Lung – National Health Research Institutes (Coordinating Center)

Brief Description of Project:

Lung cancer is the leading cause of cancer mortality in Taiwan. The genetic epidemiology and pharmacogenomic studies have revealed that lung cancer in Taiwan and East Asia, especially lung adenocarcinoma for females and non-smokers, is a distinct disease and different from the patients seen in western countries. The Consortium for "Early Detection of Lung Cancer by Genomic and Proteomic Approaches" is a nation-wide, multi-institutional research project aimed to identify biomarkers for early identification of lung cancer via blood test and to develop useful prognostic and predictive biomarkers for possible clinical applications. By getting together scientists with different expertise in the fields of genomics, proteomics, bioinformatics and genetic epidemiology, this Consortium attempts to discover the genomic and proteomic markers for early detection of lung cancer using common specimens and state-of-the-art technologies. The candidate biomarkers will be further verified by prospective clinical trial using the Lung Cancer network established by this team. This team has already collected more than 2500 lung cancer patients' DNAs and serum samples as well as the controls. By use of the genomic approach using microarray technology, this team has also identified several candidate genes and microRNA as molecular signatures useful for prognostic prediction.

Team Members and Expertise:

Cheng-Wen Wu, MD, PhD
Dr. Wu is an active leader in the Chinese biomedical community. Dr. Wu initiated numerous clinical training programs, formed the first working group for multi-centered clinical trials, conducted timely research on important and urgent health issues, established a peer-review system and spurred international collaborations not only with excellent results but also achieved national and international impact. He is also the program director of the Lung Cancer National Research Program for Genomic Medicine in Taiwan. Dr. Wu has made many clinically significant contributions to the studies of human cytomegalovirus infection and the genomic applications of cancer metastasis in lung adenocarcinoma, two of the most serious health threats to the Chinese population. Dr. Wu's laboratory aims to understand the roles of adhesion molecules and receptor tyrosine kinases in lung cancer invasion and metastasis. By establishing a "tumor-cell invasion core unit" equipped with several series of low- and high-metastatic cell models, they provide high quality services and perform technical training for different laboratories of the institutes. Dr. Wu is best known for his work on the molecular mechanism of gene transcription. He presented the earliest biophysical evidence of the 4-step mechanism of RNA polymerase reaction, discovered the presence of intrinsic zinc in transcription, and demonstrated the regulation of the sigma cycle by nanosecond fluorescence spectroscopy, all important breakthroughs in the field of molecular biology.

Pan-Chyr Yang, MD, PhD
Dr. Yang is currently the Dean and Professor of Medicine, National Taiwan University College of Medicine. He is also the President of Taiwan Society of Pulmonary and Critical Care Medicine. His major research interests are pulmonary and critical care medicine, lung cancer genomics and molecular biology, as well as microarray gene expression technology. Dr. Yang is the director of the microarray core facility of the National Research Program Gram Project. His group has identified several novel lung cancer tumor suppressor genes and biomarkers that may have potential for clinical application in the personalized therapy of lung cancer.

Chien-Jen Chen, ScD
Dr. Chen is a member of Academia Sinica and a world-wide renown expert in molecular and genomic epidemiology. Research in the Chen lab encompasses a broad spectrum of molecular and genomic epidemiology. This research includes 1) a long-term follow-up study on the predictability of risk of hepatocellular carcinoma, cervical carcinoma and nasopharyngeal carcinoma for various biomarkers of chronic infection of hepatitis B and C virus, human papillomavirus and Epstein-Barr virus, respectively; 2) molecular biomarkers of chronic arsenic poisoning: gene-environment interaction; 3) a multiplex family study and association study on susceptibility genes of cancers of hepatocellular carcinoma, cervical carcinoma and nasopharyngeal carcinoma; and 4) a genomic epidemiological study on susceptibility genes of female lung adenocarcinoma.

