陳璿宇

Hsuan-Yu Chen

 

Institute of Statistical Science, Academia Sinica
 

Tel: 886-2-27835611 ext 415

        886-2-23123456 ext 88698

Fax: 886-2-27835611 ext 475
E-mail: hychen@stat.sinica.edu.tw

 


學歷
2003年9月- 2007年1月 博士 流行病學研究所 台灣大學
現職
2008年5月迄今 助研究員 統計科學研究所 中央研究院
經歷
2007年1月- 2008年5月 博士後研究 統計科學研究所 中央研究院

研究興趣

  1. 生物資訊
  2. 生物統計與流行病學
  3. 整合性癌症生物學
  4. 個人化醫療

獎勵與榮譽

  1. 97年國科會優秀技轉貢獻獎
  2. 第17屆王民寧先生紀念紀金會優秀博士論文獎, 2007

研究方向

  1. 整合性癌症生物學

整合性癌症生物學是癌症研究的新潮流,它的特點是在融合許多片段的生物醫學發現,從分子到臨床層次,以系統研究方式,增進對癌症的了解。而這個整合的動力必須來自於數學模型(mathematical modeling)和計算(computation)方面的新發展。本計畫鎖定台灣女性肺癌的癌症轉移機制為研究重點。首先利用比較性基因體雜合技術探討DNA變異的情形 。在RNA轉錄層次的研究中,利用高密度寡核甘酸晶片測量近4萬個基因的表現。蛋白質轉譯層次的上,測量目前新發現的微小核醣核酸(microRNA)在臨床檢體中的變化,以此推估後續蛋白質合成的狀態。上述三種層次的研究 所產生相當龐大的資料, 必須結合生物資訊以及系統生物學的方法,才能合併考量生物體三種層次的變異,尋找出台灣女性肺腺癌的分子機制。 除了引用文獻上多種統計方法外,更將充分運用liquid association, generalized association plot, Context-dependent clustering 等新進資料分析工具進行探討。癌症轉移研究成果可應用於尋求抑制轉移的臨床醫療策略 並作為其它癌症研究的借鏡 。

  1. 以全基因體組掃描和再定序策略找尋新穎的肺癌診斷與預後印記

The processes of malignant transformation from normal cell to cancer cell are complex. These phenomena can be described in three major levels: genomic DNA, DNA transcribes to RNA, and RNA translates to protein. Recent studies demonstrated the potential applications of these genomic biomarkers by identification of specific changes at the above three molecular levels. However, the molecular changes measured in cancer tissues can not directly translate to the somatic susceptibility in lung cancer patients. Genotyping chips were performed in comparisons of population difference and genomic variation between diseases and related controls. The utilities of such genome-wide association studies provide the potential clue of disease causation and benefits of preventive medicine. In this study, a nested case-control study is designed to explore the genome-wide association of lung cancer by using SNP genotyping arrays. The genomic variations of incident lung cancer cases and matched controls form study population (23,943 participants) will be assayed by more than 900K SNP and copy number variation probes and can make the scanning resolution less than 700 base pair. The findings of this study may have a chance to resolve the problems of the somatic susceptibility and benefit the preventive medicine in lung cancer.

 

過去研究成果
本研究團隊2007年於新英格蘭醫學期刊 (New England Journal of Medicine)發表一個五個基因為基礎的肺癌預後預測印記,可準確地預測癌症復發和肺癌患者的存活率。進一步利用現代生物技術與生物統計演算法,發現一個以五個微核醣核酸(microRNA)為基礎的預測肺癌復發率及存活率的癌症印記,對於未來癌症的個人化醫療的發展,提供了重要的資訊,這一研究成果已發表於本期癌症醫學領域的頂尖期刊-癌細胞(Cancer Cell),該成果目前正在申請世界性專利。
此外,我們進一步結合於新英格蘭醫學期刊(New England Journal of Medicine)發表的五個基因與五個微核醣核酸兩種不同分子調控層次的基因印記,結果發現當病人同時被兩種印記判定為高風險病人時,其有著顯著地較高的癌症復發與死亡風險。為進一步測試這兩種肺癌預後預測印記的準確性,一項涵蓋台大醫院、台中榮民總醫院與中國醫藥大學附設醫院在內,且由衛生署支持的多醫學中心大規模臨床試驗正在進行中。
本團隊初步證明利用肺癌預後預測印記可以準確地預測癌症復發和肺癌患者的存活率。此項發現可應用於癌症分子病理學的研究或新標靶性治療的開發,更可進一步發展成癌症檢測試劑,以用於評估病患預後,並可有助於選擇高風險的癌症病人,在早期即進行輔佐性化療,或給予更進一步的治療。
本團隊除了在臨床與基礎生物學上的研究外,對於生物訊學與系統生物學方面的研究,已進行初步發展。利用拓譜學 (topology)為基礎的癌症分類演算法,在區分不同型態的癌症有相當高的準確率。我們已建構了生物資訊線上分析網站 (CRSD),提供微陣列晶片線上分析系統,以及其他基礎研究的相關資料庫工具,能提供研究者在資料分析與研究上的幫助。

