Ching Ling Lien, PhD

Professor of Surgery, Biochemistry & Molecular Medicine, and Stem Cell Biology & Regenerative Medicine

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

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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.


  • Protocol for the isolation and single-nuclei multiomic analyses of the human fetal epicardium STAR Protoc. 2024 Mar 21; 5(2):102973. . View in PubMed
  • Single-nuclei multiomic analyses identify human cardiac lymphatic endothelial cells associated with coronary arteries in the epicardium Cell Rep. 2023 Sep 26; 42(9):113106. . View in PubMed
  • Methods for dynamic and whole volume imaging of the zebrafish heart Dev Biol. 2023 12; 504:75-85. . View in PubMed
  • Heterogeneous pdgfrb+ cells regulate coronary vessel development and revascularization during heart regeneration Development. 2022 02 15; 149(4). . View in PubMed
  • Intramyocardial Injection for the Study of Cardiac Lymphatic Function in Zebrafish J Vis Exp. 2022 09 20; (187). . View in PubMed
  • Craniofacial and cardiac defects in chd7 zebrafish mutants mimic CHARGE syndrome Front Cell Dev Biol. 2022; 10:1030587. . View in PubMed
  • The Lymphatic System in Zebrafish Heart Development, Regeneration and Disease Modeling J Cardiovasc Dev Dis. 2021 Feb 19; 8(2). . View in PubMed
  • GLUT1 overexpression enhances glucose metabolism and promotes neonatal heart regeneration Sci Rep. 2021 04 21; 11(1):8669. . View in PubMed
  • Apical Resection and Cryoinjury of Neonatal Mouse Heart Methods Mol Biol. 2021; 2158:23-32. . View in PubMed
  • Extended culture and imaging of normal and regenerating adult zebrafish hearts in a fluidic device Lab Chip. 2020 01 21; 20(2):274-284. . View in PubMed
  • Mononuclear diploid cardiomyocytes support neonatal mouse heart regeneration in response to paracrine IGF2 signaling Elife. 2020 03 13; 9. . View in PubMed
  • Monitoring of Adult Zebrafish Heart Regeneration Using High-Frequency Ultrasound Spectral Doppler and Nakagami Imaging Sensors (Basel). 2019 Sep 22; 19(19). . View in PubMed
  • Differential roles of insulin like growth factor 1 receptor and insulin receptor during embryonic heart development BMC Dev Biol. 2019 03 25; 19(1):5. . View in PubMed
  • Late developing cardiac lymphatic vasculature supports adult zebrafish heart function and regeneration Elife. 2019 11 08; 8. . View in PubMed
  • Coronary Vasculature in Cardiac Development and Regeneration J Cardiovasc Dev Dis. 2018 Dec 17; 5(4). . View in PubMed
  • Tunable assembly of protein-microdomains in living vertebrate embryos Adv Biosyst. 2018 10; 2(10). . View in PubMed
  • Corrigendum to “Inhibition of Fgf signaling in short bowel syndrome increases weight loss and epithelial proliferation” [surgery volume 161, number 3 (2017) 694-703]. Surgery. 2018 06; 163(6):1330-1331. . View in PubMed
  • Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration Nat Genet. 2017 Sep; 49(9):1346-1353. . View in PubMed
  • Collagenolytic Activity Is Associated with Scar Resolution in Zebrafish Hearts after Cryoinjury J Cardiovasc Dev Dis. 2017 Feb 24; 4(1). . View in PubMed
  • Intestinal adaptation in proximal and distal segments: Two epithelial responses diverge after intestinal separation Surgery. 2017 04; 161(4):1016-1027. . View in PubMed
  • Inhibition of Fgf signaling in short bowel syndrome increases weight loss and epithelial proliferation Surgery. 2017 03; 161(3):694-703. . View in PubMed
  • Epidermal growth factor suppresses intestinal epithelial cell shedding through a MAPK-dependent pathway J Cell Sci. 2017 01 01; 130(1):90-96. . View in PubMed
  • Short bowel syndrome results in increased gene expression associated with proliferation, inflammation, bile acid synthesis and immune system activation: RNA sequencing a zebrafish SBS model BMC Genomics. 2017 01 25; 18(1):23. . View in PubMed
  • Recent advancements in understanding endogenous heart regeneration-insights from adult zebrafish and neonatal mice Semin Cell Dev Biol. 2016 10; 58:34-40. . View in PubMed
