Investigator,The Feinstein Institute for Medical Research
Professor, The Elmezzi Graduate School of Molecular Medicine
Professor, The Hofstra-NSLIJ School of Medicine
Phone: (516) 562-1309
Dr. Powell received his BSc in Pharmacy from the Philadelphia College of Pharmacy & Science in 1976, and his PhD in Pharmacology from the Medical College of Pennsylvania (now Drexel University School of Medicine) in 1983. He completed post-doctoral studies focusing on various aspects of free radical induced tissue injury at the Oklahoma Medical Research Foundation in Oklahoma City and the Hebrew University Hadassah School of Medicine in Jerusalem, Israel. He has been associated with the Research Institute since 1987 with a hiatus of three years from 1998-2001.
Dr. Powell’s early studies at the Institute focused on the role of free radicals in heart injury and preventative measures and during this time obtained a patent on the use of a zinc complex to prevent injury during heart surgery. In the last 12 years, his research has shifted somewhat to focus in on the role of the ubiquitin proteasome system in maintaining normal cellular function. The ubiquitin proteasome system is the major pathway for removing cellular proteins and is responsible for a process known as “protein quality control”. When the cell synthesizes a protein, it must be properly assembled and folded, otherwise it can be toxic to the cell. When a protein is not assembled or folded properly it is removed by the ubiquitin proteasome system. Other proteins, which may control cell functions, are removed by the ubiquitin proteasome system as a means of stopping their biologic activity. Thus by removing proteins, the ubiquitin proteasome system actually regulates many cell functions in a process known as “regulation by destruction”. Function of this system has been shown to be altered in many disease states.
The key findings of Dr. Powell’s ongoing studies is that during a heart attack the ubiquitin proteasome system may lose activity, and that during early heart failure activity may actually increase, yet in end stage heart failure leading to transplantation, function of this system is severely diminished. More recent studies in collaboration with other Institute Investigators have indicated that function of the ubiquitin proteasome system is altered in septic shock and pulmonary hypertension.
Dr. Powell has published over 60 articles and has been funded by the National Institutes of Health and the American Heart Association. He has received several honors and is currently a Fellow of the American Heart Association. He is active in intramural graduate education both in the Elmezzi Graduate School of Molecular Medicine and the new Hofstra-NSLIJ School of Medicine and is the only Institute faculty to hold an appointment in the Department of Science Education. In addition, he is active in extramural undergraduate education having taught at a local university for over 15 years.
Dr. Powell is involved in cardiac metabolism research at the Center for Heart & Lung Research. The Laboratory of Cardiac Metabolism examines the role of the ubiquitin proteasome system in cellular function and malfunction. Function of the ubiquitin proteasome system has been shown to be altered in many pathologic states. In the lab, Dr. Powell conducts ongoing studies with several collaborators that examine altered function of the ubiquitin proteasome system in several diseases.
The lab’s studies have established that the ubiquitin proteasome system can malfunction during a heart attack. When this happens proteins that are normally removed by this system accumulate. Many of these proteins are either highly reactive or damaged and their accumulation is toxic to the cell. In studies, with Dr. Xuejun Wang from the University of South Dakota, they have established that increasing the amount of a particular form of the proteasome can help to remove damaged proteins and decrease the injury to heart muscle associated with a heart attack.
In collaborative studies with Dr. Sharlene Day from the University of Michigan, they have established in human hearts that in end stage heart failure, the ubiquitin proteasome system becomes severely dysfunctional. In more recent studies, they are examining the function of the ubiquitin proteasome system in the early stages of heart failure and have observed that activity of a peculiar from of the proteasome that may foster inflammation is actually increased. They are examining means of decreasing this and thus decrease heart injury.
In collaborative studies with Dr. Christine Metz of the Feinstein Institute, they have shown that the same form of the proteasome that fosters inflammation is also increased in sepsis. They have shown that certain drugs that decrease kidney damage during sepsis may work by inhibiting the function of this form of the proteasome.
