David J. Lefer, Ph.D.

Dr. Lefer has been working in the fields of myocardial protection and coronary physiology for over 20 years and have made important contributions to these fields.  Dr. Lefer’s laboratory was among the first to demonstrate the profound loss of endothelial cell derived nitric oxide (NO) from the coronary circulation following coronary artery occlusion and reperfusion.  A series of subsequent studies in both small and large animal models clearly demonstrated that oxidative stress occurring within the first few minutes of reperfusion significantly impaired NO generation by coronary endothelial nitric oxide synthase (eNOS).  Dr. Lefer’s laboratory was the first to report on the potent cardioprotective actions of NO in the setting of acute myocardial infarction and congestive heart failure in both small and large animal models.  Dr. Lefer has investigated nitrite-based therapies in a number of models of chronic tissue ischemia and ischemia-reperfusion injury. Nitrite has emerged as a safe and efficacious therapy to augment endogenous nitric oxide levels and attenuate the severity of various forms of cardiovascular disease.  Several nitrite therapies are currently in clinical trials in the United States and Europe.  In 2005, Dr. Lefer’s laboratory initiated investigations of the potential cytoprotective actions of a second gaseous signaling molecule, hydrogen sulfide (H2S).  Work performed in Dr. Lefer’s laboratory was among the first to demonstrate the potent protective actions of H2S in acute myocardial infarction and heart failure model systems.  Dr. Lefer’s research investigations have determined that H2S possesses a physiological profile that is very similar to nitric oxide and protects cells via a number of overlapping mechanisms including: attenuation of oxidative stress and apoptosis, mitochondrial protection, and upregulation of pro-survival signaling proteins and pathways.