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Name: Edward D.  Hall
Position Type: Chair
Appointment Start Date: 07/01/02
Appointment End Date: 06/30/07
Area of Specialty: Neuropharmacology
Summary Vita: Principal Investigator/Program Director (Last, First, Middle): Hall, Edward D. BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME Edward D. Hall POSITION TITLE Director, Spinal Cord & Brain Injury Research Center and Professor of Anatomy & Neurobiology, Neurology & Neurosurgery eRA COMMONS USER NAME EDHALL EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) INSTITUTION AND LOCATION DEGREE (if applicable) YEAR(s) FIELD OF STUDY Mount Union College B.S. 1972 Biology Cornell University Graduate School of Medical Sciences Ph.D. 1976 Pharmacology Cornell University Medical College Post-Doc 1976-1977 Neuropharmacology A. Positions and Awards 1978-1981 Assistant Professor of Pharmacology, Northeastern Ohio Universities College of Medicine (NEOUCOM), Rootstown, Ohio. 1982 Associate Professor of Pharmacology, NEOUCOM (granted with tenure) 1982-1989 Adjunct Associate Professor of Pharmacology, NEOUCOM 1990-1998 Adjunct Professor of Pharmacology, NEOUCOM 1982-1984 Research Scientist II, CNS Diseases Research. The Upjohn Co., 1985-1990 Senior Research Scientist III, CNS Diseases Research. The Upjohn Co., 1990-1992 Senior Scientist IV, CNS Diseases Research, The Upjohn Co. 1992-1996 Senior Scientist V, CNS Diseases Research. The Upjohn Co. 1996-1997 Distinguished Scientist VI, CNS Diseases Research. Pharmacia & Upjohn 1997-1999 Senior Research Fellow and Group Leader, Neuroscience Therapeutics. Parke-Davis Pharmaceutical Research 1999-2000. Senior Research Fellow and Section Director, Neurology, Neuroscience Therapeutics, Parke-Davis Pharmaceutical Research 2000-2002 Senior Director, CNS Pharmacology, Pfizer Global Research & Development, 2002-Present Director, Spinal Cord & Brain Injury Research Center and Professor of Anatomy & Neurobiology, Neurology and Neurosurgery, University of Kentucky, July, 2002-Present Awards Fred Kagan Award "For Outstanding Achievement in Discovery Research," The Upjohn Company, 1988. Upjohn Achievement in Science and Medicine Award, 1991. B. Selected Peer-Reviewed Publications (from 148; in chronological order) 1. Hall, E.D. High dose glucocorticoid treatment improves neurological recovery in head-injured mice. J. Neurosurg. 62:882-887, 1985. 2. Hall, E.D., J.M.McCall, P.A.Yonkers, R.L.Chase and J.M.Braughler. A non-glucocorti¬coid steroid analog of methylprednisolone duplicates its high dose pharmacology in models of CNS trauma and neuronal membrane damage. J. Pharmacol. Exp. Ther. 242:137-142, 1987. 3. Hall, E.D., P.A.Yonkers, J.M.McCall and J.M.Braughler. Effects of the 21-aminosteroid U-74006F on experimental head injury in mice. J. Neurosurg. 68:456-461, 1988. 4. Hall, E.D., P.A.Yonkers, K.L.Horan and J.M.Braughler. Correlation between attenuation of post-traumatic spinal cord ischemia and preservation of spinal tissue vitamin E by the 21-aminoster¬oid lipid peroxidation inhibitor U-74006F: Evidence for an in vivo antioxidant mechanism. J. Neurotrauma 6:169-176, 1989. 5. Panter, S.S., J.M.Braughler and E.D.Hall. Dextran-coupled deferoxamine improves outcome in a murine model of head injury. J. Neurotrauma 9:47-53, 1992. 6. Hall, E.D., P.K.Andrus and P.A.Yonkers. Brain hydroxyl radical generation in acute experimental head injury. J. Neurochem. 60:588-594, 1993. 7. Smith, S.L., P.K.Andrus, J.R.Zhang and E.D.Hall. Direct measurement of hydroxyl radical levels, lipid peroxidation and blood-brain barrier disruption following unilateral head injury in the rat. J. Neurotrauma 11:393-404, 1994. 8. Zhang, J.R., H.M.Scherch and E.D.Hall. Direct measurement of lipid hydroperoxides in iron-dependent spinal neuronal injury. J. Neurochem. 66:355-361, 1996. 9. Fici, G.J., J.S. Althaus, E.D. Hall and P.F. VonVoigtlander. Protective effects of tirilazad mesylate in a cellular model of peroxynitrite toxicity. Res. Commun. Mol. Path. Pharmacol. 91:357-371, 1996. 