  • Adult zebrafish intestine resection: a novel model of short bowel syndrome, adaptation, and intestinal stem cell regeneration Am J Physiol Gastrointest Liver Physiol. 2015 Aug 01; 309(3):G135-45. . View in PubMed
  • CXCL12 Signaling Is Essential for Maturation of the Ventricular Coronary Endothelial Plexus and Establishment of Functional Coronary Circulation Dev Cell. 2015 May 26; 33(4):469-77. . View in PubMed
  • Chemokine-guided angiogenesis directs coronary vasculature formation in zebrafish Dev Cell. 2015 May 26; 33(4):442-54. . View in PubMed
  • Dry-contact microelectrode membranes for wireless detection of electrical phenotypes in neonatal mouse hearts Biomed Microdevices. 2015 Apr; 17(2):40. . View in PubMed
  • Differential regenerative capacity of neonatal mouse hearts after cryoinjury Dev Biol. 2015 Mar 01; 399(1):91-99. . View in PubMed
  • Extracardiac control of embryonic cardiomyocyte proliferation and ventricular wall expansion Cardiovasc Res. 2015 Mar 01; 105(3):271-8. . View in PubMed
  • High-frequency dual mode pulsed wave Doppler imaging for monitoring the functional regeneration of adult zebrafish hearts J R Soc Interface. 2015 Feb 06; 12(103). . View in PubMed
  • Shear stress-activated Wnt-angiopoietin-2 signaling recapitulates vascular repair in zebrafish embryos Arterioscler Thromb Vasc Biol. 2014 Oct; 34(10):2268-75. . View in PubMed
  • Wearable multi-channel microelectrode membranes for elucidating electrophysiological phenotypes of injured myocardium Integr Biol (Camb). 2014 Aug; 6(8):789-95. . View in PubMed
  • Cardiac regeneration in model organisms Curr Treat Options Cardiovasc Med. 2014 Mar; 16(3):288. . View in PubMed
  • High frequency photoacoustic imaging for in vivo visualizing blood flow of zebrafish heart Opt Express. 2013 Jun 17; 21(12):14636-42. . View in PubMed
  • Ultrasound bio-microscopic image segmentation for evaluation of zebrafish cardiac function IEEE Trans Ultrason Ferroelectr Freq Control. 2013 Apr; 60(4):718-26. . View in PubMed
  • Igf Signaling is Required for Cardiomyocyte Proliferation during Zebrafish Heart Development and Regeneration PLoS One. 2013; 8(6):e67266. . View in PubMed
  • Pulse inversion chirp coded tissue harmonic imaging (PI-CTHI) of Zebrafish heart using high frame rate ultrasound biomicroscopy Ann Biomed Eng. 2013 Jan; 41(1):41-52. . View in PubMed
  • Moving domain computational fluid dynamics to interface with an embryonic model of cardiac morphogenesis PLoS One. 2013; 8(8):e72924. . View in PubMed
  • Heart repair and regeneration: recent insights from zebrafish studies Wound Repair Regen. 2012 Sep-Oct; 20(5):638-46. . View in PubMed
  • Acoustic radiation force impulse (ARFI) imaging of zebrafish embryo by high-frequency coded excitation sequence Ann Biomed Eng. 2012 Apr; 40(4):907-15. . View in PubMed
  • In vitro culture of epicardial cells from adult zebrafish heart on a fibrin matrix Nat Protoc. 2012 Jan 19; 7(2):247-55. . View in PubMed
  • Restraint of angiogenesis by zinc finger transcription factor CTCF-dependent chromatin insulation Proc Natl Acad Sci U S A. 2011 Sep 13; 108(37):15231-6. . View in PubMed
  • PDGF signaling is required for epicardial function and blood vessel formation in regenerating zebrafish hearts Proc Natl Acad Sci U S A. 2010 Oct 05; 107(40):17206-10. . View in PubMed
  • Platelet-derived growth factor receptor beta is critical for zebrafish intersegmental vessel formation PLoS One. 2010 Jun 25; 5(6):e11324. . View in PubMed
  • Micro-electrocardiograms to study post-ventricular amputation of zebrafish heart Ann Biomed Eng. 2009 May; 37(5):890-901. . View in PubMed
  • In vivo cardiac imaging of adult zebrafish using high frequency ultrasound (45-75 MHz) Ultrasound Med Biol. 2008 Jan; 34(1):31-9. . View in PubMed
  • 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 Suppl 1:38-54. . 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
  • The myogenic regulatory gene Mef2 is a direct target for transcriptional activation by Twist during Drosophila myogenesis Genes Dev. 1998 Feb 01; 12(3):422-34. . View in PubMed