研究興趣:

        我的研究重點分為兩大部分,一是以分子及細胞生物學為主的醫學生物基礎研究,和另外一是以醫學生物技術及應用為主的研究與發展。

        在醫學生物基礎研究上,我的研究方向如下

  1. 是研究與巨噬細胞有關的血管疾病之致病機轉與其細胞訊息傳導。其病理上以血管動脈硬化疾病為目標。而致病的機制上則依巨噬細胞特有的巨噬細胞清除接受體 (macrophage scavenger receptor) 在正常及不正常的情形下,與其特定的結合子 (ligand) 相結合而調控產生出的細胞訊息傳導及訊息傳導分子和產物,如活性氧分子 (reactive oxygen species) inflammatory cytokines,造成對血管細胞在細胞及分子生物、生化上的影響;進而也將進行評估此接受體對整各生物體的關係。

  2. 是研究內毒素(lipopolysaccharide, endotoxin)誘發巨噬細胞產生的細胞訊息傳導及發炎性細胞激素(inflammatory cytokines):甲型腫瘤壞死因子(tumor necrosis factor-α)、第一白細胞介素(interleukin 1β)及其他發炎性反應(inflammatory responses)與對巨噬細胞本身以及對血管細胞各式各樣的細胞及分子生物、生化上影響,如細胞凋亡分子(apoptosis)、敗血症休克(septic shock)、菌血症(bacteremiasepticemia) 等等。

  3. 是人類基因體 (Human Genome)和蛋白質體 (Human Proteome)的探討,主題是以研究人類血管動脈硬化致病機轉及探討已知中草藥內具抗血管硬化的成分及藥效及可能治療血管硬化之機轉。同時我也探討人類在老化過程中,所產生各種基因表達的改變,進而可能產生出和老化相關聯的疾病。

        在我從事醫學生物基礎研究的同時,我也將我過去多年從事生物技術工業界的經驗,應用到目前發展醫學生物技術為主的實際應用這一方面,我的實驗室是專注於發展高敏感度的抗體、發展使用微矩列 (Microarray) 和蛋白質二維電泳法(2-D Electrophoresis)等等來鑑別診測血管疾病及老年退化性疾病。雖然這只是在初步性的實驗階段;但是,我們著手開始建立基本的檢測系統和方法,希望在未來能有所突破及應用。

       There are several major parts in my current researches. The first project : cellular-based and molecular-based biomedical researches, which related to human immunity and tumor/cancer. The second project: biotechnology relevant to potential drug research and development. The third project: biophotonic research on phagocytosis mechanism and processes.

        In essence, we currently focus on the following topics :

1.  To investigate and examine the cellular and molecular based researches on polysaccharides, proteins from Reishi (Ling-Zhi), which related to human immunity, sush as bacterial infection, tumorgenesis, as well as mice model, in vivo. We focus on the molecular activation of Toll-like receptor, TCR and BCR on macrophage, T cell, and B cell, respectively; and the consequent signaling outcomes of immunity reactions. Specifically, we investigate the upstream signaling elements, downstream mitogen activated protein kinases and the various cytokines induction. 

2.  Phagocytosis is essential in host defense against microorganism and microbial pathogens.  Phagocytosis is one kinds of endocytosis, which bind particle ligands to the specific receptors on phagocyte cell surface.  We focus on cellular and molecular mechanism for phagocytosis of macrophage with ligands (LPS, E. coli, Reishi, etc.), and investigate the role of MAPK including p38α in phagocytosis proceedings.  In addition, using bio-photonics tools we analyze the phagocytosis including actin assembly, pseudopod extension and phagosome closure in the real-time fashion. 

3.   Thrombomodulin (TM), a widely expressed glycoprotein receptor, physiologically plays a critical role in maintaining normal hemostatic balance with protein C system. Importantly, recent studies indicated TM functions as an anti-inflammatory molecule at several levels. We are interested in the investigation of both in vitro and in vivo effects of conditional expression of thrombomodulin protein on cells and on transgenic mice.  Specifically, we establish and use the transgenic mice of conditional mTM-EGFP expression in vivo in investigation of the TM function in eye phenotype abnormality or related to inflammation. We study effect of TM on cell culture model in vitro, in investigation of TM expression related to cell survival or apoptosis. In addition, we study molecular mechanism of suppression or promotion of tumor growth in SCID mice of injection with stable TM-transfected human melanoma cells.  

4.  Combining nano-biotechnology with biophotonics tools, we study the relationship between molecular structure and biological function of protein molecule including C-reactive protein (CRP), which a typical acute phase protein of inflammation related to the risk factor for cardiovascular diseases.  Recent medical research reports point out that CRP is highly correlated with coronary heart disease due to its concentration increase within a short period. Specifically, we develop the fiber-optic biosensor to detect CRP, and monitor protein binding kinetics, the association and dissociation rate constants of the reaction between FITC-conjugated monoclonal anti-human CRP antibody and the tested native CRP (nCRP) and modified CRP (mCRP).  On the other hand, we also work on the immuno-detection of nCRP and mCRP by using surface plasmon resonance (SPR) biosensing. The SPR biosensing provides a viable and accurate approach for the real-time evaluation of nCRP and mCRP levels, and is therefore of considerable benefit in clinical examinations of CPR.  

 研究計畫 (部分)
 

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【研究的主題】

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【研究的興趣】

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【研究員】【博士班】【碩士班】【助理】【行政人員】【工讀生

 

聯絡地址: 112 台北市北投區立農街二段155號  國立陽明大學 醫學生物技術研究所及醫事技術學系
No. 155, Sec. 2, Linong St., Beitou District, Taipei City 112, Taiwan (R.O.C.)  

Faculty of Biotechnology and Laboratory Science & Institute of Biotechnology in Medicine, National Yang-Ming University

Tel: (02) 2826-7252 Fax: (02) 2826-4092  E-MAIL: hyhsu@ym.edu.tw