Localized Control of cAMP Signaling and Novel Therapeutic Approaches for Heart Failure

European Coordinator:
  • Rodolphe FISCHMEISTER, INSERM/Université Paris-Sud, Châtenay-Malabry (France)
North American Coordinator:
  • John SCOTT, University of Washington, Seattle/Howard Hughes Medical Institute (USA)
  • George BAILLIE, University of Glasgow (UK)
  • Michael BRISTOW, University of Colorado, Denver (USA)
  • Marco CONTI, Stanford University, Palo Alto (USA)
  • Emilio HIRSCH, University of Torino (Italy)
  • Miles HOUSLAY, University of Glasgow (UK)
  • Joseph A. BEAVO, University of Washington, Seattle (USA)
  • Brian K. KOBILKA, Stanford University, Palo Alto (USA)
  • Matthew MOVSESIAN, University of Utah (USA)
  • Manuela ZACCOLO, University of Glasgow (UK)

Cyclic AMP (cAMP) is critical to the function of heart cells.  It can be generated in the heart in response to hormones and other signals in the blood, which bind to specific receptors on the heart cell.  Within the heart cell cAMP helps to regulate essential functions such as the flow of calcium, the contraction of the cell (which allows the heart to beat), and the production of important proteins.  Now researchers have discovered that the role of cAMP in the cell can differ depending upon which signal activated it, and upon where in the cell the cAMP is generated.  Network investigators have proposed that cAMP and its various regulatory enzymes are compartmentalized within the cell, that is, are located in distinct spatial regions within the cell.  This finding helps to explain why treatments for heart failure which rely upon the modulation of cAMP often seem to have paradoxical effects: the generation of cAMP will produce different results in different parts of the cell.  The overall goal of the network research program is to be able to isolate the cAMP processes in different parts of the cell, and eventually to develop treatments which could target cAMP related processes at the subcellular level.