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Ching Ling Lien, PhD

Title(s)Associate Professor Surgery and Biochemistry & Molecular Medicine
AddressCHL MailStop137
Off Campus
Los Angeles CA 90089
Phone+1 323 361 8377
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    Title(s)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.

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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help. to make corrections and additions.
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    Altmetrics Details PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Apical Resection and Cryoinjury of Neonatal Mouse Heart. Methods Mol Biol. 2021; 2158:23-32. Shen H, Darehzereshki A, Sucov HM, Lien CL. PMID: 32857362.
      View in: PubMed   Mentions:    Fields:    
    2. Mononuclear diploid cardiomyocytes support neonatal mouse heart regeneration in response to paracrine IGF2 signaling. Elife. 2020 Mar 13; 9. Shen H, Gan P, Wang K, Darehzereshki A, Wang K, Kumar SR, Lien CL, Patterson M, Tao G, Sucov HM. PMID: 32167474.
      View in: PubMed   Mentions:    Fields:    
    3. Extended culture and imaging of normal and regenerating adult zebrafish hearts in a fluidic device. Lab Chip. 2020 01 21; 20(2):274-284. Yip JK, Harrison M, Villafuerte J, Fernandez GE, Petersen AP, Lien CL, McCain ML. PMID: 31872200.
      View in: PubMed   Mentions:    Fields:    
    4. Late developing cardiac lymphatic vasculature supports adult zebrafish heart function and regeneration. Elife. 2019 11 08; 8. Harrison MR, Feng X, Mo G, Aguayo A, Villafuerte J, Yoshida T, Pearson CA, Schulte-Merker S, Lien CL. PMID: 31702553.
      View in: PubMed   Mentions: 8     Fields:    Translation:HumansAnimals
    5. Monitoring of Adult Zebrafish Heart Regeneration Using High-Frequency Ultrasound Spectral Doppler and Nakagami Imaging. Sensors (Basel). 2019 Sep 22; 19(19). Yeo S, Yoon C, Lien CL, Song TK, Shung KK. PMID: 31546705.
      View in: PubMed   Mentions: 1     Fields:    Translation:Animals
    6. 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. Wang K, Shen H, Gan P, Cavallero S, Kumar SR, Lien CL, Sucov HM. PMID: 30909860.
      View in: PubMed   Mentions: 3     Fields:    Translation:AnimalsCells
    7. Coronary Vasculature in Cardiac Development and Regeneration. J Cardiovasc Dev Dis. 2018 Dec 17; 5(4). Kapuria S, Yoshida T, Lien CL. PMID: 30563016.
      View in: PubMed   Mentions:
    8. Tunable assembly of protein-microdomains in living vertebrate embryos. Adv Biosyst. 2018 10; 2(10). Li Z, Tyrpak DR, Lien CL, MacKay JA. PMID: 31840042.
      View in: PubMed   Mentions:
    9. 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. Schall KA, Holoyda KA, Isani M, Lien CL, Alam DA, Grikscheit TC. PMID: 29452701.
      View in: PubMed   Mentions:    Fields:    
    10. Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration. Nat Genet. 2017 Sep; 49(9):1346-1353. Patterson M, Barske L, Van Handel B, Rau CD, Gan P, Sharma A, Parikh S, Denholtz M, Huang Y, Yamaguchi Y, Shen H, Allayee H, Crump JG, Force TI, Lien CL, Makita T, Lusis AJ, Kumar SR, Sucov HM. PMID: 28783163.
      View in: PubMed   Mentions: 51     Fields:    Translation:AnimalsCells
    11. Collagenolytic Activity Is Associated with Scar Resolution in Zebrafish Hearts after Cryoinjury. J Cardiovasc Dev Dis. 2017 Feb 24; 4(1). Gamba L, Amin-Javaheri A, Kim J, Warburton D, Lien CL. PMID: 29367534.
      View in: PubMed   Mentions:
    12. 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. PMID: 28118819.
      View in: PubMed   Mentions: 3     Fields:    Translation:Animals
    13. Intestinal adaptation in proximal and distal segments: Two epithelial responses diverge after intestinal separation. Surgery. 2017 04; 161(4):1016-1027. PMID: 28011012.
      View in: PubMed   Mentions: 1     Fields:    Translation:Animals
    14. Inhibition of Fgf signaling in short bowel syndrome increases weight loss and epithelial proliferation. Surgery. 2017 03; 161(3):694-703. PMID: 27771159.
      View in: PubMed   Mentions: 1     Fields:    Translation:AnimalsCells
    15. Recent advancements in understanding endogenous heart regeneration-insights from adult zebrafish and neonatal mice. Semin Cell Dev Biol. 2016 10; 58:34-40. PMID: 27132022.
