Ching Ling Lien, PhD

Professor of Surgery and Stem Cell Biology & Regenerative Medicine

Director of the Heart Regeneration Research Laboratory, in the Department of Surgery at CHL

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Overview

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.

Publications

  • Developmental origin of a bipotential myocardial and smooth muscle cell precursor in the mammalian heart. Cell. 2006 Dec 15; 127(6):1137-50.. View in PubMed
  • Gene expression analysis of zebrafish heart regeneration. PLoS Biol. 2006 Aug; 4(8):e260.. View in PubMed
  • 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.. View in PubMed
  • Transcriptional profiling of caudal fin regeneration in zebrafish. ScientificWorldJournal. 2006 Jun 02; 6.. View in PubMed
  • fgf20 is essential for initiating zebrafish fin regeneration. Science. 2005 Dec 23; 310(5756):1957-60.. View in PubMed
  • 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.. View in PubMed
  • Target gene-specific modulation of myocardin activity by GATA transcription factors. Mol Cell Biol. 2004 Oct; 24(19):8519-28.. View in PubMed
  • Cardiac-specific activity of an Nkx2-5 enhancer requires an evolutionarily conserved Smad binding site. Dev Biol. 2002 Apr 15; 244(2):257-66.. View in PubMed
  • The Gas7 gene encodes two protein isoforms differentially expressed within the brain. Genomics. 1999 Nov 01; 61(3):298-306.. View in PubMed
  • Control of early cardiac-specific transcription of Nkx2-5 by a GATA-dependent enhancer. Development. 1999 Jan; 126(1):75-84.. View in PubMed