Heart Institute

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* (MCOM Heart Institute FP)

Kunhua Song

Kunhua Song, PhD

Contact Info

Education

  • Ph.D., Genetics and Development, the University of Texas Southwestern Medical Center, 2007
  • B.S., Biology, Fudan University, 1996
  • M.S., Cell and Molecular Biology, the University of Arkansas, 2002
  • M.A., Immunology, Zhejiang University, 1999

Research Interests

  • Combining hiPSC technology with mouse models provides a powerful toolkit for dissecting complex cardiovascular diseases and developing novel therapeutic strategies. The ongoing projects in my lab are shown below.
  • 1. Congenital Heart Defects in Down Syndrome
  • Project Goals: Investigate how Down syndrome (DS) affects heart development and function. DS is associated with congenital heart defects (CHDs) such as atrioventricular septal defects and ventricular septal defects. We aim to identify novel therapeutic targets or drug repurposing strategies to correct or mitigate heart defects in DS and explore the role of specific genes or gene networks (e.g., DYRK1A) in heart development and disease.
  • • Approach:
  • o hiPSC Models: Derive cardiomyocytes from DS-hiPSCs to model heart defects and study how trisomy 21 influences cardiogenesis at the cellular level.
  • o Mouse Models: Use mouse models with trisomy 21 or gene editing to investigate DS-specific heart defects and their molecular mechanisms.
  • 2. Translational Research of Heart Failure
  • Project Goals: Understand the molecular mechanisms underlying heart failure and develop potential treatments. We aim to Investigate the impact of various stresses on cardiomyocyte contractility and viability and explore the efficacy of metabolic modulators or gene therapies to restore normal cardiac function.
  • • Approach:
  • o hiPSC Models: Generate cardiomyocytes and engineered heart tissue from patients to study stress and its effects on heart cells.
  • o Mouse Models: Use genetically modified mice to replicate cardiomyopathy/heart failure and test interventions.
  • 3. Molecular Mechanisms Underlying Cardiomyocyte Cell Fate Decision for Heart Regeneration
  • Project Goals: Uncover the factors that determine whether cardiomyocytes proliferate, differentiate, or undergo apoptosis, and leverage this understanding for heart regeneration. We aim to identify key regulators of cardiomyocyte cell fate commitment, cell cycle progression, and survival and develop strategies to enhance the regenerative capacity of the heart by manipulating signaling pathways or gene expression.
  • • Approach:
  • o hiPSC Models: Study how different conditions or genetic modifications influence the ability of hiPSC-derived cardiomyocytes and tissues to regenerate.
  • o Mouse Models: Investigate the role of specific genes or signaling pathways in the repopulation of cardiomyocytes.
  • o Gene Editing: Use CRISPR/Cas9 or other techniques to dissect the genes' function in cell fate decisions.