      View in: PubMed   Mentions: 7     Fields:    Translation:AnimalsCells
    16. Epidermal growth factor suppresses intestinal epithelial cell shedding through a MAPK-dependent pathway. J Cell Sci. 2017 01 01; 130(1):90-96. PMID: 27026527.
      View in: PubMed   Mentions: 6     Fields:    Translation:AnimalsCells
    17. 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. PMID: 26089336.
      View in: PubMed   Mentions: 8     Fields:    Translation:HumansAnimalsCells
    18. Chemokine-guided angiogenesis directs coronary vasculature formation in zebrafish. Dev Cell. 2015 May 26; 33(4):442-54. PMID: 26017769.
      View in: PubMed   Mentions: 43     Fields:    Translation:AnimalsCells
    19. 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. PMID: 26017771.
      View in: PubMed   Mentions: 24     Fields:    Translation:AnimalsCells
    20. Dry-contact microelectrode membranes for wireless detection of electrical phenotypes in neonatal mouse hearts. Biomed Microdevices. 2015 Apr; 17(2):40. PMID: 25749638.
      View in: PubMed   Mentions: 3     Fields:    Translation:Animals
    21. 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). PMID: 25505135.
      View in: PubMed   Mentions: 8     Fields:    Translation:Animals
    22. Extracardiac control of embryonic cardiomyocyte proliferation and ventricular wall expansion. Cardiovasc Res. 2015 Mar 01; 105(3):271-8. PMID: 25560321.
      View in: PubMed   Mentions: 13     Fields:    Translation:AnimalsCells
    23. Differential regenerative capacity of neonatal mouse hearts after cryoinjury. Dev Biol. 2015 Mar 01; 399(1):91-99. PMID: 25555840.
      View in: PubMed   Mentions: 27     Fields:    Translation:AnimalsCells
    24. Shear stress-activated Wnt-angiopoietin-2 signaling recapitulates vascular repair in zebrafish embryos. Arterioscler Thromb Vasc Biol. 2014 Oct; 34(10):2268-75. PMID: 25147335.
      View in: PubMed   Mentions: 19     Fields:    Translation:HumansAnimalsCells
    25. Wearable multi-channel microelectrode membranes for elucidating electrophysiological phenotypes of injured myocardium. Integr Biol (Camb). 2014 Aug; 6(8):789-95. PMID: 24945366.
      View in: PubMed   Mentions: 12     Fields:    Translation:Animals
    26. Cardiac regeneration in model organisms. Curr Treat Options Cardiovasc Med. 2014 Mar; 16(3):288. PMID: 24496965.
      View in: PubMed   Mentions:
    27. Moving domain computational fluid dynamics to interface with an embryonic model of cardiac morphogenesis. PLoS One. 2013; 8(8):e72924. PMID: 24009714.
      View in: PubMed   Mentions: 21     Fields:    Translation:Animals
    28. Igf Signaling is Required for Cardiomyocyte Proliferation during Zebrafish Heart Development and Regeneration. PLoS One. 2013; 8(6):e67266. PMID: 23840646.
      View in: PubMed   Mentions: 49     Fields:    Translation:AnimalsCells
    29. High frequency photoacoustic imaging for in vivo visualizing blood flow of zebrafish heart. Opt Express. 2013 Jun 17; 21(12):14636-42. PMID: 23787651.
      View in: PubMed   Mentions: 4     Fields:    Translation:Animals
    30. Ultrasound bio-microscopic image segmentation for evaluation of zebrafish cardiac function. IEEE Trans Ultrason Ferroelectr Freq Control. 2013 Apr; 60(4):718-26. PMID: 23549532.
      View in: PubMed   Mentions: 2     Fields:    Translation:Animals
    31. 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. PMID: 22930467.
      View in: PubMed   Mentions: 4     Fields:    Translation:Animals
    32. Heart repair and regeneration: recent insights from zebrafish studies. Wound Repair Regen. 2012 Sep-Oct; 20(5):638-46. PMID: 22818295.
      View in: PubMed   Mentions: 25     Fields:    Translation:HumansAnimalsCells
    33. In vitro culture of epicardial cells from adult zebrafish heart on a fibrin matrix. Nat Protoc. 2012 Jan 19; 7(2):247-55. PMID: 22262006.
      View in: PubMed   Mentions: 14     Fields:    Translation:Animals
    34. Acoustic radiation force impulse (ARFI) imaging of zebrafish embryo by high-frequency coded excitation sequence. Ann Biomed Eng. 2012 Apr; 40(4):907-15. PMID: 22101757.
      View in: PubMed   Mentions: 9     Fields:    Translation:Animals
    35. 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. 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. PMID: 21896759.
      View in: PubMed   Mentions: 11     Fields:    Translation:HumansAnimalsCells
    36. 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. Kim J, Wu Q, Zhang Y, Wiens KM, Huang Y, Rubin N, Shimada H, Handin RI, Chao MY, Tuan TL, Starnes VA, Lien CL. PMID: 20858732.
