Dr. Yi-Rong Chen

YR Chen

Yi-Rong Chen, Ph.D.

Associate Investigator
Institute of Molecular and Genomic Medicine
yrchen@nhri.edu.tw

EDUCATION

Ph.D., Institute of Microbiology and Immunology, Baylor College of Medicine (1998), Lab of Dr. Tse-Hua Tan; Apoptotic signaling mediated by c-Jun N-terminal kinase
M.S., Institute of Microbiology and Immunology, National Yang-Ming Medical College (1991), Lab. of Dr. Sheng-Yuan Wang; purification and characterization of a bone marrow-derived hematopoietic colony-promoting activity
B.S., Department of Medical Technology, National Taiwan University (1989)

PROFESSIONAL EXPERIENCES

1988-1989       Training Student, Institute of Biomedical Science, Academia Sinica, Taiwan, ROC
1990-1991       Research Assistant, Veterans General Hospital, Taipei, Taiwan, ROC
1993-1994       Research Assistant, Institute of Biomedical Science, Academia Sinica, Taiwan
1998-2002       Postdoctoral Associate, Baylor College of Medicine, Houston, Texas
2002-2003       Assistant Professor, Department of Immunology, Baylor College of Medicine, Houston, Texas
2003-2008       Assistant Investigator, Division of Molecular and Genomic Medicine, National Health Research Institutes, Taiwan, ROC
2008-present       Associate Investigator, Institute of Molecular and Genomic Medicine, National Health Research Institutes, Taiwan, ROC

RESEARCH INTERESTS

EGFR mutations and lung adenocarcinoma (LAC)

EGFR mutations are closely associated with LAC in East Asian populations. We find that different EGFR mutants become constitutively phosphorylated through distinct mechanisms. Our recent findings show that EGFR are refractory to negative feedback modifications in LAC cells with EGFR mutation. Additionally, we have established transgenic animal models for EGFR mutant-triggered LAC.

Functions of atypical dual specificity phosphatases (DUSPs)

Through gene expression profiling, we found that the expression levels of several atypical DUSP are decreased in lung cancer tissues in comparison to normal lung tissues. We found that these atypical DUSPs are involved in the negative regulation of protein tyrosine kinases, such as EGFR and FAK, which play important roles in oncogenesis. Knockout animal models are currently under examinations for the biological functions of those DUSPs in vivo.

Development of novel cancer therapeutic agents

Through a cell-based high throughput screening methods, we have identified several compounds that can suppress EGFR-supported cell growth. Based on the lead compounds, we have developed a group of EGFR kinase inhibitors which showed inhibitory efficacy similar to the EGFR inhibitor in clinical use.

HONORS & AWARDS

1986-1989       Book Coupon Awards (National Taiwan University, Taiwan)
1990-1991       Outstanding Student Scholarship (National Yang-Ming Medical College, Taiwan)
1995       Travel Award (Keystone Symposium; provided by NIH)
1996       Platform Presentation Award (Graduate Student Symposium, Baylor College of  Medicine, Houston)
1997-1998       Dean’s Award (Graduate School, Baylor College of Medicine)
1997-1999       Predoctoral Fellowship (Breast Cancer Research Program, Department of Defense, USA)
1997       Alexander Wang Memorial Scholarship (SCBA-Texas Chapter Symposium, 1998)
1999-2002       Postdoctoral Fellowship (Prostate Cancer Research Program, Department of Defense, USA)
2000       Travel Award (Keystone Symposium; NIH Grant #1 R13 CA85280-01)
2013        The 10th National Innovation Award (Pre-clinical and clinical development of DBPR112, a novel EGFR tyrosine kinase inhibitor as a therapeutic candidate for lung adenocarcinoma)