 

期刊論文著作

  1. Sung-Liang Yu, Sher Singh, Huei-Wen Chen, Hsuan-Yu Chen, Jeremy J.W. Chen, Wen-Jone Chen, Han-Shiang Chen, Shyr-Chyr Chen. (2008) Intra-abdominal Adhesion Formation Induces Anti-oxidative Injury, Enhances Cell Proliferation, and Prevents Complement-mediated Lysis. Wound Repair and Regeneration 16; 388-98. (Impact Factor: 2.23; Rank: 25/138)
  2. Sung-Liang Yu, Hsuan-Yu Chen, Gee-Chen Chang, Chih-Yi Chen, Huei-Wen Chen, Sher Singh, Chiou-Ling Cheng, Chong-Jen Yu, Yung-Chie Lee, Han-Shiang Chen, Te-Jen Su, Ching-Cheng Chiang, Han-Ni Li, Qi-Sheng Hong, Hsin-Yuan Su, Chun-Chieh Chen, Wan-Jiun Chen, Chun-Chi Liu, Wing-Kai Chan, Wei J. Chen, Ker-Chau Li, Jeremy J.W. Chen, and Pan-Chyr Yang. (2008) MicroRNA Signature Predicts Survival and Relapse in Lung Cancer. Cancer cell 2008;1; 48-57. (Impact Factor: 24.08; Rank: 3/127)
  3. Yu, S. L., Chen, H. Y., Yang, P. C., Chen, J.J.W. Unique MicroRNA Signature and Clinical Outcome of Cancers, DNA and Cell Biology, 2007, 26, 283-292 (review article) (contributed equally to the first author) (Impact Factor: 1.905; Rank: 172/262)
  4. Chen, H. Y., Yu, S. L., Chen, C. H., Chang, G. C., Chen, C. Y., Yuan, A., Cheng, C. L., Wang, C. H., Terng, H. J., Kao, S. F., Chan, W. K., Li, H. N., Liu, C. C., Singh, S., Chen, W. J., Chen, J.J.W., and Yang, P. C. A 5-Gene Signature and Clinical Outcome in Non-small Cell Lung Cancer, N Engl J Med, 2007, 356, 11-20. (Impact Factor: 51.296; Rank: 1/103)
  5. Liu, C. C., Chen, W. S.E., Lin, C. C., Liu, H. C., Chen, H. Y., Yang, P. C., Chang, P. C., and Chen, J.J.W. Topology-based cancer classification and related pathway mining using microarray data, Nucl Acids Res, 2006, 34, 4069-4080. (Impact Factor: 6.317; Rank: 36/262)
  6. Liu, C. C., Lin, C. C., Chen, W. S.E., Chen, H. Y., Chang, P. C., Chen, J.J.W. and Yang, P. C. CRSD: a comprehensive web server for composite regulatory signature discovery, Nucl Acids Res, 2006, 34, W571-577. (Impact Factor: 6.317; Rank: 36/262)
  7. Tsai, M. F., Wang, C. C., Chang, G. C., Chen, C. Y., Chen, H. Y., Cheng, C. L., Yang, Y. P., Wu, C. Y., Shih, F. Y., Liu, C. C., Lin, H. P., Jou, Y. S., Lin, S. C., Lin, C. W., Chen, W.J., Chan, W. K., Chen, J.J.W. and Yang, P. C. A New Tumor Suppressor DnaJ-like Heat Shock Protein, HLJ1, and Survival of Patients With Non-Small-Cell Lung Carcinoma, J Natl Cancer Inst, 2006, 98, 825-838. (Impact Factor: 15.271; Rank: 4/127)
  8. Chen, J.J., Lin, Y.C., Yao, P.L., Yuan, A., Chen, H.Y., Shun, C.T., Tsai, M.F., Chen, C.H. and Yang, P.C. Tumor-associated macrophages: the double-edged sword in cancer progression, J Clin Oncol, 2005, 23, 953-964. (Impact Factor: 13.598; Rank: 5/127)
  9. Chen, W.J., Chen, H.W., Yu, S.L., Huang, C.H., Wang, T.D., Chen, J.J., Chien, C.T., Chen, H.Y., Yang, P.C. and Lee, Y.T. Gene expression profiles in hypoxic preconditioning using cDNA microarray analysis: altered expression of an angiogenic factor, carcinoembryonic antigen-related cell adhesion molecule 1, Shock, 2005, 24, 124-131. (Impact Factor: 3.318; Rank: 12/138)
  10. Chou, W.C., Chen, H.Y., Yu, S.L., Cheng, L., Yang, P.C. and Dang, C.V. Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation, Blood, 2005, 106, 304-310. (Impact Factor: 10.37; Rank: 2/61)