Researcher's Profile

SZE-KWAN LIN (林思洸)

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Research Outline      2017-09-08 22:13:09

一、Research Topic 1
From the viewpoint of metabolomics, the pathogenesis and new therapeutic strategies for three diseases: rheumatoid arthritis (RA), oral squamous cell carcinoma (OSCC), and bisphosphonate-related osteonecrosis of the jaw (BRONJ) are investigated.
1. We hypothesize that the three diseases are related to metabolic abnormalities in mitochondria. Multiple intermediate molecules in the metabolic reactions are involved in their pathogenic processes.
2. Most of our interested molecules are associated with mitochondrial metabolism, including those participating in glutaminolysis (eg. glutaminase), electron transportation chain (eg. Cytochrome C and P66), and fatty acids and cholesterol/oxysterol. Our researches focus on the expression of these intermediate molecules and their post-translation modifications, identification and quantitative/qualitative analysis of their constitutional isomers. Studies of this kind require techniques of bioinformatics/biomedical engineering, mass spectrometer, and protein film voltammetry. Establishment of cooperative relationships with other laboratories on these topics is our major task in recent years.
3. In vitro/in vivo correlation:
A. Establishment of disease animal models: The functional roles of particular genes are evaluated through induction of the three diseases in wild-type and gene knockout mice.
B. Gene therapy: The influences of overexpression of particular genes to the disease processes are observed after local gene delivery to the diseased sites in animal models.
C. To assess the effects of therapy, image analyses (micro-PET, micro-MRI, micro-CT and x-ray analyses by courtesy of Genomics Research Center, Academia Sinica) and histopathological studies are performed after animal sacrifice.
D. Orthopedic surgeons, pathologists and oral surgeons are comprised in our research team. Results of our in vitro and in vivo experiments are correlated with findings in clinical specimens of RA, OSCC and BRONJ. Clinical parameters and experimental data are compared.
E.By collaborating with Genomics Research Center, Academia Sinica, small molecule agonists or antagonists capable of modulating disease-related metabolic processes are developed to realize the therapeutic potential of our study results.
二、Research Topic 2
To develop a new biomembrane employed in guided bone regeneration, focusing on the enhancement of its stimulatory function on tissue regeneration and the improvement of material stiffness.
1. Our primary goal is to develop a biomembrane capable of recruiting stem cells to accomplish tissue regeneration.
2. Select genes that are pivotal to the chemotaxis of mesenchymal stem cells and their differentiation toward osteoblasts and fibroblasts. Genes are constructed in expression plasmids for the use in gene therapy. Our current gene of interest is stromal cell-derived factor (SDF)-1.
3. SDF-1 expression plasmid is packed with nanoparticles or polyethylenimine (PEI) to facilitate its transfection into target cells. The plasmid/carrier ratio most efficient for transfection is determined. The nanoparticle- or PEI-coated SDF-1 expression plasmid is tested in animal models to assess its stimulatory ability for bone and connective tissue regeneration.
4. Design a new biomembrane with enhanced rigidity to facilitate molding during bone augmentation procedures. The membrane is impregnated with nanoparticle- or PEI-coated SDF-1 plasmid. In addition to serving its traditional role as a tissue barrier, the new membrane has a functional capacity to promote the healing of gingiva and soft tissues and induce bone regeneration. Clinical values of the barrier membrane in guided bone regeneration can thus be enhanced.
5. The new biomembrane is developed in collaboration with the Department of Chemical Engineering, National Taiwan University. Construction of SDF-1 expression plasmid is accomplished and the experiment is now at the stage of determination of optimal parameters for PEI coating of plasmid.