Regulation of intercellular communication in the heart, gene expression during macrophage activation
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Role of Connexin43 (Cx43) in the immune System
We have developed a model system to study the role of the gap junction protein Cx43 in the immune system of mice. There are many reports that suggest that Cx43 is a critical for a variety of immune functions. We are particularly interested in the role of connexins in the function of macrophages in inflammation.
Acidification based gating of the Cardiac Gap Junction (with M. Delmar)
This study has defined the structures of the cardiac gap junction protein (Connexin 43, Cx43) that are involved in the pH-based gating of this channel. We have created a series of compounds that modulate the gating of Cx43 and help maintain the function of the channel in pathologic conditions. These compounds may have efficacy in the prevention of cardiac arrhythmias subsequent to ischemic heart disease.
The effect of inflammatory heart disease on the cardiac gap junction.
We have initiated a study to determine the effect of inflammatory processes on cardiac junctional proteins. We are using both viral infections and the induction of autoimmune disease to study the mechanisms by which the cardiac electrical conduction if altered during inflammation.
Nguyen TD, Taffet SM. A model system to study Connexin 43 in the immune system. Mol Immunol. 46(15):2938-46 (2009).
Lewandowski, R., Procida, K., Vaidyanathan, R., Coombs, W., Jalife, J., Nielsen, M.S., Taffet, S.M., and Delmar, M. RXP-E: a connexin43-binding peptide that prevents action potential propagation block. Circulation Res. 103:519-26. (2008).
Shibayama, J., Lewandowski, R., Kieken, F., Coombs, W., Shah, S., Sorgen, P.L., Taffet, S.M.,* and Delmar, M*. Identification of a novel peptide that interferes with the chemical regulation of connexin43. Circulation Research: 98:1365-72 (2006)