My laboratory studies the role of chemokines on cardiac myocyte biology. We focus on cardiac physiology in both in vitro and in vivo models of heart failure targeting specific signaling pathways. We have demonstrated that chemokines, once thought to act only on inflammatory cells, can elicit biological responses from cardiac myocytes. This line of research is unique in bridging the areas of immunology (i.e. chemokines) and cardiovascular biology. Our focus is particularly on the CXCR4-CXCL12 regulation and signaling pathways in cardiac myocytes. The CXCR4-CXCL12 regulation and signaling pathways have been extensively studied in developmental processes, stem cell biology and in metastatic disease, focusing primarily on cells with a migratory phenotype. There is little known about CXCR4 signaling in cardiac myocytes. Our studies suggest that under conditions of stress, the paracrine and/or autocrine activation of CXCR4 by its ligand may trigger intracellular signaling pathways which may exacerbate contractile dysfunction. We have demonstrated a clear interaction between CXCR4 and Beta-2 adrenergic receptor and that CXCR4 activation can interfere with Beta adrenergic receptor downstream signaling. In the light of Beta adrenergic importance in progression of heart failure, we have set to examine the mechanistic role of CXCL12-CXCR4 in the pathophysiology of heart disease.
Sima T. Tarzami, PhD
Assistant Professor of Medicine
Cardiovascular Research Center