10. Hall, E.D., S.L. Smith and J.A. Oostveen. Inhibition of lipid peroxidation attenuates axotomy-induced apoptotic degeneration of facial motor neurons in neonatal rats. J. Neurosci. Res. 44:293-299, 1996. 11. Smith, S.L. and E.D.Hall. Mild pre- and post-traumatic hypothermia attenuates blood-brain barrier damage following controlled cortical impact injury in the rat. J. Neurotrauma 13:1-9, 1996. 12. Hall, E.D., P.K.Andrus, S.L.Smith, T.J.Fleck, H.M.Scherch, B.S.Lutzke, G.A.Sawada, J.S.Althaus, P.F.VonVoigtlander, G.E.Padbury, P.G.Larsen, J.R.Palmer and G.L.Bundy. Pyrrolopyrimidines: Novel brain-penetrating antioxidants with neuroprotective activity in brain injury and ischemia models. J. Pharmacol. Exp. Ther. 281:895-904. 1997. 13. Hall, E.D., J.A. Oostveen, D.K. Anderson and C.W. Thomas. Immunocytochemical method for investigating in vivo neuronal oxygen radical-induced lipid peroxidation. J. Neurosci. Methods 76:115-122, 1997. 14. Oostveen, J.A., E. Dunn, D.B. Carter and E.D. Hall. Two novel pyrrolopyrimidine, lipid peroxidation inhibitors PNU-101033E and PNU-104067F suppress amyloid precursor protein and apolipoprotein E immunostaining following transient forebrain ischemia in gerbils. J. Cereb. Blood Flow & Metab. 18:539-547, 1998. 15. Smith, S.L., P.G. Larson and E.D. Hall. A comparison of the effects of tirilazad on subarachnoid hemorrhage-induced blood-brain barrier permeability in male and female rats. J. Stroke and Cerebrovasc. Disorders 6:389-393, 1997. 16. Gurney, M.E., T.J. Fleck, C.S. Himes and E.D. Hall. Riluzole preserves motor function in FALS transgenic mice. Neurology 50:62-66, 1998. 17. Hall, E.D., P.K. Andrus, J.A. Oostveen, T.J. Fleck and M.E. Gurney. Relationship of oxygen radical-induced lipid peroxidative damage to disease onset and progression in a transgenic model of familial ALS. J. Neurosci. Res. 53:66-77,1998. 18. Hall, E.D., J.A. Oostveen and M.E. Gurney. Relationship of Microglial and Astrocytic Activation to disease onset and progression in a transgenic model of familial ALS. Glia 23: 249-256, 1998. 19. Smith, S.L., P.K. Andrus, D.D. Gleason and E.D. Hall. An infant rat model of the shaken baby syndrome: preliminary characterization and evidence for the role of free radicals in cortical hemorrhaging and progressive neuronal degeneration. J. Neurotrauma 15:693-705, 1998. 20. Smith, S.L. and E.D. Hall. Tirilazad widens the therapeutic window for riluzole-induced attenuation of progressive cortical degeneration in an infant rat model of the shaken baby syndrome. J. Neurotrauma 15:707-719, 1998. 21. Althaus, J.S., T.J. Fleck, D.A. Becker, E.D. Hall and P.F. VonVoigtlander. Azulenyl nitrones: colorimetric detection of oxyradical end products and neuroprotection in the gerbil transient forebrain ischemia model. Free Rad. Biol. Med. 24:738-744, 1998. 22. Carroll, R.T., P. Galatsis, S. Borosky, K.K. Kopec; V. Kumar, J. Althaus and E.D. Hall. 4-Hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol) inhibits peroxynitrite-mediated phenol nitration. Chem. Res. Toxicol. 13:294-300, 2000 23. Althaus, J.S., K.R. Schmidt, S.T. Fountain, M.T. Tseng, R.T. Carroll, P. Galatsis and E. D. Hall. LC-MS/MS detection of peroxynitrite-derived 3-nitrotyrosine in rat microvessels. Free Rad. Biol. Med. 29:1085-1095, 2000. 24. Roof, R.L. and E.D. Hall. Estrogen-related gender difference in survival rate and cortical blood flow after impact-acceleration head injury in rats. J. Neurotrauma 17:1155-1169, 2000. 25. Kupina, N.C., R. Nath, E.E. Bernath, J. Inoue, M. Azuma, P-W. Yuen, K.K.W. Wang and E.D. Hall. The novel calpain inhibitor SJA6017 improves functional recovery after delayed administration in a mouse model of diffuse head injury. J. Neurotrauma 18: 1229-1240, 2001. 26. Roof, R.L, G.P. Schielke, X. Ren and E.D. Hall. A comparison of chronic functional outcome following two MCA models in rats. Stroke 32:2648-2657, 2001. 27. Kupina, N.C., M.R. Detloff, S. Dutta and E.D. Hall. The neuroimmunophilin ligand V-10,367 is neuroprotective following 24-h delayed administration in a mouse model of diffuse traumatic brain injury. J. Cereb. Blood Flow & Metab. 