研究(Research)

我們實驗室之研究方向為開發偵測及定量物生物分子(包括蛋白質及代謝物)之質譜技術，這些方法已經被用來研究細胞模式及臨床組織及體液等真實樣品，並經由國際合作保持技術的新穎性。我們的研究目標在於利用本實驗室之專長(蛋白質體、代謝體及生物質譜技術)了解泌尿系統癌症之生物機制，利用體學的方法研究膀胱癌及腎臟癌細胞株、腫瘤組織及尿液，希望找尋早期診斷癌症之非侵入式生物標記。

並與泌尿科、腎臟科、婦產科、小兒科等臨床醫生合作，運用蛋白質體及代謝體等後基因體學研究方法，全面性的研究正常與疾病生物系統(細胞株及臨床收集的體液或組織)中蛋白質與代謝物之群體變化，監測各個分子在疾病所扮演的角色，探討惡性與良性泌尿系統疾病發生及惡化之生物機制，以期朝向臨床應用及個人化醫療邁進。

The major topics of our research group are to develop methods and strategies, primarily based on mass spectrometry (MS), for the detection and quantification of biological molecules, including peptides, proteins, and metabolites. There approaches have been applied to study real-world biological systems including cells, tissues, and body fluids. Our research goals are focused on understanding the basis of molecular oncology of urological system by applying our specialties, including proteomics, metabolomics, biological mass spectrometry, and analytical biochemistry, through independent research ability and international collaboration.

Interest in exploring human proteome has broadened the search for new biomarkers, as well as disease etiology studies. Biomarker discovery in body fluid recently has gained prominence, and numerous investigations have found that levels of specific proteins increase or decrease during disease. One of the main challenges in biomarker discovery is high biological variation between individuals. Therefore, after the discovery phase, potential biomarkers must be verified in a large number of samples. Accurate quantitation of proteins in each sample is part of this verification phase. However, absolute quantitation of numerous proteins in body fluids has not been systematically performed, and their roles as useful “biosignatures” are unknown. This study thus focuses on developing the SISCAP (stable isotope standards and capture by anti-peptide antibodies, namely immuno-MRM-MS) platform to quantitate proteins and peptides in biological specimens. Our lab is responsible for setting up the MRM-MS assay for biomarker verification in a large number of clinical specimens. Using data generated from various techniques of the individual patient combined with large scale modeling of the network of cancer relevant pathways in the individual tumor, a relevant prediction can be deduced towards an individualized therapy for cancer.

目前實驗室的研究方向如下 :

1. 以系統性方法找尋及驗證泌尿系統癌症之生物標誌及其生物重要性

(Using a Systems Approach to Discover and Assess Urological Cancer Biomarkers)

我們研究了膀胱癌細胞株之分泌蛋白質體以及臨床醫生取得之腫瘤及尿液組成蛋白體，經由交叉比對，已經發現一系列可能隨著癌症的發生而產生表現量改變的分子，未來將持續驗證其重要性，並研究其與病理狀況之相關性，了解其在泌尿系統研症所扮演之角色。並延伸到多種泌尿系統良性疾病的機制研究，例如腎衰竭、腹膜炎等。

2. 發展標靶性及多重定量特性之MRM-MS技術在大量臨床樣品中驗證疾病生物標誌之重要性

(Targeted and Multiplexed Quantitation of Proteins for Verification of Biomarker Panels using Multiple-Reaction-Monitoring MS (MRM-MS) and immune MRM-MS. Collaboration with Prof. Christoph Borchers, the Director of the University of Victoria Genome BC Proteomics Centre, Canada; and clinical teams in Chang Gang Memorial Hospital)

蛋白質體學是當今疾病生物標誌研究中最熱門的研究領域之一。我們研究團隊過去的研究成功地以iTRAQ技術分析發現膀胱癌病患尿液檢體中多種蛋白質生物標誌，同時也已建立「液相層析多重反應監測質譜定量分析技術」(LC-MRM-MS)，首度完成於人類臨床尿液樣本中同步定量63個蛋白質分子的研究工作，此技術將可協助研究學者在大量檢體中驗證過去所找到的生物標記後選分子，未來將繼續發展「免疫濃縮-液相層析多重反應監測質譜定量分析技術」(immuno-MRM-MS)及生物資訊分析方法，以擴展至其他疾病或不同型態的檢體。

Development of MRM-MS assays for protein biomarker verification

3. 利用標靶定量技術同時分析生物路徑中之多種蛋白質及代謝物分子，以系統生物學的方法闡明疾病發生及進展過程中所參與的生物反應機制

(Development and Applications of Targeted Proteomic and Metabolomic Approaches in Cancer Biology to study Urological Oncology. Collaboration with Prof. Liang Li, Department of Chemistry, University of Alberta, Canada)

隨著標靶定量技術的發展，我們開始可以利用質譜方法大規格的追蹤參與特定生物反應機制之多種蛋白質及代謝分子，比較細胞模式在不同處理條件下的表現量，監測各個分子在疾病所扮演的角色，並在個人臨床樣品中驗證，以期朝向個人化醫療邁進。