Projects and Grants
Main areas of interest
- To define the role of the cardiac myocyte (CM) CXCL12-CXCR4 axis following myocardial injury. Most notably, we found that CXCL12-CXCR4 activation of CM 1) blunts the activity of the major neurotransmitter response system, the β-adrenergic receptor (βAR) and 2) induces apoptosis. Both CXCL12 and CXCR4 expression are significantly up-regulated following MI, and ectopic expression of CXCR4 can increase myocardial infarct size and impair cardiac pump function. CXCR4 over-expression is associated with enhanced production of apoptotic cytokines such as TNF-α production and, indeed, activation of cell death/apoptotic pathways.
- To assess the effect of CXCR4 and its ligand CXCL12 on L type Ca channels activity and heart function. We have recently identified a clear interaction between CXCR4 and Beta-2 adrenergic receptor and that CXCR4 activation can interfere with Beta-2 adrenergic receptor downstream signaling. We will identify the mechanisms underlying CXCR4 effects on βAR-induced L-VDCC internalization/desensitization and determine the functional significance of this interaction on calcium current and myocytes inotropic response.
- To assess the role of the CXCR4 on isoproterenol-induced cardiac hypertrophy and deciphering the negative modulatory role of CXCR4 and its contribution to Beta-2 adrenergic-mediated cardiac dysfunction.
- CXCR4 modulation of L type Ca channels (PI: Sima Tarzami)
Agency: AHA/Founders Affiliate (Scientist Development Grant) SDG-735576T
Extension: Project is extended one more year (06/30/10-06/30/11).
- SDF-1/CXCR4 activation prevents isoproterenol-induced hypertrophy in cardiac myocyte (PI: Sima Tarzami)
Agency: AHA/Founders Affiliate (Grant-in-Aid) 10GRNT4180006
- Chemokine receptor-4 activation regulates Beta-2 adrenergic-mediated calcium channel internalization/desensitization and its subsequent activity (PI: Sima Tarzami)
Agency: NIH/NHLBI 1K02HL102163-01