Professional Education

  • Doctor of Philosophy, Stanford University, CANBI-PHD (2013)
  • Bachelor of Medicine, National Taiwan University, Medicine (2009)
  • Doctor of Medicine, National Taiwan University (2009)


Journal Articles

  • Partitioning the heart: mechanisms of cardiac septation and valve development DEVELOPMENT Lin, C., Lin, C., Chen, C., Zhou, B., Chang, C. 2012; 139 (18): 3277-3299


    Heart malformations are common congenital defects in humans. Many congenital heart defects involve anomalies in cardiac septation or valve development, and understanding the developmental mechanisms that underlie the formation of cardiac septal and valvular tissues thus has important implications for the diagnosis, prevention and treatment of congenital heart disease. The development of heart septa and valves involves multiple types of progenitor cells that arise either within or outside the heart. Here, we review the morphogenetic events and genetic networks that regulate spatiotemporal interactions between the cells that give rise to septal and valvular tissues and hence partition the heart.

    View details for DOI 10.1242/dev.063495

    View details for Web of Science ID 000307925500003

    View details for PubMedID 22912411

  • The secondary heart field is a new site of calcineurin/Nfatc1 signaling for semilunar valve development JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY Lin, C., Lin, C., Chen, C., Chen, R. M., Zhou, B., Chang, C. 2012; 52 (5): 1096-1102


    Semilunar valve malformations are common human congenital heart defects. Bicuspid aortic valves occur in 2-3% of the population, and pulmonic valve stenosis constitutes 10% of all congenital heart disease in adults (Brickner et al., 2000) [1]. Semilunar valve defects cause valve regurgitation, stenosis, or calcification, leading to endocarditis or congestive heart failure. These complications often require prolonged medical treatment or surgical intervention. Despite the medical importance of valve disease, the regulatory pathways governing semilunar valve development are not entirely clear. In this report we investigated the spatiotemporal role of calcineurin/Nfatc1 signaling in semilunar valve development. We generated conditional knockout mice with calcineurin gene disrupted in various tissues during semilunar valve development. Our studies showed that calcineurin/Nfatc1 pathway signals in the secondary heart field (SHF) but not in the outflow tract myocardium or neural crest cells to regulate semilunar valve morphogenesis. Without SHF calcineurin/Nfatc1 signaling, the conal endocardial cushions-the site of prospective semilunar valve formation--first develop and then regress due to apoptosis, resulting in a striking phenotype with complete absence of the aortic and pulmonic valves, severe valve regurgitation, and perinatal lethality. This role of calcineurin/Nfatc1 signaling in the SHF is different from the requirement of calcineurin/Nfatc1 in the endocardium for semilunar valve formation (Chang et al., 2004) [2], indicating that calcineurin/Nfatc1 signals in multiple tissues to organize semilunar valve development. Also, our studies suggest distinct mechanisms of calcineurin/Nfat signaling for semilunar and atrioventricular valve morphogenesis. Therefore, we demonstrate a novel developmental mechanism in which calcineurin signals through Nfatc1 in the secondary heart field to promote semilunar valve morphogenesis, revealing a new supportive role of the secondary heart field for semilunar valve formation.

    View details for DOI 10.1016/j.yjmcc.2012.01.013

    View details for Web of Science ID 000303269400022

    View details for PubMedID 22300732

  • Rottlerin Inhibits Migration of Follicular Thyroid Carcinoma Cells by PKC delta-Independent Destabilization of the Focal Adhesion Complex JOURNAL OF CELLULAR BIOCHEMISTRY Lin, C., Lin, C., Chen, Y., Huang, S., Wang, S. 2010; 110 (2): 428-437


    This study examined the effect of rottlerin on the focal adhesion-mediated cell migration of CGTH W-2 human follicular thyroid carcinoma cells. Rottlerin (10 microM) resulted in decreased adhesion of CGTH W-2 cells to matrix substance, which was correlated with metastatic potential. Rottlerin treatment also resulted in a marked reduction in the migration of CGTH W-2 cells. Protein levels of integrin beta1, FAK, and paxillin were decreased by rottlerin. Consistent with this, immunostaining of FAK, vinculin, and paxillin revealed disassembly of the focal adhesions. Disruption of actin stress fibers was noted, which was compatible with reduced expression levels and activities of Rac-1 and Rho. The effect of rottlerin on cell migration was not attributable to inhibition of PKCdelta activity since siRNA knockdown of PKCdelta did not recapitulate the effects of rottlerin on cell adhesion and migration. Furthermore, activation of PKCdelta by phorbol esters failed to restore the rottlerin-inhibited migratory ability. The mitochondrial uncoupler, carbonylcyanide-4-(trifluoromethoxy)-phenylhydrazone, was able to mimic several rottlerin's effects. In summary, we demonstrated that rottlerin inhibits the migration of CGTH W-2 cells by disassembly of focal adhesion complexes in a PKCdelta-independent manner, and might play as a mitochondrial uncoupler role in these events.

    View details for DOI 10.1002/jcb.22555

    View details for Web of Science ID 000277482700018

    View details for PubMedID 20225271

  • Repeated Bacteremia with Subsequent Septic Arthritis Caused by Klebsiella pneumoniae Capsular Serotype K57 in a Patient with Diabetes CLINICAL INFECTIOUS DISEASES Lin, C., Lin, C., Li, W., Hsiue, H., Huang, Y., Ruan, S., Wang, J., Hsueh, P. 2009; 49 (8): 1284-1286

    View details for DOI 10.1086/605689

    View details for Web of Science ID 000270230100024

    View details for PubMedID 19780664

  • Macrophage activation increases the invasive properties of hepatoma cells by destabilization of the adherens junction FEBS LETTERS Lin, C., Lin, C., Chen, K., Wu, J., Huang, S., Wang, S. 2006; 580 (13): 3042-3050


    Tumor-associated macrophages play an important role in tumor progression, but whether they exert a tumor-progressive effect remains controversial. Here, we demonstrated that activated macrophage-conditioned medium (AMCM) obtained from RAW macrophages (RAW/AMCM) induced epithelial-mesenchymal transition (EMT) and stimulated the migratory and invasive activities of HepG2 cells, whereas control conditioned media had no effect. Epithelial-cadherin (E-cadherin) and beta-catenin staining patterns were altered at the adherens junctions by RAW/AMCM treatment, with an approximately 50% decrease in E-cadherin and beta-catenin in the cell membrane. Importantly, levels of beta-catenin-associated E-cadherin were also decreased. Following RAW/AMCM treatment, enhanced activation of c-Src was seen prior to increased tyrosine phosphorylation of beta-catenin, and this led to the destabilization of adherens junctions. Pretreatment of HepG2 cells with the Src kinase inhibitor, PP2, completely abolished the effects of RAW/AMCM on the EMT, migration, invasion, and expression and association of E-cadherin and beta-catenin. AMCMs obtained from human THP-1 monocytes and mouse peritoneal macrophages also caused disassembly of the adherens junctions and migration of HepG2 cells. Furthermore, inhibition of the epidermal growth factor receptor (EGFR) with gefitinib partially prevented the downregulation of E-cadherin and beta-catenin at the adherens junctions and migration behavior induced by RAW/AMCM. Our results suggest that activated macrophages have a tumor-progressive effect on HepG2 cells which involves the c-Src- and EGFR-dependent signaling cascades.

    View details for DOI 10.1016/j.febslet.2006.04.049

    View details for Web of Science ID 000238107400009

    View details for PubMedID 16678166

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