Molecular mechanisms for decisions of cardiomyocyte fate.

Terminally differentiated fibroblasts and pluripotent stem cells can transdifferentiate or differentiate into cardiomyocytes. We attempt to unravel cellular and molecular mechanisms underlying the determination of cardiomyocyte cell fate. The goal is to design therapeutic strategies for heart regeneration. 

Laboratory models of cardiac development and disease.

We unravel molecular mechanisms governing heart development & disease. The goal is to search for potential cures by using induced pluripotent stem cells derived from heart disease patients and pre-clinical animal models.

Faculty

Kunhua Song
Associate Professor of Medicine,
Davison of Cardiology,
Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology. Training Faculty:

• Molecular and Cellular Pharmacology Graduate Program
• Cell Biology, Stem Cells and Development Graduate Program 
• Medical Scientist Training Program (MD/PhD) 

Congwu Chi
Assistant Professor – Research
BS, Shandong University, Shandong
PhD, Fudan University, Shanghai

Research Assistant

Zhen Zhang
BA, Central China Normal University, Hunan
MA, Shanghai University, Shanghai

GSIP Student

Brett Li
BS, University of Colorado – Boulder, Colorado

Past Lab Members

Ellis Aune
University of Colorado-Boulder, class of 2018

Pilar Londono
BS - Metropolitan State University of Denver
MS University of Colorado – Denver

Betty Bai
Cornell University, class of 2022

Phoebe Dillon
University of Denver, class of 2022

Yingqiong Cao
BS, Dalian University of Technology, Dalian
MS, China Agricultural University, Beijing

Yuanbiao Zhao
BS, Wuhan University, Wuhan
PhD, China Agricultural University, Beijing

Walter Knight
BA, Cornell University, Ithaca, NY
PhD, University of Rochester, Rochester, NY

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. 2023 Jun 5;26(7):107012. doi: 10.1016/j.isci.2023.107012. PMID: 37360690.

Waugh KA, Minter R, Baxter J, Chi C, Galbraith MD, Tuttle KD, Eduthan NP, Kinning KT, Andrysik Z, Araya P, Dougherty H, Dunn LN, Ludwig M, Schade KA, Tracy D, Smith KP, Granrath RE, Busquet N, Khanal S, Anderson RD, Cox LL, Estrada BE, Rachubinski AL, Lyford HR, Britton EC, Fantauzzo KA, Orlicky DJ, Matsuda JL, Song K, Cox TC, Sullivan KD, Espinosa JM. Triplication of the interferon receptor locus contributes to hallmarks of Down syndrome in a mouse model. Nat Genet. 2023 Jun;55(6):1034-1047. doi: 10.1038/s41588-023-01399-7. Epub 2023 Jun 5. PMID: 37277650.

Chi C, Song K. Cellular reprogramming of fibroblasts in heart regeneration. J Mol Cell Cardiol. 2023 Jul;180:84-93. doi: 10.1016/j.yjmcc.2023.03.009. Epub 2023 Mar 23. PMID: 36965699.

Tatavosian R, Donovan MG, Galbraith MD, Duc HN, Szwarc MM, Joshi MU, Frieman A, Bilousova G, Cao Y, Smith KP, Song K, Rachubinski AL, Andrysik Z, Espinosa JM. Cell differentiation modifies the p53 transcriptional program through a combination of gene silencing and constitutive transactivation. Cell Death Differ. 2023 Jan 21. doi: 10.1038/s41418-023-01113-4. PMID: 36681780.

Hu W, Chi C, Song K, Zheng H. The molecular mechanism of sialic acid transport mediated by Sialin. Sci Adv. 2023 Jan 20;9(3):eade8346. doi: 10.1126/sciadv.ade8346. PMID: 36662855.

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. 2022 Aug 30;146(9):699-714. doi: 10.1161/CIRCULATIONAHA.121.058017. PMID: 35862102; PMCID: PMC9427731.

Klionsky DJ,… Song K…. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)¹. Autophagy. 2021 Jan;17(1):1-382.

Knight WE, Cao Y, Lin YH, Chi C, Bai B, Sparagna GC, Zhao Y, Du Y, Londono P, Reisz JA, Brown BC, Taylor MRG, Ambardekar AV, Cleveland JC Jr, McKinsey TA, Jeong MY, Walker LA, Woulfe KC, D'Alessandro A, Chatfield KC, Xu H, Bristow MR, Buttrick PM, Song K. Maturation of Pluripotent Stem Cell-Derived Cardiomyocytes Enables Modeling of Human Hypertrophic Cardiomyopathy. Stem Cell Reports. 2021 Mar 9;16(3):519-533.

Riching AS, Song K. Cardiac Regeneration: New Insights Into the Frontier of Ischemic Heart Failure Therapy. Front Bioeng Biotechnol. 2021 Jan 27;8:637538.

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. 2021 Apr;153:44-59.

Chi C, Riching AS, Song K. Lysosomal Abnormalities in Cardiovascular Disease. Int J Mol Sci. 2020 Jan 27;21(3):811.

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. Circ Res. 2019 Sep 13;125(7):662-677.

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. 2019 Jan 8;116(2):556-565.

Bagchi RA, Ferguson BS, Stratton MS, Hu T, Cavasin MA, Sun L, Lin YH, Liu D, Londono P, Song K, Pino MF, Sparks LM, Smith SR, Scherer PE, Collins S, Seto E, McKinsey TA. HDAC11 suppresses the thermogenic program of adipose tissue via BRD2. JCI Insight. 2018 Aug 9;3(15):e120159.

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 Dev. 2017 Sep 1;31(17):1770-1783.

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. Nat Commun. 2015 Sep 10;6:8243.

Du Bois P, Pablo Tortola C, Lodka D, Kny M, Schmidt F, Song K, Schmidt S, Bassel-Duby R, Olson EN, Fielitz J. Angiotensin II Induces Skeletal Muscle Atrophy by Activating TFEB-Mediated MuRF1 Expression. Circ Res. 2015 Aug 14;117(5):424-36.

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. 2014 Aug 5;111(31):11521-6.

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. 2013 Apr 2;110(14):5588-93. 2013

Nam YJ, Song K, Olson EN. Heart repair by cardiac reprogramming. Nat Med. 2013 Apr;19(4):413-5.

Song K, Nam YJ, Luo X, Qi X, Tan W, Huang GN, Acharya A, Smith CL, Tallquist MD, Neilson EG, Hill JA, Bassel-Duby R, Olson EN. Heart repair by reprogramming non-myocytes with cardiac transcription factors. Nature. 2012 May 13;485(7400):599-604.

Backs J, Song K, Bezprozvannaya S, Chang S, Olson EN. CaM kinase II selectively signals to histone deacetylase 4 during cardiomyocyte hypertrophy. J Clin Invest. 2006 Jul;116(7):1853-64.

Song K, Backs J, McAnally J, Qi X, Gerard RD, Richardson JA, Hill JA, Bassel-Duby R, Olson EN. The transcriptional coactivator CAMTA2 stimulates cardiac growth by opposing class II histone deacetylases. Cell. 2006 May 5;125(3):453-66.