In collaborative studies with Dr. Edmund Miller of the Feinstein Institute, they are also examining the role of the ubiquitin proteasome system in pulmonary hypertension. Although these studies are still in their infancy the initial studies suggest that the same proteasome that fosters inflammation is also increased in lung from experimental models of pulmonary hypertension
Philadelphia College of Pharmacy & Science, Philadelphia, PA
1971 – 1976
Field of Study: Pharmacy
Medical College of Pennsylvania, Philadelphia, PA
Field of Study: Pharmacology
Oklahoma Medical Research Foundation, Oklahoma City, OK
Field of Study: Oxidative Injury
Johns Hopkins School of Medicine, Baltimore MD
Field of Study: Cardiac oxidative injury
1987 Faculty Fellowship, Hadassah School of Medicine, Hebrew University of Jerusalem
1983-1986 NRSA Postdoctoral Fellow, Oklahoma Medical Research Foundation, Oklahoma City, OK
2000-2003 François Eric Fellow, Heritage Affiliate, American Heart Association
2001 Fellow of the American Heart Association, Basic Science Council
2001-2007 International Editorial Board, Free Radical Biology and Medicine
- Powell, S.R.; Divald, A.” The ubiquitin proteasome system in myocardial ischemia and ischemic preconditioning.” Cardiovascul. Res. 85: 303-311, 2010. (PMCID: PMC2797450)
- Predmore, J.L., Wang, P., Davis, F., Bartolone, S., Westfall, M.V., Dyke, D.B., Pagani, F., Powell, S.R, Day, S.M., “Ubiquitin proteasome dysfunction in human hypertrophic and dilated cardiomyopathies.” Circulation, 121: 997-104, 2010. (PMCID: PMC2857348)
- Divald, A., Kivitys, S., Wang, P., Roberts, B., Hochhauser, E., Teichberg, S., Powell, S.R., “Myocardial ischemic preconditioning preserves proteasome function through diminished oxidation of 19S regulatory subunits.” Circulation Research, 106: 1829-1838, 2010. (PMID:20431057 [PubMed - indexed for MEDLINE])
- Koga, K, Kenessey, A., Powell, S.R., Miller, E.J., Ojamaa, K., “Oxidoreductase function of macrophage migration inhibitory factor provides cardioprotection during ischemia/reperfusion.” Antioxidants Redox Signaling, 14(7): 1191-1201, 2011.
- Li, J, Powell, S.R., Wang, X., “Overexpression of PA28a enhances proteasome function in cardiomyocytes.” FASEB J, 25: 883-893, 2011. (PMCID: PMC3042837)
- Wang, X., Li, J., Zheng, H., Su, H., Powell, S.R., “Proteasome functional insufficiency in cardiac pathogenesis.” Am. J. Physiol. Heart Circ. Physiol., 301(6): H2207-19, 2011. (PMCID: PMC3233812)
- Chatterjee P.K., Yeboah M.M., Dowling O., Xue X., Powell S.R., Al-Abed Y., Metz C.N. “Nicotinic acetylcholine receptor agonists attenuate septic acute kidney injury in mice by suppressing inflammation and proteasome activity.” PLoS One 2012;7(5):e35361.
- Powell, S.R., Herrmann, J., Lerman, A., Patterson, C., Wang, X., , “The Ubiquitin-Proteasome System and Cardiovascular Disease,” Prog. Mol. Biol. Transl. Sci., 109:295-346, 2012.
- Calise, J., Powell, S.R., “The Ubiquitin Proteasome System in myocardial ischemia.” Am. J. Physiol. Heart Circ. Physiol., 2012 (accepted).
- Day, S.M., Divald, A., Jones, R., Powell, S.R., “Impaired assembly and post-translational regulation of 26S Proteasome in human end stage heart failure.” Circulation Heat Failure, 2012 (accepted).