Yi-Ching Wang, PhD
Dr. Wang is currently a Professor in the Department of Pharmacology, College of Medicine, National Cheng Kung University. She studies the molecular mechanisms involved in lung tumorigenesis in Taiwan. Lung cancer is the leading cause of cancer deaths among women and men in Taiwan. Evidence shows that there are many unique genetic and epigenetic alterations in Taiwanese lung cancer compared to that in other countries. Therefore, Dr. Wang investigates the etiological association of alterations in several tumor suppressor genes, oncogenes, and DNA repair genes with lung tumorigenesis in Taiwan. The alteration analyses include the following aspects: gene mutation and polymorphism, gene loss, hypermethylation of promoter, chromatin structure alteration of gene locus, mRNA alteration, and altered protein expression. More recently, Dr. Wang has continued to do research on cancer genomics such as (1) genome-wide search of loss of heterozygosity of microdissected primary lung tumors, (2) comparison of mRNA expression profiles between chemo-resistant and -sensitive lung cancer patients, and (3) genome-scanning approaches of DNA methylation and chromatin alteration profiles for identification of new genes critical to lung tumorigenesis. In addition, several potential anti-cancer drugs are developing in her laboratory. Dr. Wang has established connections to physicians at different hospitals for collecting tumor, blood, and paraffin-embedded tissue samples of lung cancers and their appropriate controls.

Chao Agnes Hsiung, PhD
Dr. Hsiung is Director of the Division of Biostatistics and Bioinformatics, National Health Research Institutes, Taiwan. She received her PhD from Columbia University. Her research interests include genetic epidemiological studies and array-based functional genomic studies. Dr. Hsiung has been program PI for the multi-center genetic epidemiological study on lung adenocarcinoma funded by the Department of Health in Taiwan. She is also a Co-PI of a National Science Council funded Bioinformatics Core Facilities.

Chang Gee-Chen, MD, PhD
Dr. Gee-Chen is board-certified and fully licensed in Internal Medicine, board-eligible in Adult Oncology, and has more than ten years of clinical experience diagnosing and treating lung cancer. While a graduate student in molecular toxicology, he trained in the laboratory of Dr. Hsu Gow-Ton studying checkpoint regulation of cell cycle progression and apoptosis in lung cancer cell lines in response to a targeted therapeutic agent, gefitinib. As an oncology physician at Taichung Veterans General Hospital, he gained considerable clinical experience designing and generating large clinical and microarray datasets geared at finding biomarkers of cancer recurrence and response to treatment.

Wun-Shaing Wayne Chang, PhD
Dr. Chang is an Assistant Principal Investigator at the Institute of Cancer Research, National Health Research Institutes, Taiwan. Dr. Chang received his PhD in Biomedical Sciences from the Department of Hematology, University of Cambridge, U.K. Dr. Chang is a member of the International Proteolysis Society. His research interests focus on the identification and characterization of metastasis-related proteolytic enzymes, in particular the tissue kallikrein family and its Janus-faced role in regulating the invasive behavior of lung tumor cells. Dr. Chang also aims to investigate the interactions between secreted kallikrein molecules and the tumor microenvironment, and their potential use as biomarkers for diagnosis, prognosis and as targets of therapy for lung cancer.

Chih-Yi Chen, MD
Dr. Chen is a Vice Superintendent of Cancer Center of China Medical University Hospital and a Professor of thoracic surgery in the China Medical University. Dr. Chen is an experienced surgeon and has expertise in lung cancer clinical research. He is President of Taiwan Lung Cancer Society, and Taiwan Governor of American College of Chest Physicians (ACCP). He previously was a Chief of Thoracic Surgery, Taichung Veterans General Hospital. His surgical team provides the surgically resected normal lung and tumor lung samples from lung cancer patients as well as blood samples from lung cancer patients and non-cancer subjects. These samples are collected from patients admitted to Veterans General Hospital-Taichung between 1993 and 2004, and will be continuously collected at Chinese Medicine University Hospital during this study. All samples contain full clinicopathological records with systematically files in computer. In addition, Dr. Chen and his teams of clinicians will perform follow-up for all subjects. Dr. Chen also made a broad investigation in the surgical management of patients with myasthenia gravis (MG), including preoperative preparation for MG patients and the factors influencing the outcome of MG patients after transsternal thymectomy. He found that thymoma is associated with relapse of symptoms after thymectomy.

Konan Peck, PhD
Dr. Peck is a research fellow in the Institute of Biomedical Sciences, Academia Sinica. He specializes in the areas of DNA microarray, gene chip technology, molecular diagnostics and analytical molecular biology. His lab has developed circulating cancer cell detection technology, established a viral chip platform for identification of unknown pathogens, and his group has also identified several biomarkers that are potentially useful for cancer detection. Recent research interests are developing aptamer technology for diagnostic and targeting agents for various cancers.