Project title: Understanding the roles of miR-1s in regulating heart development Project Summary: Congenital heart defects (CHD) are the most common birth defects in humans, resulting in significant mortality and morbidity. The overall goal of this project is to investigate the role of microRNA (miRNA) mediated gene regulation, in heart development. miRNAs are recently identified small RNAs that bind through a poorly understood mechanism to the 34-UTRs of their target mRNAs, inducing mRNA cleavage. The PI previously described two muscle-specific miRNAs, miR-1-1 and miR-1-2. Both miR-1s are highly enriched in the cardiac conduction system (CCS) during cardiogenesis and in adulthood. Deletion of miR-1-2 causes partial embryonic lethality. miR-1-2 null survivors develop cardiac conduction defects but are without obvious cardiac structural abnormalities. Overexpression of miR-1-2 at postnatal stages causes AV block of various degree and sinus bradycardia. The PI hypothesizes that the proper function of each component of the CCS requires a precise dosage of miR-1. The PI proposes three specific aims to test this hypothesis: 1) To determine the role of miR-1s in regulating specification and proliferation of the CCS;2) To determine how different dosages of miR-1 regulate proper function of each component of the CCS;3) To identify the molecular mechanism by which miR-1s regulate cardiac development. The proposed studies may uncover new fundamental mechanisms of heart disease. Insights from the studies will facilitate steps towards understanding of functions of numerous miRNAs in human diseases.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02HL103597-04
Application #
8677954
Study Section
Special Emphasis Panel (ZHL1-CSR-K (F1))
Program Officer
Wang, Wayne C
Project Start
2011-06-16
Project End
2016-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
4
Fiscal Year
2014
Total Cost
$102,465
Indirect Cost
$7,590
Name
Icahn School of Medicine at Mount Sinai
Department
Genetics
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Wei, Yusheng; Peng, Siwu; Wu, Meng et al. (2014) Multifaceted roles of miR-1s in repressing the fetal gene program in the heart. Cell Res 24:278-92
Wu, Meng; Peng, Siwu; Zhao, Yong (2014) Inducible gene deletion in the entire cardiac conduction system using Hcn4-CreERT2 BAC transgenic mice. Genesis 52:134-40