22:1212-1221, 2002. 28. Kupina, N.C., M.R. Detloff, W.F. Bobrowski, B.J. Snyder and E.D. Hall. Cytoskeletal protein degradation and neurodegeneration evolves differently in males and females following experimental head injury. Exp. Neurol. 180: 55-72, 2003. 29. Hall, E.D., M.E. Detloff, K. Johnson and N.C. Kupina. Peroxynitrite-mediated protein nitration and lipid peroxidation in a mouse model of traumatic brain injury. J. Neurotrauma 21:9-20, 2004. 30. Hall, E.D., P.G. Sullivan, T.R. Gibson, K.M. Pavel, B.M. Thompson and S.W. Scheff. Spatial and temporal characteristics of neurodegeneration after controlled cortical impact in mice: more than a focal injury. J. Neurotrauma 22:252-265, 2005 31. Hall, E.D., T.R. Gibson and K.M. Pavel. Lack of a gender difference in post-traumatic neurodegeneration in the mouse controlled cortical impact injury model. J. Neurotrauma 22:669-679, 2005. 32. Singh, I. N., P.G. Sullivan, Y. Deng, L.H. Mbye and E.D. Hall. Time course of post-traumatic mitochondrial oxidative damage and dysfunction in a mouse model of focal traumatic brain injury: implications for neuroprotective therapy. J. Cereb. Blood Flow & Metab. 26:1407-1418, 2006. 33. Thompson, S.N., T.R. Gibson, B.M. Thompson, Y. Deng and E.D. Hall. Relationship of calpain-mediated proteolysis to the expression of axonal and synaptic plasticity markers following traumatic brain injury in mice. Exp. Neurol. 201:253-265, 2006. 34. Chen, Q., S. Wang, S.N. Thompson, E.D. Hall and R.P. Guttmann. Identification and characterization of PEBP as a calpain substrate. J. Neurochem. 99:1133-1141, 2006. Selected Chapters and Reviews 1. Hall, E.D. Free radicals and CNS injury. Critical Care Clinics 5:793-805, 1989. 2. Hall, E.D. The neuroprotective pharmacology of methylprednisolone: A review. J. Neurosurg. 76:13-22, 1992. 3. Hall, E.D., P.A.Yonkers, P.K.Andrus, J.W.Cox and D.K.Anderson. Biochemistry and pharmacology of lipid antioxidants in acute brain and spinal cord injury. J. Neurotrauma 9(Suppl. 2):S425-S442, 1992. 4. Hall, E.D. Degenerative and Regenerative Events in the Central and Peripheral Nervous Systems. In: Comprehensive Toxicology, I.G. Sipes, C.A. McQueen and A.J. Gandolfi (eds.), Chapter 3 in Vol 11: Nervous System and Behavioral Toxicology, H.E. Lowndes and K. Reuhl (eds.), Pergamon Press, Oxford, pp.41-58, 1997. 5. Hall, E.D. Lazaroids: Mechanisms of Action and Implications for Disorders of the CNS. The Neuroscientist 3:42-51, 1997. 6. Hall, E.D. Acute therapeutic interventions: free radical scavengers and antioxidants. Neurosurg. Clin. North Am. 8:195-206. 7. Hall, E.D. and Andrus, P.K. Measurement of oxygen radicals and lipid peroxidation in neural tissue. Current Protocols in Neuroscience, 2000. 8. Roof, R. and E.D. Hall. Gender differences in acute CNS trauma and stroke: neuroprotective effects of estrogen and progesterone. J. Neurotrauma 17:367-388, 2000. 9. Hall, E.D. Drug development in spinal cord injury, what is the FDA looking for? J. Rehab. Res. Dev. 40 (Suppl 1):81-92,2003. 10. Hall, E.D. Acute Treatment Strategies for Spinal Cord Injury. Chapter 57 in: Spinal Cord Medicine: Principles and Practice, (V.W. Lin et al, eds.), Demos Publishing Co., New York, pp. 797-805, 2003. 11. Hall, E.D. and P.G. Sullivan. Preserving Function in Acute Nervous System Injury. In: From Neuroscience to Neurology: Neuroscience, Molecular Medicine, and the Therapeutic Translation of Neurology, (S.Waxman, Ed.), Elsevier/Academic Press, Amsterdam, pp. 35-59, 2004. 12. Hall, E.D. and J.E. Springer. Neuroprotection and acute spinal cord injury: a reappraisal. NeuroRx 1:80-100, 2004. C. Current Grant Support NIH-NINDS 5RO1 NS46566-03 “Peroxynitrite-Induced Oxidative Damage in TBI” Role: PI 2/1/ 04-1/31/08 Total Direct Costs $925,000 Kentucky Spinal Cord & Head Injury Research Trust “Novel Therapy for Traumatic Brain Injury” Role:PI 1/15/04-1/14/07 Total Direct Costs: $287,093 NIH-NINDS 1 P30 NS051220-01 “UK Spinal Cord & Brain Injury Research Center Core Grant” Role: PI 5/1/05-4/30/10 Total Direct Costs $2,224,546 NIH-NIDA 1T32 DA 022738-01 “Therapeutic Strategies for Neurodegeneration Training Grant” Role: PI and Program Director 10/1/06-9/30/11 Total Direct Costs $1,240,734 University of Kentucky Commonwealth Collaborative “Biomarkers for Brain and Spinal Cord Damage” Role: PI 3/1/06-2/28/07 Total Direct Costs $10,000 D. Pending Grant Support NIH-NINDS 1R01 NS058687A “Newer Small Molecule Calpain Inhibitors for TBI” Role: PI NIH-NINDS 1R01 NS056084-01 “Mitochondrial Targeted Therapeutic Interventions in Spinal Cord Injury” Role: Co-PI
