Elizabeth Murphy received her B.A. in 1974 and her Ph.D. in biochemistry/biophysics in 1980 from the University of Pennsylvania, where she was also a research fellow. From 1980 to 1983, she was a postdoctoral fellow and 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 125 papers and more than 45 invited chapters 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.
In the heart, interruption of the blood supply can result in cardiac cell death and irreversible muscle damage. Dr. Murphy’s laboratory studies the molecular mechanisms involved in cardiac cell death, as well as the mechanisms that protect the heart against damage. The knowledge gained from these studies may help identify novel therapies to reduce cardiac injury during ischemia and reperfusion.
Dr. Murphy’s work has revealed that many cardioprotective agents trigger the activation of PI3-kinase, which leads to the phosphorylation of a number of downstream signaling molecules such as AKT, protein kinase C (PKC), glycogen synthase kinase-3β (GSK-3β), nitric oxide synthase (NOS), ERK MAP-kinase, and the mitochondrial KATP channel. Observing that several of these signaling proteins and kinases are localized to the mitochondria, Dr. Murphy has turned her attention to the hypothesis that cardioprotective agents induce posttranslational modifications of mitochondrial proteins that reduce activation of the mitochondrial permeability transition (MPT) during ischemia and reperfusion. The exact identity of the proteins that comprise the MPT pore is still unknown, but activating the MPT has been reported to lead to a loss of mitochondrial function and subsequent cell death through either apoptosis or necrosis.
To learn more about the MPT and its regulation, Dr. Murphy and her team study two complementary aspects of this pore complex. First, they are identifying the mitochondrial components that might be involved in forming the MPT pore, such as mitochondrial transporters, proteins involved in electron transport, and fission/fusion proteins.
They also look for the post-translational modifications, protein-protein interactions , and physiological factors such as reactive oxygen species (ROS) or calcium that might regulate the MPT. Dr. Murphy’s group has already identified a number of changes in mitochondrial protein phosphorylation during cardioprotection. They have also found that cardioprotection results in an activation of endothelial nitric oxide synthase (eNOS), which mediates S-nitrosylation, a protein modification related to nitric oxide signaling. Her laboratory has used a number of novel proteomic methods to identify S-nitrosylated proteins and is currently studying their role in cardioprotection.
As part of her overall interest in cardioprotection, Dr. Murphy has a specific interest understanding the natural cardioprotection that exists among pre-menopausal females. She and her colleagues have determined that this cardioprotection in females is mediated by the beta-estrogen receptor and that protection by beta-estrogen involves S-nitrosylation. For example, they have shown that S-nitrosylation of the L-type Ca2+ channel in females reduces Ca2+ entry into the heart, thereby reducing the risk of calcium overload which can trigger cell death. They also find that estrogen can mediate PI3-kinase protection via activation of a novel G protein coupled receptor, GPR30 (also known as GPER). Interestingly, females have altered phosphorlyation patterns in response to cardioprotection, such as increased phosphorylation of the mitochondrial proteins aldehyde dehydrogenase and alpha ketoglutarate dehydrogenase. Phosphorylation of these proteins results in less generation of ROS and/or improved handling of ROS. Her laboratory is currently examining whether selective estrogen receptor modulators (SERMs), can mediate cardioprotection in a similar fashion to endogenous estrogen, opening up a possible therapeutic avenue to reduce heart attack damage in women.