      View in: PubMed   Mentions: 83     Fields:    Translation:AnimalsCells
    37. Platelet-derived growth factor receptor beta is critical for zebrafish intersegmental vessel formation. PLoS One. 2010 Jun 25; 5(6):e11324. Wiens KM, Lee HL, Shimada H, Metcalf AE, Chao MY, Lien CL. PMID: 20593033.
      View in: PubMed   Mentions: 17     Fields:    Translation:Animals
    38. Micro-electrocardiograms to study post-ventricular amputation of zebrafish heart. Ann Biomed Eng. 2009 May; 37(5):890-901. Sun P, Zhang Y, Yu F, Parks E, Lyman A, Wu Q, Ai L, Hu CH, Zhou Q, Shung K, Lien CL, Hsiai TK. PMID: 19280341.
      View in: PubMed   Mentions: 26     Fields:    Translation:Animals
    39. In vivo cardiac imaging of adult zebrafish using high frequency ultrasound (45-75 MHz). Ultrasound Med Biol. 2008 Jan; 34(1):31-9. Sun L, Lien CL, Xu X, Shung KK. PMID: 17825980.
      View in: PubMed   Mentions: 33     Fields:    Translation:Animals
    40. Developmental origin of a bipotential myocardial and smooth muscle cell precursor in the mammalian heart. Cell. 2006 Dec 15; 127(6):1137-50. Wu SM, Fujiwara Y, Cibulsky SM, Clapham DE, Lien CL, Schultheiss TM, Orkin SH. PMID: 17123591.
      View in: PubMed   Mentions: 209     Fields:    Translation:AnimalsCells
    41. Gene expression analysis of zebrafish heart regeneration. PLoS Biol. 2006 Aug; 4(8):e260. Lien CL, Schebesta M, Makino S, Weber GJ, Keating MT. PMID: 16869712.
      View in: PubMed   Mentions: 107     Fields:    Translation:AnimalsCells
    42. 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. Xin M, Davis CA, Molkentin JD, Lien CL, Duncan SA, Richardson JA, Olson EN. PMID: 16847256.
      View in: PubMed   Mentions: 74     Fields:    Translation:HumansAnimals
    43. Transcriptional profiling of caudal fin regeneration in zebrafish. ScientificWorldJournal. 2006 Jun 02; 6 Suppl 1:38-54. Schebesta M, Lien CL, Engel FB, Keating MT. PMID: 17205186.
      View in: PubMed   Mentions: 40     Fields:    Translation:AnimalsCells
    44. fgf20 is essential for initiating zebrafish fin regeneration. Science. 2005 Dec 23; 310(5756):1957-60. Whitehead GG, Makino S, Lien CL, Keating MT. PMID: 16373575.
      View in: PubMed   Mentions: 97     Fields:    Translation:Animals
    45. 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. Makino S, Whitehead GG, Lien CL, Kim S, Jhawar P, Kono A, Kawata Y, Keating MT. PMID: 16204379.
      View in: PubMed   Mentions: 26     Fields:    Translation:AnimalsCells
    46. Target gene-specific modulation of myocardin activity by GATA transcription factors. Mol Cell Biol. 2004 Oct; 24(19):8519-28. Oh J, Wang Z, Wang DZ, Lien CL, Xing W, Olson EN. PMID: 15367672.
      View in: PubMed   Mentions: 22     Fields:    Translation:AnimalsCells
    47. Cardiac-specific activity of an Nkx2-5 enhancer requires an evolutionarily conserved Smad binding site. Dev Biol. 2002 Apr 15; 244(2):257-66. Lien CL, McAnally J, Richardson JA, Olson EN. PMID: 11944935.
      View in: PubMed   Mentions: 34     Fields:    Translation:HumansAnimalsCells
    48. The Gas7 gene encodes two protein isoforms differentially expressed within the brain. Genomics. 1999 Nov 01; 61(3):298-306. Lazakovitch EM, She BR, Lien CL, Woo WM, Ju YT, Lin-Chao S. PMID: 10552931.
      View in: PubMed   Mentions: 5     Fields:    Translation:AnimalsCells
    49. Control of early cardiac-specific transcription of Nkx2-5 by a GATA-dependent enhancer. Development. 1999 Jan; 126(1):75-84. Lien CL, Wu C, Mercer B, Webb R, Richardson JA, Olson EN. PMID: 9834187.
      View in: PubMed   Mentions: 91     Fields:    Translation:AnimalsCells
    50. 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. Cripps RM, Black BL, Zhao B, Lien CL, Schulz RA, Olson EN. PMID: 9450935.
      View in: PubMed   Mentions: 46     Fields:    Translation:AnimalsCells
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