Cardiovascular disease (CVD) is arguably the greatest non-infectious health care problem ever to afflict mankind and lung disease is not far behind. Stem/progenitor cells hold great promise to replace cardiomyocytes after myocardial infarction (Ml) or alveoli after lung injury, but there is little agreement on how best to differentiate these cells and ensure in vivo functionality. Our approach to cardiac and lung regeneration/repair is innovative and based on solid preliminary findings. Indeed, collectively we have been working in this field and preparing for participation in this Consortium for more than two decades. We are committed to exploring the mechanistic underpinnings of the native myocardial repair process, discovering natural barriers that prevent effective repair, and devising synthetic small molecule and miR-based pharmaco-therapies and strategies to overcome these barriers. The overall goal of our group will be to combine the power of miRs, small molecules and native stem/progenitor cells to dissect fundamental mechanisms controlling cell fate, and to exploit these new discoveries to ultimately develop therapeutics. We propose three specific aims that will provide new starting points for therapeutic RNA and drug development, while expanding the mechanistic science of cardiac and lung regeneration and repair.
The aims are:
Aim 1. Define cell fate mechanisms in the native microenvironment;
Aim 2. Develop a mechanistic signaling map of how pathophysiological stress/injury promotes structural and functional repair;
Aim 3. Collaborate Consortium-wide to develop education programs that can steer iPS cells towards desired fates and enhance their function in vivo. To accomplish these aims, we have functionally merged two synergistic and interactive progenitor cell biology groups at Harvard and UT Southwestern, and we have already generated promising preliminary data through team science. As a member of NHLBI Progenitor Cell Biology Consortium, our proposed Hub will make substantial and important contributions to advancing this new frontier of cardiovascular and pulmonary regenerative medicine.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL100401-05
Application #
8496864
Study Section
Special Emphasis Panel (ZHL1-CSR-J (S1))
Program Officer
Tolunay, Eser
Project Start
2009-09-30
Project End
2016-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
5
Fiscal Year
2013
Total Cost
$1,138,045
Indirect Cost
$361,441
Name
University of Texas Sw Medical Center Dallas
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Lee, Ji-Hoon; Bassel-Duby, Rhonda; Olson, Eric N (2014) Heart- and muscle-derived signaling system dependent on MED13 and Wingless controls obesity in Drosophila. Proc Natl Acad Sci U S A 111:9491-6
Porrello, Enzo R; Olson, Eric N (2014) A neonatal blueprint for cardiac regeneration. Stem Cell Res 13:556-70
Hu, Yong; Pu, William T (2014) Hippo activation in arrhythmogenic cardiomyopathy. Circ Res 114:402-5
Wang, Gang; McCain, Megan L; Yang, Luhan et al. (2014) Modeling the mitochondrial cardiomyopathy of Barth syndrome with induced pluripotent stem cell and heart-on-chip technologies. Nat Med 20:616-23
Wang, Zhao V; Li, Dan L; Hill, Joseph A (2014) Heart failure and loss of metabolic control. J Cardiovasc Pharmacol 63:302-13
Mahmoud, Ahmed I; Porrello, Enzo R; Kimura, Wataru et al. (2014) Surgical models for cardiac regeneration in neonatal mice. Nat Protoc 9:305-11
Nam, Young-Jae; Lubczyk, Christina; Bhakta, Minoti et al. (2014) Induction of diverse cardiac cell types by reprogramming fibroblasts with cardiac transcription factors. Development 141:4267-78
Lin, Zhiqiang; von Gise, Alexander; Zhou, Pingzhu et al. (2014) Cardiac-specific YAP activation improves cardiac function and survival in an experimental murine MI model. Circ Res 115:354-63
Schober, Andreas; Nazari-Jahantigh, Maliheh; Wei, Yuanyuan et al. (2014) MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by suppressing Dlk1. Nat Med 20:368-76
Munshi, Nikhil V; Olson, Eric N (2014) Translational medicine. Improving cardiac rhythm with a biological pacemaker. Science 345:268-9

Showing the most recent 10 out of 64 publications