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Research Assistant Professor of Biochemistry and Biophysics
Ph.D. University of Rochester (1987)
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NMR imaging and spectroscopy; Tumor biology; RNA structure determination; anion transport
The lab is involved with a wide variety of collaborations with investigators from throughout the Medical Center. The ongoing projects include mechanistic studies of an anion transport protein, studies of tumor physiology and response of tumors to therapy, development of cold storage methods for transplant organ preservation, and characterization of water diffusion in tissue and the implications for diffusion-weighted MR imaging. While the diverse range of projects encompass applications in oncology, molecular biophysics, radiology, transplant surgery, and winter survival of frogs, they all employ magnetic resonance spectroscopy and/or imaging as an experimental tool.
Studies of the anion transport mechanism of band 3 are carried out with 35Cl nuclear magnetic relaxation experiments and multiple-quantum-filtered NMR spectroscopy which provide measures of chloride ion binding kinetics and dynamics. Structrual aspects of the binding site are probed using a variety of transport inhibitors.
The development and optimization of cancer therapies is aided by monitoring critical aspects of tumor physiology. All tumor therapies must deal with the fact that major portions of many tumors are difficult to treat because of poor blood supply, low oxygen concentrations, and uniquely adapted cellular metabolisms. We have been developing methods to monitor blood flow, intra- and extravascular oxygen concentration, and tissue metabolites. The aim is to develop tools which can aid identification of events following (or during) a treatment protocol, and allow treatment (or pretreatment) conditions to be rationally optimized. Recently we have developed a method to monitor average blood velocities in tumors once every 2-3 minutes, which is an improvement over techniques which require injection of a tracer.
By monitoring the metabolism of hearts that are stored at low temperatures, we have demonstrated how access to oxygen plays a critical role in the eventual viability of the transplanted organ. An organ stored at freezing temperatures consumes far less oxygen than the same organ at room or body temperature. Thus, oxygen can diffuse much farther into the tissue and help maintain normal levels of important metabolites. By continuously mapping the metabolic status in the cold-stored heart, we can assess the effectiveness of different approaches to maintaining tissue oxygen.
In a clearly related process, but entirely different field, we have been studying the physiology of freeze tolerant vertebrates (specifically, wood frogs) under conditions which mimic a winter freeze. The goal is to better understand the adaptations which allow these animals to survive prolonged periods during which 60%-70% of their body fluid is turned to ice.
More recently we have begun work on projects aimed at the characterization of apparent water diffusion in tissue (primarily brain) and the implications for diffusion-weighted MR imaging (DW-MRI). Clinical application of DW-MRI is making substantial contributions in the assessment of stroke damage, yet the details of the water transport events leading to the effects in images are not fully understood. We aim to investigate the possibility that cytoplasmic streaming influences the images, as well as other processes.
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Chen G, Kierzek R, Yildirim I, Krugh TR, Turner DH, Kennedy SD (2007) Stacking Effects on Local Structure in RNA: Changes in the Structure of Tandem GA Pairs when Flanking GC Pairs are Replaced by isoG-isoC Pairs. J Phys Chem B, 111:6718-6727
Tolbert BS, Kennedy SD, Schroeder SJ, Krugh TR, Turner DH (2007) NMR structures of (rGCUGAGGCU)2 and (rGCGGAUGCU)2: probing the structural features that shape the thermodynamic stability of GA pairs. Biochemistry, 46:1511-22
Wong CK, Kennedy SD, Kwok E, Zhong J (2007) Theoretical studies of the effect of the dipolar field in multiple spin-echo sequences with refocusing pulses of finite duration. J Magn Reson, 185:247-58
Shankar N, Kennedy SD, Chen G, Krugh TR, Turner DH (2006) The NMR structure of an internal loop from 23S ribosomal RNA differs from its structure in crystals of 50s ribosomal subunits. Biochemistry, 45:11776-89
Chen G, Kennedy SD, Qiao J, Krugh TR, Turner DH (2006) An alternating sheared AA pair and elements of stability for a single sheared purine-purine pair flanked by sheared GA pairs in RNA. Biochemistry, 45:6889-903
Zheng B, Chen Z, Kennedy SD, Zhong J (2006) iDQC MRI weighted by longitudinal relaxation in the rotating frame. Magn Reson Med, 56:327-33
Chen G, Znosko BM, Kennedy SD, Krugh TR, Turner DH (2005) Solution structure of an RNA internal loop with three consecutive sheared GA pairs. Biochemistry, 44:2845-56
Kennedy SD, Zhong J (2004) Diffusion measurements free of motion artifacts using intermolecular dipole-dipole interactions. Magn Reson Med, 52:1-6
Zhong J, Chen Z, Kennedy SD (2004) Properties and applications of intermolecular dipole-dipole interactions in biomedical NMR. Review invited by Recent Research Developments in Chemical Physics, 5:23-55
Schroeder SJ, Fountain MA, Kennedy SD, Lukavsky PJ, Puglisi JD, Krugh TR, Turner DH (2003) Thermodynamic stability and structural features of the J4/5 loop in a Pneumocystis carinii group I intron. Biochemistry, 42:14184-96
Yan S, Kennedy SD, Koide S (2002) Thermodynamic and kinetic exploration of the energy landscape of Borrelia burgdorferi OspA by native-state hydrogen exchange. J Mol Biol, 323:363-75
Zhong J, Chen Z, Kwok WE, Kennedy SD, You Z (2002) Optimization of blood oxygen level-dependent sensitivity in magnetic resonance imaging using intermolecular double-quantum coherence. J Magn Reson Imaging, 16:733-40
Zhong J, Chen Z, Kwok WE, Kennedy SD (2001) Enhanced sensitivity to molecular diffusion with intermolecular double-quantum coherences: implications and potential applications. Magn. Reson. Imag., 19:33-39
Chen Z, Kennedy SD, Zhong J (2000) Quantitation of intermolecular dipolar effects in NMR spectroscopy and high order MSE MR imaging. Magma, 11:122-8
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E-Mail: Scott_Kennedy@urmc.rochester.edu
Scott Kennedy
Department of Biochemistry and Biophysics
University of Rochester School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester, New York 14642
Office: Medical Center Annex B-124
Telephone: (585) 275-7585; Fax: (585) 275-6007
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