Myocardial infarction or chronic cardiomyopathies can cause irreversible damage to the cardiac tissue. Recent evidence for multipotent cardiovascular stem cells has raised expectations that these cells may be engaged to heal the injured myocardium. However, the biological properties of cardiovascular stem cells are poorly understood, we know little about how disease limits the regenerative potential of stem cells and, we lack pharmaceuticals to guide stem cells toward forming new cardiac tissue. To address these issues, the Vanderbilt University Hub proposes three interacting projects (P1-P3), a Hub Core and a Consortium-wide Bioinformatics Core. PI will focus on the role of adult progenitor cells in normal cardiac homeostasis and after ischemic injury. P2 will explore the regenerative potential of endocardial progenitor cells. Whereas P3 will investigate how the disease environment affects the fate of progenitor cells in the heart. We have designed a pilot study to screen small molecular libraries for compounds that Induce endocardial and myocardial differentiation. Positive hits will be evaluated for effects on cardiac stem cells and myocardial repair. The Hub structure also incorporates a Core for standardized mouse models of myocardial injury and assessment of cardiac histology and function. Finally, we propose a Bioinformatics Core to organize Consortium data into a Stem Cell database to accelerate discovery, strength the connections between Consortium partners and facilitate the dissemination of information to the scientific community and the public. The Vanderbilt Hub will create a dynamic and interactive network of investigators to advance our knowledge about the biology of cardiovascular progenitor cells and their role in cardiac tissue repair. The proposed experiments will lead to novel molecular and cellular tools for the therapy of cardiovascular diseases.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Buxton, Denis B
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Vanderbilt University Medical Center
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Sysa-Shah, Polina; Tocchetti, Carlo G; Gupta, Manveen et al. (2016) Bidirectional cross-regulation between ErbB2 and β-adrenergic signalling pathways. Cardiovasc Res 109:358-73
Favreau-Lessard, Amanda J; Ryzhov, Sergey; Sawyer, Douglas B (2016) Novel Biological Therapies Targeting Heart Failure: Myocardial Rejuvenation. Heart Fail Clin 12:461-71
Sanders, Lehanna N; Schoenhard, John A; Saleh, Mohamed A et al. (2016) BMP Antagonist Gremlin 2 Limits Inflammation After Myocardial Infarction. Circ Res 119:434-49
Wu, Jing; Montaniel, Kim Ramil C; Saleh, Mohamed A et al. (2016) Origin of Matrix-Producing Cells That Contribute to Aortic Fibrosis in Hypertension. Hypertension 67:461-8
Bylund, Jeffery B; Hatzopoulos, Antonis K (2016) Differentiation of Atrial Cardiomyocytes from Pluripotent Stem Cells Using the BMP Antagonist Grem2. J Vis Exp :
Paik, David T; Rai, Meena; Ryzhov, Sergey et al. (2015) Wnt10b Gain-of-Function Improves Cardiac Repair by Arteriole Formation and Attenuation of Fibrosis. Circ Res 117:804-16
Galindo, Cristi L; Kasasbeh, Ehab; Murphy, Abigail et al. (2014) Anti-remodeling and anti-fibrotic effects of the neuregulin-1β glial growth factor 2 in a large animal model of heart failure. J Am Heart Assoc 3:e000773
Fioret, Bryan A; Heimfeld, Jeremy D; Paik, David T et al. (2014) Endothelial cells contribute to generation of adult ventricular myocytes during cardiac homeostasis. Cell Rep 8:229-41
Hao, Jijun; Galindo, Cristi L; Tran, Truc-Linh et al. (2014) Neuregulin-1β induces embryonic stem cell cardiomyogenesis via ErbB3/ErbB2 receptors. Biochem J 458:335-41
Plank, Jennifer L; Suflita, Michael T; Galindo, Cristi L et al. (2014) Transcriptional targets of Foxd3 in murine ES cells. Stem Cell Res 12:233-40

Showing the most recent 10 out of 38 publications