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周德盈 Chou, Teh-Ying
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、

Tel: 02-28757080
2016 (expected)
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)
National Yang-Ming University, Taiwan.
Academic appointments
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
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
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
Academic Prize for Excellent Research, Taipei Veterans General Hospital
Best Clinical Teacher Award, Taipei Veterans General Hospital
Outstanding Physician, Veterans Affairs Commission, Executive Yuan, Taiwan
National Science Council Scholar, Taiwan
        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.
(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.
(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 2010-2015: (* Corresponding Author)
1.       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
2.       Hung JJ,* Yeh YC, Jeng WJ, Wu KJ, Huang BS, Wu YC,* Chou TY,* Hsu WH.* Predictive Value of the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Classification of Lung Adenocarcinoma in Tumor Recurrence and Patient Survival. Journal of Clinical Oncology (2014) 32(22)2357-2364
3.       Lin YC, Chen YN, Lin KF, Wang FF, Chou TY,* Chen MY.* Association of p21 with NF-YA suppresses the expression of Polo-like kinase 1 and prevents mitotic death in response to DNA damage. Cell Death & Disease (2014) 5:e987
4.       Chiu CH, Ho HL, Chiang CL, Lin SF, Ma HH, Chuang YT, Lin KY, Tsai CM, Chou TY.* Clinical Characteristics and Treatment Outcomes of Lung Adenocarcinomas with Discrepant EGFR Mutation Testing Results Derived from PCR-Direct Sequencing and Real-Time PCR-Based Assays. Journal of Thoracic Oncology (2014) 9(1):91-96 
5.       Yeh YC, Chou TY.* Pulmonary neuroendocrine tumors: Study of 90 cases focusing on clinicopathological characteristics, immunophenotype, preoperative biopsy, and frozen section diagnoses. Journal of Surgical Oncology (2014) 109(3)280-286
6.       Hsu PK, Kao HL, Chen HY, Yen CC, Wu YC, Hsu WH, Chou TY.* Loss of CRNN expression is associated with advanced tumor stage and poor survival in patients with esophageal squamous cell carcinoma. Journal of Thoracic and Cardiovascular Surgery (2014) 147(5)1612-1618
7.       Ho HL*, Chang FP, Ma HH, Liao LR, Chuang YT, Chang-Chien YC, Lin KY, Chou TY*. Molecular diagnostic algorithm for epidermal growth factor receptor mutation detection in Asian lung adenocarcinomas: Comprehensive analyses of 445 Taiwanese cases with immunohistochemistry, PCR-direct sequencing and Scorpion/ARMS methods. Respirology (2013) 18(8):1261-1270
8.       Yeh YC, Wu YC, Chen CY, Wang LS, Hsu WH, Chou TY.* Stromal invasion and micropapillary pattern in 212 consecutive surgically resected stage I lung adenocarcinomas: histopathological categories for prognosis prediction. Journal of Clinical Pathology (2012) 65(10):910-918
9.       Hsiao BY, Chen CC, Hsieh PC, Chang TK, Yeh YC, Wu YC, Hsu HS, Wang FF, * Chou TY.* Rad is a p53 direct transcriptional target that inhibits cell migration and is frequently silenced in lung carcinoma cells. Journal of Molecular Medicine-JMM (2011) 89(5):481-492
10. Hung JJ, Jeng WJ, Hsu WH, Lin SF, Hsieh CC, Huang BS, Huang MH, Liu JS, Chou TY, * Wu YC. * Prognostic factors in pathological stage IB non-small cell lung cancer greater than 3 cm. European Respiratory Journal (2010) 36(6):1355-1361
11. Yeh YC, Chou TY. * Pulmonary adenocarcinoma with microcystic histology and intratumoral heterogeneity of EGFR gene polymorphism. Histopathology (2010) 57(1):112-120
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