Skip to main content
European Commission logo print header

Cardiac Death and Regeneration

Ziel

Cardiac muscle death, unmatched by muscle cell creation, is the hallmark of acute myocardial infarction and chronic cardiomyopathies. The notion of heart failure as a muscle-cell deficiency disease has driven interest worldwide in ways to increase heart muscle cell number, by over-riding cell cycle constraints, suppressing cell death, or, most directly, cell grafting. Using stem cell antigen-1, we previously identified telomerase-expressing cells in adult mouse myocardium, which have salutary properties for bona fide cardiac regeneration. Here, we seek to address systematically the mechanisms for long-term self-renewal in Sca-1+ adult cardiac progenitor cells and in the smaller side population fraction, which is clonogenic and expresses telomerase at even higher levels. Specifically, we propose to study the roles of telomerase and of the telomere-capping protein, TRF2. Aim 1, Determine the properties of adult cardiac progenitor cells in mice that lack the RNA component of telomerase (TERC). Aim 2, Determine the properties of adult cardiac progenitor cells in mice that lack the catalytic component (TERT). To distinguish between effects of these two gene products themselves versus those that depend on cumulative telomere dysfunction, G2- and G5-null mice will be compared. Aim 3, Determine the properties of adult cardiac muscle and adult cardiac progenitor cells that lack the telomere-capping protein TRF2. Aim 4, Test the prediction that forced expression of TERT and TRF2 can augment cardiac muscle engraftment in vivo and enhance the clonal derivation of adult cardiac progenitor cells in vitro, without adversely affecting the cells differentiation potential. Work proposed in Aims 1-3 would provide indispensable fundamental information about the function of endogenous telomerase in adult cardiac progenitor cells. Conversely, work in Aim 4 would test potential therapeutic implications of telomerase and a telomere-capping protein with this auspicious population.

Aufforderung zur Vorschlagseinreichung

ERC-2008-AdG
Andere Projekte für diesen Aufruf anzeigen

Gastgebende Einrichtung

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
EU-Beitrag
€ 2 497 576,00
Adresse
SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
SW7 2AZ LONDON
Vereinigtes Königreich

Auf der Karte ansehen

Region
London Inner London — West Westminster
Aktivitätstyp
Higher or Secondary Education Establishments
Hauptforscher
Michael David Schneider (Prof.)
Kontakt Verwaltung
Tatjana Palalic (Ms.)
Links
Gesamtkosten
Keine Daten

Begünstigte (1)