SELECTED PUBLICATIONS

  1. Chen YR, Fu YN, Lin CH, Yang ST, Hu SF, Chen YT, Tsai SF, Huang SF. Distinctive activation patterns in constitutively active and gefitinib-sensitive EGFR mutants. Oncogene, 25: 1205-1215, 2006
  2. Wang JY, Lin CH, Yang CH, Tan TH, Chen YR. Biochemical and biological characterizations of a neuroendocrine-associated phosphatase (NEAP). J. Neurochem. 98: 89-101, 2006
  3. Fu YN, Yeh CL, Cheng HH, Yang CH, Tsai SF, Huang SF, Chen YR. EGFR mutants found in non-small cell lung cancer show different levels of sensitivity to suppression of Src: implications in targeting therapy. Oncogene, 27: 957-965, 2008
  4. Lin WH, Song JS, Chang TY, Chang CY, Fu YN, Yeh CL, Wu SH, Huang YW, Fang MY, Lien TW, Hsieh HP, Chao YS, Huang SF, Tsai SF, Wang LM, Hsu JT, Chen YR. A cell-based high-throughput screen for epidermal growth factor receptor pathway inhibitors. Anal. Biochem., 377: 89-94, 2008
  5. Wang JY, Yang CH, Yeh CL, Lin CH, Chen YR. Neuroendocrine-associated phosphatase (NEAP) causes down-regulation of epidermal growth factor receptor, subsequently induces the suppression of nerve growth factor-induced differentiation in PC12 cells. J. Neurochem. 107: 1544-1555, 2008
  6. Li JP, Fu YN, Chen YR*, and Tan TH*. JNK pathway-associated phosphatase dephosphorylates focal adhesion kinase and suppresses cell migration. J. Biol. Chem. 285: 5472-5478, 2010 (*corresponding authors)
  7. Wang JY, Yeh CL, Chou HC, Yang CH, Fu YN, Chen YT, Cheng HW, Huang CY, Liu HP, Huang SF, Chen YR. Vaccinia H1-related phosphatase (VHR) is a phosphatase of ErbB receptors and is down-regulated in non-small cell lung cancer. J Biol. Chem. 286:10177-10184, 2011
  8. Yang CH, Chou HC, Fu YN, Yeh CL, Cheng HW, Chang IC, Liu KJ, Chang GC, Tsai TF, Tsai SF, Liu HP, Wu YC, Chen YT, Huang SF*, Chen YR*. EGFR over-expression in non-small cell lung cancers harboring EGFR mutations is associated with marked down-regulation of CD82. BBA-Mol. Basis Dis., 1852: 1540–1549, 2015(*corresponding authors)
  9. Yang CH, Yeh YJ, Wang JY, Liu YW, Chen YL, Cheng HW, Cheng CM, Chuang YJ, Yuh CH, Chen YR. NEAP/DUSP26 suppresses receptor tyrosine kinases and regulates neuronal development in zebrafish. Sci. Reports,7: Article number 5241, 2017
  10. Chen YR*, Chou HC, Yang CH, Chen HY, Liu YW, Lin TY, Yeh CL, Chao WT, Tsou HH, Chuang HC, Tan TH*. Deficiency in VHR/DUSP3, a suppressor of focal adhesion kinase, reveals its role in regulating cell adhesion and migration. Oncogene, 36:6509-6517, 2017 (*corresponding authors)

PATENT

1.專利名稱:作為酪胺酸激酶抑制劑之稠合雙環及多環嘧啶化合物
申請人: 謝興邦; Coumar, Selvaraj Mohane; 趙宇生; 徐祖安; 林文星; 陳怡榮
申請日期: 2009.11.9; 核准日期: 2012.12.13;
獲證日期: 2013.02.11; 證書號數: I385174;
專利申請國: 中華民國
專利公開號: 201018696

2. Patent Title: Fused Bicyclic And Tricyclic Pyrimidine Compounds as Tyrosine Kinase Inhibitors Applicants: Hsieh, Hsing-Pang; Coumar, Selvaraj Mohane; Hsu, Tsu-An; Lin, Wen-Hsing; Chen, Yi-Rong; Chao, Yu-Sheng
Application Date: 2008.11.10; Nation: USA; Application Number: 12/614584
Patent number: US8507502B2; Patent date: Aug. 13, 2013
Agent: Occhiuti Rohlicek & Tsao LLP, Cambridge, MA, USA

3. Patent Title: 作为酪胺酸激酶抑制剂的稠合双环及多环嘧啶化合物
Applicants: Hsieh, HP;Coumar, MS;Hsu, TA;Lin, WH;Chen, YR;Chao, YS
Nation: PRC; Patent number: CN102264745B; Patent date: July 22, 2015

4. Patent Title: Fused Bicyclic And Tricyclic Pyrimidine Compounds as Tyrosine Kinase Inhibitors
Applicants: Hsieh, Hsing-Pang; Coumar, Selvaraj Mohane; Hsu, Tsu-An; Lin, Wen-Hsing; Chen, Yi-Rong; Chao, Yu-Sheng
Application Date: 2009.11.9; Nation: Patent Cooperation Treaty;
Application Number: PCT/US2009/063684
Agent: Occhiuti Rohlicek & Tsao LLP, Cambridge, MA, USA

Lab Members

121113_276180

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