Faculty

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Ching Ling Lien, PhD
Assistant Professor of Surgery
Pediatrics
CHL MailStop137 Off Campus Los Angeles
+1 323 361 8377

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

Rubin N, Harrison MR, Krainock M, Kim R, Lien CL. Recent advancements in understanding endogenous heart regeneration-insights from adult zebrafish and neonatal mice. Semin Cell Dev Biol. 2016 Oct; 58:34-40. View in: PubMed

Miguel JC, Maxwell AA, Hsieh JJ, Harnisch LC, Al Alam D, Polk DB, Lien CL, Watson AJ, Frey MR. Epidermal growth factor suppresses intestinal epithelial cell shedding through a MAPK-dependent pathway. J Cell Sci. 2016 Mar 29. View in: PubMed

Cavallero S, Shen H, Yi C, Lien CL, Kumar SR, Sucov HM. 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

Zhao Y, Cao H, Beebe T, Zhang H, Zhang X, Chang H, Scremin O, Lien CL, Tai YC, Hsiai TK. Dry-contact microelectrode membranes for wireless detection of electrical phenotypes in neonatal mouse hearts. Biomed Microdevices. 2015 Apr; 17(2):9912. View in: PubMed

Shen H, Cavallero S, Estrada KD, Sandovici I, Kumar SR, Makita T, Lien CL, Constancia M, Sucov HM. Extracardiac control of embryonic cardiomyocyte proliferation and ventricular wall expansion. Cardiovasc Res. 2015 Mar 1; 105(3):271-8. View in: PubMed

Darehzereshki A, Rubin N, Gamba L, Kim J, Fraser J, Huang Y, Billings J, Mohammadzadeh R, Wood J, Warburton D, Kaartinen V, Lien CL. Differential regenerative capacity of neonatal mouse hearts after cryoinjury. Dev Biol. 2015 Mar 1; 399(1):91-9. View in: PubMed

Kang BJ, Park J, Kim J, Kim HH, Lee C, Hwang JY, Lien CL, Shung KK. High-frequency dual mode pulsed wave Doppler imaging for monitoring the functional regeneration of adult zebrafish hearts. J R Soc Interface. 2015 Feb 6; 12(103). View in: PubMed

Li R, Beebe T, Jen N, Yu F, Takabe W, Harrison M, Cao H, Lee J, Yang H, Han P, Wang K, Shimizu H, Chen J, Lien CL, Chi NC, Hsiai TK. 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

Cao H, Yu F, Zhao Y, Zhang X, Tai J, Lee J, Darehzereshki A, Bersohn M, Lien CL, Chi NC, Tai YC, Hsiai TK. Wearable multi-channel microelectrode membranes for elucidating electrophysiological phenotypes of injured myocardium. Integr Biol (Camb). 2014 Jul 21; 6(8):789-95. View in: PubMed

Gamba L, Harrison M, Lien CL. Cardiac regeneration in model organisms. Curr Treat Options Cardiovasc Med. 2014 Mar; 16(3):288. View in: PubMed

Park J, Cummins TM, Harrison M, Lee J, Zhou Q, Lien CL, Shung KK. 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

Zhou X, Sun L, Yu Y, Qiu W, Lien CL, Shung KK, Yu W. 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

Huang Y, Harrison MR, Osorio A, Kim J, Baugh A, Duan C, Sucov HM, Lien CL. Igf Signaling is Required for Cardiomyocyte Proliferation during Zebrafish Heart Development and Regeneration. PLoS One. 2013; 8(6):e67266. View in: PubMed

Lee J, Moghadam ME, Kung E, Cao H, Beebe T, Miller Y, Roman BL, Lien CL, Chi NC, Marsden AL, Hsiai TK. Moving domain computational fluid dynamics to interface with an embryonic model of cardiac morphogenesis. PLoS One. 2013; 8(8):e72924. View in: PubMed

Park J, Huang Y, Chen R, Lee J, Cummins TM, Zhou Q, Lien CL, Shung KK. 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

Lien CL, Harrison MR, Tuan TL, Starnes VA. Heart repair and regeneration: Recent insights from zebrafish studies. Wound Repair Regen. 2012 Sep; 20(5):638-46. View in: PubMed

Park J, Lee J, Lau ST, Lee C, Huang Y, Lien CL, Kirk Shung K. 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

Kim J, Rubin N, Huang Y, Tuan TL, Lien CL. In vitro culture of epicardial cells from adult zebrafish heart on a fibrin matrix. Nat Protoc. 2012; 7(2):247-55. View in: PubMed

Tang M, Chen B, Lin T, Li Z, Pardo C, Pampo C, Chen J, Lien CL, Wu L, Ai L, Wang H, Yao K, Oh SP, Seto E, Smith LE, Siemann DW, Kladde MP, Cepko CL, Lu J. 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

Kim J, Wu Q, Zhang Y, Wiens KM, Huang Y, Rubin N, Shimada H, Handin RI, Chao MY, Tuan TL, Starnes VA, Lien CL. PDGF signaling is required for epicardial function and blood vessel formation in regenerating zebrafish hearts. Proc Natl Acad Sci U S A. 2010 Oct 5; 107(40):17206-10. View in: PubMed

Wiens KM, Lee HL, Shimada H, Metcalf AE, Chao MY, Lien CL. Platelet-derived growth factor receptor beta is critical for zebrafish intersegmental vessel formation. PLoS One. 2010; 5(6):e11324. View in: PubMed

Sun P, Zhang Y, Yu F, Parks E, Lyman A, Wu Q, Ai L, Hu CH, Zhou Q, Shung K, Lien CL, Hsiai TK. Micro-electrocardiograms to study post-ventricular amputation of zebrafish heart. Ann Biomed Eng. 2009 May; 37(5):890-901. View in: PubMed

Sun L, Lien CL, Xu X, Shung KK. 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

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. View in: 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. View in: 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. View in: PubMed

Schebesta M, Lien CL, Engel FB, Keating MT. Transcriptional profiling of caudal fin regeneration in zebrafish. ScientificWorldJournal. 2006; 6 Suppl 1:38-54. View in: 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. View in: 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. View in: 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. View in: PubMed

Lien CL, McAnally J, Richardson JA, Olson EN. 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

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