Elizabeth Murphy, Ph.D.
Elizabeth Murphy received her B.A. in 1974 and her Ph.D. in biochemistry in 1980 from the University of Pennsylvania. From 1980 to 1983, she was a postdoctoral fellow and then an assistant research professor at Duke University Medical Center (DUMC). Before joining the NHLBI in 2006 as the head of the Cardiac Physiology Section, she was the head of the Cell Biology Group at the National Institute of Environmental Health Sciences. She was an adjunct professor in the Division of Physiology, Department of Cell Biology at DUMC between 1984 and 2009. She became a Fellow of the American Heart Association in 2001 and a Fellow of the International Society for Heart Research in 2007; she received the NHLBI Award for Outstanding Mentorship in 2011. Dr. Murphy has authored or co-authored more than 200 papers and reviews. She is senior guest editor for Circulation, a consulting editor for Circulation Research, and associate editor for the Journal of Molecular and Cellular Cardiology. Dr. Murphy is a member of the American Heart Association-Council of Basic Cardiovascular Research, American Physiological Society, and International Society for Heart Research.
- Elizabeth Murphy, Ph.D.
Cardiovascular disease diseases are often characterized by inappropriate cardiomyocyte death. Adult cardiomyocytes are post-mitotic cells which undergo very limited cell division. Thus, cardiomyocyte death as occurs during myocardial infarction has very detrimental consequences for the heart. In spite of considerable research effort, the mechanisms responsible for cardiomyocyte death are poorly understood. This lack of mechanistic understanding is a major contributor to the failure to translate cardioprotective drugs to the clinic. The overall goal of the research effort from the Murphy laboratory is to use a multipronged, interactive approach to elucidate the mechanisms responsible for cardiomyocyte death and to define cardioprotective strategies. Mitochondria are well established as bioenergetic hubs for generating ATP, but have also been shown to regulate cell death pathways. Indeed many of the same signals used to regulate metabolism and ATP production, such as calcium and reactive oxygen species (ROS), are also key regulators of mitochondrial cell death pathways. It is widely hypothesized that an increase in calcium and ROS activate a large conductance channel in the inner mitochondrial membrane known as the permeability transition pore (PTP) and that opening of this pore leads to necroptosis, a regulated form of necrotic cell death. Strategies to reduce PTP opening either by inhibition PTP or inhibiting the rise in mitochondrial calcium or ROS which activate PTP have been proposed. A major limitation of inhibiting the PTP is the lack of knowledge about the identity of the protein(s) that form the PTP and details of how PTP is activated by calcium, ROS and cyclophilin D (CypD), a matrix protein that has been shown to activate PTP. Sex differences in cardioprotection have been described and another goal of my research is to elucidate the mechanisms involved. A better understanding of these mechanisms will not only impact treatment of females, but will likely provide new insights into the mechanisms of cardioprotection. Project 1, illustrated in orange in Figure 1, is focused on developing a better understanding of the mechanisms responsible for cardiomyocyte death. This project elucidates the mechanisms that regulate the PTP including understanding the mechanism by which CypD activates PTP. The project also examines the role of nitric oxide (NO) signaling and S-nitro(sy)lation (SNO), an NO dependent post-translational modification (PTM), in regulating PTP and other mechanisms of cardioprotection. Project 2 (in blue) focuses on the regulation of mitochondrial calcium a key activator of the PTP and cell death. Sex differences in cardiovascular disease are known and Project 3 will focus on sex differences in cardioprotection and mechanisms of protection in females. Project 4 takes a somewhat different approach; it focuses on the role of proline hydroxylation in regulating cardiovascular disease. Proline hydroxylation is mediated by enzymes that are regulated by oxygen and mitochondrial metabolites which are altered during disease. Altogether these studies integrate multiple cutting edge technologies to push back the frontiers of our understanding of mechanisms of cardiomyocyte death in cardiovascular disease.