| Send E-mail to: clien@chla.usc.edu | |
| Telephone: 323-644-8377 | Fax: |
| Office: SRI 137 | Mail Code: 0000 OTH |
Education:
BS 1993 - National Taiwan University
MS 1995 - National Taiwan University
PhD 2001 - University of Texas, Southwestern Medical Center, Dallas
Postdoctoral Research Fellowship:
2006 Children's Hospital of Boston
Harvard Medical School
Started at USC: 2006
Research Topics: Developmental Biology, Cell Cycle, Growth & Proliferation, Cardiovascular & Skeletal Muscle Diseases, Gene Regulation/Transcription
Research Description
Heart disease is among the leading causes of death for both adults and children. Mammalian hearts have very limited regenerative capacity and heal by scarring and hypertrophy after heart injury, which results in decreased cardiac performance. By contrast, zebrafish have remarkable regenerative capacity. The molecular mechanisms of zebrafish heart regeneration are not understood. The goal of my lab is to define the molecular and cellular mechanisms of heart regeneration in zebrafish with the long-term goal of enhancing regenerative capacity and replacing defective tissues in diseased human hearts.
We use genetic and genomic approaches to dissect the process of zebrafish heart regeneration. Using gene expression profiling, we identified a set of genes that are differentially expressed during heart regeneration. We would like to address the following basic questions: How do these genes contribute to heart regeneration in zebrafish? Does regeneration recapitulate the developmental process? Are stem cells also involved in this regeneration process? The functions of these genes will be characterized in cultured cardiomyocytes in vitro, zebrafish embryos and regenerating hearts in vivo.
Most zebrafish genes are highly conserved with mammalian homologues. However, zebrafish can regenerate heart but mammals can’t. We would like to test the two possibilities that contribute to the incapability of regeneration: 1 mammalian hearts fail to express these genes upon injuries at the right time and place; 2. mammalian cardiomyocytes response to stimuli differently from zebrafish cardiomyocytes.
Our work may lead to discovery of important factors/pathways that can contribute to pharmaceutical or cellular therapies for ischemic or congenital heart diseases.
Selected Publications
Sun L, Lien CL, Shung KK. - IN VIVO CARDIAC IMAGING OF ADULT ZEBRAFISH USING HIGH FREQUENCY ULTRASOUND (45-75 MHz). - Ultrasound Med Biol [ 2007 ] Sep 6; . PubMed
Schebesta M, Lien CL, Engel FB, Keating MT. - Transcriptional profiling of caudal fin regeneration in zebrafish. - ScientificWorldJournal [ 2006 ] Jun 2;6 Suppl 1:38-54 . PubMed
Wu SM, Fujiwara Y, Cibulsky SM, Clapham DE, Lien CL, Schultheiss TM, Orkin SH. - Developmental origin of a bipotential myocardial and smooth muscle cell precursor in the mammalian heart. - Cell [ 2006 ] Dec 15;127(6):1137-50 . PubMed
Lien CL, Schebesta M, Makino S, Weber GJ, Keating MT. - Gene expression analysis of zebrafish heart regeneration. - PLoS Biol [ 2006 ] Aug;4(8):e260 . PubMed
Xin M, Davis CA, Molkentin JD, Lien CL, Duncan SA, Richardson JA, Olson EN. - A threshold of GATA4 and GATA6 expression is required for cardiovascular development. - Proc Natl Acad Sci U S A [ 2006 ] Jul 25;103(30):11189-94 . PubMed
Whitehead GG, Makino S, Lien CL, Keating MT. - fgf20 is essential for initiating zebrafish fin regeneration. - Science [ 2005 ] Dec 23;310(5756):1957-60 . PubMed
Makino S, Whitehead GG, Lien CL, Kim S, Jhawar P, Kono A, Kawata Y, Keating MT. - Heat-shock protein 60 is required for blastema formation and maintenance during regeneration. - Proc Natl Acad Sci U S A [ 2005 ] Oct 11;102(41):14599-604 . PubMed
Oh J, Wang Z, Wang DZ, Lien CL, Xing W, Olson EN. - Target gene-specific modulation of myocardin activity by GATA transcription factors. - Mol Cell Biol [ 2004 ] Oct;24(19):8519-28 . PubMed
