Research

研究大綱/Research Theme

我們專注探討生物分子如何利用不同的結構及動態變化，在細胞內執行不同的功能，為了了解奈米尺寸下分子結構的細微變化，實驗室最主要利用核磁共振光譜 (Nuclear Magnetic Resonance) 及相關生物化技術，探討結構生物學 (Structure Biology) 的奧秘。目前實驗室儀器包含 Bruker 850MHz（台灣最高磁場），600MHz，500MHz 等三部核磁共振儀。

實驗室目前的研究題材包含三個大方向，生物分子與細胞表面醣類的辨識機制，抗血管新生趨化素的抗癌功能研究，膜蛋白研究技術發展。

1. 生物分子與細胞表面醣類的辨識機制：

My lab focuses on the hepatoma-derived growth factor, HDGF (肝癌衍生因子) and identified its N-terminal conserved PWWP/HATH domain as a heparin/heparan sulfate (醣肝素)-binding domain. We established its biological significance that HDGF entries the cell through the recognition between heparan sulfate and the PWWP/HATH domain. Meanwhile, the exogenous HDGF treatment regulates not only growth activity but also cell migration. Thus, the result strengthened the significance of membrane surface carbohydrate on HDGF. We also study the carbohydrate-binding lectins found in horseshoe carb (鱟). We are planning to understand the function and structure relationship and further develop the molecules to antimicrobial molecule (抗菌分子).

2. 抗血管新生趨化素的抗癌功能研究：

Angiogenesis inhibition (抗血管新生) has lead to impressive results in inhibiting a variety of human cancers in clinical trials. We studied structural and functional relationship of an anti-angiogenic chemokine (抗血管新生趨化素), CXCL4 and CXCL4L1. Notable, the recently isolated variant, CXCL4L1, is with much significant anti-angiogenic activity. In our current study, we show that the C-terminal helix orientation protrudes into the aqueous space. The unique helix orientation modifies the shape and surface properties. The alternative C-terminal helix conformation could be used in new anti-cancer strategy.

3. 膜蛋白研究技術發展：

Membrane protein (膜蛋白) remains one of the most challenge projects in structure biology. We are interested in developing a method in dealing membrane protein NMR study. My lab uses intein protein ligase (內含子蛋白) to assist the preparation of segmental-isotope-labeled protein. We employed protein circular permutation (環狀剪切) prediction to design stable intein in resisting the denaturation condition induced by of urea and detergents. The great chemical tolerance extends the usage to perform protein ligation for membrane protein. We are testing the intein-derived method for NMR membrane protein study.