hES-CardioProject reference: 276186
Funded under :
Cardiac myosin light chain kinase function in human pluripotent stem cell derived cardiomyocytes
Total cost:EUR 268 824,8
EU contribution:EUR 268 824,8
Coordinated in:United Kingdom
Topic(s):FP7-PEOPLE-2010-IOF - Marie Curie Action: "International Outgoing Fellowships for Career Development"
Call for proposal:FP7-PEOPLE-2010-IOFSee other projects for this call
Funding scheme:MC-IOF - International Outgoing Fellowships (IOF)
The main hurdle to the effective use of stem cell derived cardiomyocytes (hESC-CMs and hIPSC-CMs) in drug toxicology screening and transplantation therapy is their embryonic nature. It is recognised that hESC-CM and hIPSC-CM are immature and undergo limited maturation in the laboratory. This creates problems as the cells may not display appropriate responses to target drugs in toxicology screening and may not be suitable for transplantation into the damaged heart. The research outlined in this proposal will begin to address these issues.
The aim of my proposal is to study the function and regulation of the recently discovered cardiac myosin light chain kinase (MLCK) and its downstream targets, regulatory myosin light chain (MLC) proteins. Evidence suggests that cardiac MLCK is responsible for modulating cardiomyocyte contractility. In studying the function of cardiac MLCK I aim to generate hESC-CM and hIPSC-CM with an increased structural maturity, which will be more suitable for drug toxicology screening.
Importantly, the study of cardiac MLCK also has clinical relevance. Expression of cardiac MLCK is downregulated in the hearts of rats that suffered induced myocardial infarction, and when used to treat these animals, upregulation of the gene can improve cardiac output. Investigation of cardiac MLCK function in human cardiomyocytes in this proposal may provide insights into a potential role for cardiac MLCK in the treatment of heart attack patients.
Finally, the proposed research will also highlight the potential of hESC-CM and hIPSC-CM as models to study the basic biology of the human heart.
EU contribution: EUR 268 824,8
TRINITY LANE THE OLD SCHOOLS
CB2 1TN CAMBRIDGE
Tel.: +44 1223 333543
NG7 2RD NOTTINGHAM
Tel.: +44 115 9515679
Fax: +44 115 9513633