Email : Christine.Chaponnier@ unige.ch
Tel: + 41 22 3795766 / Fax: +41 22 3795746
Addresses

Research areas: The role of amino-terminal sequences in actin isoform function

alpha-Smooth Muscle Actin (alpha-SMA) is transiently or permanently induced (i.e. de novo expression) in fibroblastic cells (myofibroblasts) during fibrocontractile phenomena such as wound healing, lung and hepatic fibrosis. alpha-SMA differs from the other actin isoforms mainly at its N-terminal tetrapeptide sequence, AcEEED. We have previously shown that this unique sequence is important for alpha-SMA polymerization. We now have strong evidence that this sequence is essential for alpha-SMA increased myofibroblast contractile activity. We have observed for the first time that the peptide AcEEED, which can be efficiently delivered intracellularly when linked to a cell penetrating peptide (pAntp), causes a dramatic decrease in contractile activity of myofibroblasts both in vitro and in vivo. We will investigate  the mechanism by which AcEEED inhibits myofibroblast contraction. These studies may lead to specific and efficient mechanisms for therapeutic intervention. We will broaden our research to the other actin isoforms. We presently have produced three monoclonal antibodies (against the N-terminal sequence of alpha-skeletal, alpha-cardiac and beta-cytoplasmic actins), and are in the process for the two last actins, gamma-SM and beta-cytoplasmic. We believe that the localization of specific actin isoforms during physiological and pathological phenomena, and the peptide cell delivery technology will be critical to understanding isotype function.