5th International Symposium on Nanomanufacturing
Singapore
HIGH CONTENT IMAGE BASED PLATFORM FOR SCREENING ANTIFIBROTIC DRUGS
BAI-XUE ZHENG
Singapore-MIT Alliance, E4-04-10, 4 Engineering Drive, Singapore 117576
SER-MIEN CHIA
Singapore-MIT Alliance, E4-04-10, 4 Engineering Drive, Singapore 117576
FOONG-YEE KUAN
Department of Physiology, National University of Singapore, Singapore 117597
HANRY YU
Singapore-MIT Alliance, E4-04-10, 4 Engineering Drive, Singapore 117576
Department of Physiology, National University of Singapore, Singapore 117597
Institute of Bioengineering and Nanotechnology, A*STAR, Singapore 138669
Hepatic stellate cell (HSC) is a major cell type responsible for liver fibrosis by secreting extra
cellular matrix (ECM) such as collagen type I, III and IV in its activated form (Friedman et al.
1985). Transforming growth factor b (TGF-beta) was found to be a key growth factor in the
fibrogenesis process and for hepatic stellate cell activation (Gressner et al. 2002). Recently our
group has demonstrated that thrombospondin-1 is the key activator of latent TGF-beta
(unpublished data). Thus regulation of thrombospondin-1 is important in controlling fibrosis
progression and can potentially lead to fibrosis resolution. My research focus is to develop an
image-based drug screening platform for screening drugs that target thrombospondin-1 in the
hepatic stellate cells (primary HSC and human hepatic stellate cell line LX2), which potentially
lead to fibrosis resolution and to use single cell analysis approach to gain a better understanding of
the role thrombospondin-1 plays in the TGF-beta signaling pathway in HSC cells. Image based
analysis on fibrogenesis markers such as TIMP, MMP and collagen and key proteins in the TGFbeta signaling pathway which are up- or down-stream of thrombospondin-1, such as
thrombospondin-1 receptor, TGF-beta and Smad will be carried out followed by feature extraction
and statistical analysis (Perlman et al., 2004).
Acknowledgments, appendices, and references
This work is supported by the Computational and Systems Biology program under SingaporeMIT Alliance.
REFERENCES
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