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Long-Sheng Song, MD, MS

Professor of Internal Medicine-Cardiovascular Medicine

Current Positions

  • Professor of Internal Medicine - Cardiovascular Medicine
  • Professor of Biochemistry and Molecular Biology
  • Edith King Pearson Chair in Cardiovascular Research

Education

  • MD, North China University of Science and Technology (formerly North China Coal Medical College), Tangshan, Hebei, China
  • MS, Kunming Medical University, Kunming, Yunnan, China
  • Postdoctoral Fellow, National Institute on Aging, NIH, Baltimore, Maryland, United States

Graduate Program Affiliations

Center, Program and Institute Affiliations

Research Interests

  • The long-term research interest in the Song laboratory is to elucidate the mechanisms underlying heart failure and cardiac arrhythmias, which are major public health problems world-wide. The goal of our research is to identify and define the mechanisms that lead to heart failure / arrhythmias and to develop therapeutic strategies for these diseases. To achieve this goal, we apply a multidisciplinary approach including high resolution confocal imaging, patch-clamp electrophysiology, biochemistry, cellular and molecular biology, as well as novel genetic mouse models developed in the lab. Our research projects are funded by National Heart, Lung and Blood Institute, the Department of Veterans Affairs, and the American Heart Association. The Song lab also actively collaborates with other labs and investigators within the University of Iowa and outside the campus.
  • investigators within the University of Iowa and outside the campus. In particular, we are interested in unraveling the novel functions of the E-C coupling structure protein junctophilin-2 in heart cells and its implications in these heart diseases. Work from the Song laboratory has established a new paradigm for heart failure development and progression by linking junctophilin-2 dysregulation to cardiomyocyte T-tubule ultrastructural remodeling and E-C coupling dysfunction (Song PNAS 2006; Wei Circ Res 2010; Guo PNAS 2014; Zhang Circulation 2014, among other original contributions). Furthermore, we have unraveled two distinct mechanisms underlying junctophilin-2 dysregulation: 1) proteolysis of junctophilin-2 by calpain (Wu JAHA 2014; Guo JBC 2015); and 2) mis-trafficking of junctophilin-2 to the cell periphery mediated by microtubule densification (Zhang Circulation 2014). Very recently, we made a major discovery that the E-C coupling structural protein junctophilin-2 encodes a stress-adaptive transcriptional regulator, which serves as an important protective mechanism in antagonizing pathological remodeling in response to cardiac stress (Guo Science 2018, link for full article). We will continue our endeavor in investigating the novel functions of junctophilin-2, and its therapeutic potential for treating heart failure and arrhythmias.

Selected Publications

  • Wang J, Shi Q, Wang Y, Dawson LW, Ciampa G, Zhao W, Zhang G, Chen B, Weiss RM, Grueter CE, Hall DD, Song LS. (2022) Gene Therapy With the N-Terminus of Junctophilin-2 Improves Heart Failure in Mice. Circ Res. 2022 Mar 23;CIRCRESAHA121320680. PMID: 35317607 PMCID: PMC9050933. doi: 10.1161/CIRCRESAHA.121.320680.
  • Wang J, Ciampa G, Zheng D, Shi Q, Chen B, Abel ED, Peng T, Hall DD, Song LS. (2021) Calpain-2 specifically cleaves Junctophilin-2 at the same site as Calpain-1 but with less efficacy.  Biochem J. 15;478(19):3539-3553. PMID: 34524407 PMCID: PMC8589432 doi: 10.1042/BCJ20210629.
  • Wang J, Hall DD, Song LS. Nexilin is a New Player for Shaping T-Tubules in Cardiomyocytes. (2020). Circ Heart Fail. 13(7):e007196. PMID: 32635767 PMCID: PMC7375922 .doi: 10.1161 (Invited Editorial). 
  • Wang Y, Li C, Shi L, Chen X, Cui C, Huang J, Chen B,  Hall DD, Pan Z, Lu M, Hong J, Song LS* (lead contact), Zhao S*. Integrin β1D Deficiency-Mediated RyR2 Dysfunction Contributes to Catecholamine-Sensitive Ventricular Tachycardia in Arrhythmogenic Right Ventricular Cardiomyopathy. Circulation. 2020 May 5;141(18):1477-1493. PMID: 32122157 PMCID: PMC7200284. doi: 10.1161/CIRCULATIONAHA.119.043504. Epub 2020 Mar 3.
  • Zheng, D., Su, Z., Zhang, Y., Ni, R., Fan, G. C., Robbins, J., Song, L. S., Li, J. & Peng, T. (2019). Calpain-2 promotes MKP-1 expression protecting cardiomyocytes in both in vitro and in vivo mouse models of doxorubicin-induced cardiotoxicity. Archives of toxicology 93 (4) 1051-1065. DOI: 10.1007/s00204-019-02405-w. PMID: 30810770.
  • Cao, T., Fan, S., Zheng, D., Wang, G., Yu, Y., Chen, R., Song, L. S., Fan, G. C., Zhang, Z. & Peng, T. (2019). Increased calpain-1 in mitochondria induces dilated heart failure in mice: role of mitochondrial superoxide anion. Basic research in cardiology 114 (3) 17. DOI: 10.1007/s00395-019-0726-1. PMID: 30874894.
  • Guo, A., Wang, Y., Chen, B., Wang, Y., Yuan, J., Zhang, L., Hall, D., Wu, J., Shi, Y., Zhu, Q., Chen, C., Thiel, W. H., Zhan, X., Weiss, R. M., Zhan, F., Musselman, C. A., Pufall, M., Zhu, W., Au, K. F., Hong, J., Anderson, M. E., Grueter, C. E. & Song, L. S. (2018). E-C coupling structural protein junctophilin-2 encodes a stress-adaptive transcription regulator. Science (New York, N.Y.) 362 (6421). DOI: 10.1126/science.aan3303. PMID: 30409805. PMCID: PMC6336677.
  • Wang, Y., Chen, B., Huang, C. K., Guo, A., Wu, J., Zhang, X., Chen, R., Chen, C., Kutschke, W., Weiss, R. M., Boudreau, R. L., Margulies, K. B., Hong, J. & Song, L. S. (2018). Targeting Calpain for Heart Failure Therapy: Implications From Multiple Murine Models. JACC. Basic to translational science 3 (4) 503-517. DOI: 10.1016/j.jacbts.2018.05.004. PMID: 30175274. PMCID: PMC6115647.
  • Yan, J., Thomson, J. K., Zhao, W., Gao, X., Huang, F., Chen, B., Liang, Q., Song, L. S., Fill, M. & Ai, X. (2018). Role of Stress Kinase JNK in Binge Alcohol-Evoked Atrial Arrhythmia. Journal of the American College of Cardiology 71 (13) 1459-1470. DOI: 10.1016/j.jacc.2018.01.060. PMID: 29598867. PMCID: PMC5903584.
  • Yan, J., Zhao, W., Thomson, J. K., Gao, X., DeMarco, D. M., Carrillo, E., Chen, B., Wu, X., Ginsburg, K. S., Bakhos, M., Bers, D. M., Anderson, M. E., Song, L. S., Fill, M. & Ai, X. (2018). Stress Signaling JNK2 Crosstalk With CaMKII Underlies Enhanced Atrial Arrhythmogenesis. Circulation research 122 (6) 821-835. DOI: 10.1161/CIRCRESAHA.117.312536. PMID: 29352041. PMCID: PMC5924593.