Recent Publications

  • Chi C, Knight WE, Riching AS, Zhang Z, Tatavosian R, Zhuang Y, Moldovan R, Rachubinski AL, Gao D, Xu H, Espinosa JM, Song K. Interferon hyperactivity impairs cardiogenesis in Down syndrome via downregulation of canonical Wnt signaling. iScience. 26(7) : 107012, 2023.
  • Waugh KA, Minter R, Baxter J, Chi C, Galbraith MD, Tuttle KD, ....Song K, Cox TC, Sullivan KD, Espinosa JM. Triplication of the interferon receptor locus contributes to hallmarks of Down syndrome in a mouse model. Nature Genetics. 55(6) : 1034-1047, 2023.
  • Hu W, Chi C, Song K, Zheng H. The molecular mechanism of sialic acid transport mediated by Sialin. Science Advances. 9(3) : eade8346, 2023.
  • Zhao Y, Riching AS, Knight WE, Chi C, Broadwell LJ, Du Y, Abdel-Hafiz M, Ambardekar AV, Irwin DC, Proenza C, Xu H, Leinwand LA, Walker LA, Woulfe KC, Bristow MR, Buttrick PM, Song K. Cardiomyocyte-Specific Long Noncoding RNA Regulates Alternative Splicing of the Triadin Gene in the Heart. Circulation. 146(9) : 699-714, 2022.
  • Knight WE, Cao Y, Lin YH, Chi C, Bai B, Sparagna GC, Zhao Y, Du Y, Londono P, .......Bristow MR, Buttrick PM, Song K Maturation of Pluripotent Stem Cell-Derived Cardiomyocytes Enables Modeling of Human Hypertrophic Cardiomyopathy. Stem Cell Reports. 16(3) : 519-533, 2021.
  • Riching AS, Danis E, Zhao Y, Cao Y, Chi C, Bagchi RA, Klein BJ, Xu H, Kutateladze TG, McKinsey TA, Buttrick PM, Song K. Suppression of canonical TGF-β signaling enables GATA4 to interact with H3K27me3 demethylase JMJD3 to promote cardiomyogenesis. J Mol Cell Cardiol. 153: 44-59, 2021.
  • Chi C, Leonard A, Knight WE, Beussman KM, Zhao Y, Cao Y, Londono P, Aune E, Trembley MA, Small EM, Jeong MY, Walker LA, Xu H, Sniadecki NJ, Taylor MR, Buttrick PM, Song K. LAMP-2B regulates human cardiomyocyte function by mediating autophagosome-lysosome fusion Proc Natl Acad Sci U S A. 116(2) : 556-565, 2019.
  • Zhao Y, Londono P, Cao Y, Sharpe EJ, Proenza C, O'Rourke R, Jones KL, Jeong MY, Walker LA, Buttrick PM, McKinsey TA, Song K High-efficiency reprogramming of fibroblasts into cardiomyocytes requires suppression of pro-fibrotic signalling Nature Communications. 6: 8243, 2015.
  • Song, Kunhua|Nam, Young-Jae|Luo, Xiang|Qi, Xiaoxia|Tan, Wei|Huang, Guo N.|Acharya, Asha|Smith, Christopher L.|Tallquist, Michelle D.|Neilson, Eric G.|Hill, Joseph A.|Bassel-Duby, Rhonda|Olson, Eric N. Heart repair by reprogramming non-myocytes with cardiac transcription factors Nature. 485(7400) : 599-604, 2012.
  • Stratton MS, Bagchi RA, Felisbino MB, Hirsch RA, Smith HE, Riching AS, Enyart BY, Koch KA, Cavasin MA, Alexanian M, Song K, Qi J, Lemieux ME, Srivastava D, Lam MPY, Haldar SM, Lin CY, McKinsey TA. Dynamic Chromatin Targeting of BRD4 Stimulates Cardiac Fibroblast Activation. Circulation Research. 125(7) : 662-677, 2019.
  • Zhou H, Morales MG, Hashimoto H, Dickson ME, Song K, Ye W, Kim MS, Niederstrasser H, Wang Z, Chen B, Posner BA, Bassel-Duby R, Olson EN. ZNF281 enhances cardiac reprogramming by modulating cardiac and inflammatory gene expression. Genes and Development. 31(17) : 770-1783, 2017.
  • Long C, Grueter CE, Song K, Qin S, Qi X, Kong YM, Shelton JM, Richardson JA, Zhang CL, Bassel-Duby R, Olson EN. Ataxia and Purkinje cell degeneration in mice lacking the CAMTA1 transcription factor Proc Natl Acad Sci U S A. 111(31) : 11521-6, 2014.
  • Nam YJ, Song K, Olson EN Heart repair by cardiac reprogramming. Nature Medicine. 19(4) : 413-5, 2013.
  • Nam YJ, Song K, Luo X, Daniel E, Lambeth K, West K, Hill JA, DiMaio JM, Baker LA, Bassel-Duby R, Olson EN. Reprogramming of human fibroblasts toward a cardiac fate. Proc Natl Acad Sci U S A.. 110(14) : 5588-93, 2013.
  • Chi C, Song K. Cellular reprogramming of fibroblasts in heart regeneration. J Mol Cell Cardiol.. 180: 84-93, 2023.
  • Riching AS, Song K. Cardiac Regeneration: New Insights Into the Frontier of Ischemic Heart Failure Therapy. Front Bioeng Biotechnol.. 8: 637538, 2021.