Chuanfu Li, M.D., M.S.
Innate Immunity in Myocardial Ischemia/reperfusion Injury
Our research focuses on understanding the role in innate immunity in myocardial ischemia/reperfusion (I/R) injury. A growing body of evidence suggests that inflammatory pathways initiated by the innate immune system are involved in the pathophysiology of myocardial I/R injury and congestive heart failure. However, the mechanisms by which these innate immune pathways participate in myocardial disease have not been fully elucidated. We are interested in the role of Toll-like receptor (TLR) mediated signaling pathways in myocardial ischemia/reperfusion injury. Toll receptors are an ancient and evolutionarily conserved family of signal transducing molecules which are critical for the induction of innate imunity. Nuclear factor KappaB (NFkB) is an important downstream signaling pathway for TLRs. We have reported that NFkB activation is increased in the heart following I/R. We have also observed that modulation of TLR signaling pathways was induce cardioprotection in I/R. Our long-term goals are to elucidate the immunoregulatory and pro-inflammatory signaling mechanisms associated with myocardial I/R injury.
Our research also focuses on understanding the role of TLR mediated NFkB activation signaling pathway in the development of cardiac hypertrophy. We have demonstrated that nuclear factor kappaB (NFkB) activation is required for cardiac hypertrophy and inhibiting NFkB activation attenuates the development of cardiac hypertrophy in vivo. NFkB is a transcription factor in the downstream of Toll-like receptor (TLR) mediated signaling pathways. We suspect that TLRs might contribute to the development of cardiac hypertrophy. Our long-term goals are to elucidate the mechanisms of the development of cardiac hypertrophy and to develop effective approaches to prevent hypertrophy.