Heart disease is a major cause of morbidity and mortality in developed nations. Although tremendous progress has been made in the treatment of heart disease, there is currently no cure: the cells that compose the heart are irreplaceable, having terminally differentiated late in development. Identifying the molecular mechanisms that specify cardiac cell fates may allow the development of regenerate therapies for damaged, diseased or malformed heart tissue. Cardiogenic transcription factors regulate constellations of downstream genes in order to effect cardiac cell fates. In particular, the two transcriptional activators MEF2C and dHAND are both required for the development of the right ventricular chamber in mice. Identifying the genes that are direct targets of MEF2C and dHAND will show how cardiac cell fates are effected and may describe deeper motifs on the nature of cell fate in general. Specifically, this project will use microarray analyses to identify genes that are down regulated in MEF2C and dHAND mutant hearts. Cellular cardiogenesis assays will then be used to identify the subset of downstream genes that are required for cardiac cell fates. Finally, the roles of these cardiogenic effector genes will be studied in vivo, using loss-of-function and gain-of-function mutant alleles and genetic interaction tests.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL070501-02
Application #
6626199
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Commarato, Michael
Project Start
2002-06-01
Project End
2005-05-31
Budget Start
2003-06-01
Budget End
2004-05-31
Support Year
2
Fiscal Year
2003
Total Cost
$46,420
Indirect Cost
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