Highest Degree: DrPH
Professional Affiliations: •Section Editor, Journal of Neurotrauma, 1995-Present •Editorial Board, Neurotherapeutics, 2002-Present •Editorial Board, Restorative Neurology & Neuroscience, 2005-Present •Editorial Board, Biochemical Pharmacology, 2006-Present •Regular Member of NINDS CND Study Section, October, 2004 - present •NINDS Spinal Muscular Atrophy Project Steering Committee, September, 2003-Present
Primary Research Focus: Discovery of novel neuroprotective pharmacological approaches for acute traumatic spinal cord and brain injury.
Key Contributions: MOST SIGNIFICANT RESEARCH AND DRUG DISCOVERY ACCOMPLISHMENTS RELATED TO FIELD OF STUDY •Demonstration of the ability of high dose glucocorticoid steroid treatment to retard anterograde (Wallerian) degeneration of motor nerves •Demonstration of the effects of glucocorticoid steroids on CNS excitability and serotonergic and noradrenergic transmission and the possible relationship of these effects to the pathogenesis of depression •Demonstration of the importance of oxygen radical-induced lipid peroxidation in the pathophysiology of acute traumatic brain and spinal cord injury •Discovery and development of high dose (antioxidant) methylprednisolone (Solu MedrolR) treatment of acute spinal cord injury (now is standard of treatment for human spinal cord injuries, and is approved in most countries) •Discovery and development of the "lazaroid" non-glucocorticoid 21-aminosteroid tirilazad mesylate (FreedoxR) for acute neurological injuries (now on market in several countries for aneurysmal subarachnoid hemorrhage) •Discovery of the 2-methylaminochroman (U78517) and pyrrolopyrimidine neuroprotective antioxidants •Demonstration of the neuroprotective properties of the D2/D3 agonist pramipexole (MirapexR) on dopaminergic neurons (now on market for Parkinson's disease in most countries) •Demonstration of gender differences in susceptibility to acute cerebral ischemia and traumatic brain injury •Demonstration of the neuroprotective properties of kappa opioid agonists (e.g. U-50488, U-62066E) in acute traumatic and ischemic CNS injury models •Demonstration of the role of the reactive oxygen species peroxynitrite in traumatic brain injury and the neuroprotective efficacy of peroxynitrite scavenging compounds
Publications: Hall, E.D., P.G. Sullivan, T.R. Gibson, K.M. Pavel, B.M. Thompson and S.W. Scheff. Spatial and temporal characteristics of neurodegeneration after controlled cortical impact in mice: more that a focal brain injury. J. Neurotrauma 22:252-265, 2005. Hall, E.D., K.M. Pavel and T.R. Gibson. Lack of gender difference in post-traumatic neurodegeneration in the mouse controlled cortical impact injury model. J. Neurotrauma 22:669-679, 2005. Singh, I. N., P.G. Sullivan, Y. Deng, L.H. Mbye and E.D. Hall. Time course of post-traumatic mitochondrial oxidative damage and dysfunction in a mouse model of focal traumatic brain injury: implications for neuroprotective therapy. J. Cereb. Blood Flow & Metab. 26:1407-1418, 2006. Thompson, S.N., T.R. Gibson, B.M. Thompson, Y. Deng and E.D. Hall. Relationship of calpain-mediated proteolysis to the expression of axonal and synaptic plasticity markers following traumatic brain injury in mice. Exp. Neurol. 201:253-265, 2006. Chen, Q., S. Wang, S.N. Thompson, E.D. Hall and R.P. Guttmann. Identification and characterization of PEBP as a calpain substrate. J. Neurochem. 99:1133-1141, 2006. Xiong, Y., A.G. Rabchevsky and E.D. Hall. Role of peroxynitrite in secondary oxidative damage after spinal cord injury. J. Neurochem., in press.