impact factor:10.340;Rank: 6/59, 10.17%)

11. Wu YC,* Wei NC,* Hung JJ, Yeh YC, Su LJ, Hsu WH, Chou TY*. Generating a robust prediction model for stage I lung adenocarcinoma recurrence after surgical resection. Oncotarget (2017) 8(45):79712-79721 (SCI)(Impact factor: 5.168;Rank: 44/217, 20.28%)

12. Hung JJ,* Yeh YC, Wu YC, Chou TY,* Hsu WH.* Prognostic Factors in Completely Resected Node-negative Lung Adenocarcinoma of 3cm or Smaller. Journal of Thoracic Oncology (2017) 12(12):1824-1833 (SCI)(Impact factor: 6.595;Rank: 6/59, 10.17%)

13. Kao HL, Yeh YC, Lin CH, Hsu WF, Hsieh WY, Ho HL,* Chou TY.* Diagnostic algorithm for detection of targetable driver mutations in lung adenocarcinomas: Comprehensive analyses of 205 cases with immunohistochemistry, real-time PCR and fluorescence in situ hybridization methods. Lung Cancer (2016) 101:40-47 (SCI)(Impact factor: 4.294;Rank: 11/59, 18.64%)

14. Luo YH, Ho HL, Tsai CM, Shih JF, Chiu CH, Lai SL, Lee YC, Perng RP, Whang-Peng J, Chou TY,* Chen YM.* The Association Between Tumor Epidermal Growth Factor Receptor (EGFR) Mutation and Multiple Primary Malignancies in Patients With Adenocarcinoma of the Lungs. American Journal of Clinical Oncology-Cancer Clinical Trials (2015) 38(2):147-151(SCI)(Impact factor: 3.259;Rank: 96/217, 44.24%)

15. Chiu CH, Ho HL, Doong H, Yeh YC, Chen MY, Chou TY,* Tsai CM.* MLH1 V384D polymorphism associates with poor response to EGFR tyrosine kinase inhibitors in patients with EGFR L858R-positive lung adenocarcinoma. Oncotarget (2015) 6(10):8407-8417

 

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