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Personal Biography of William Stephen Brimijoin, Ph.D.

 

Research Interests:
Cholinergic neuroscience, especially the biology and toxicology of cholinesterases: novel enzyme inhibitors and reactivators produced with computational chemistry; molecular engineering of cholinesterases for therapeutic use; cellular and system-level toxicology of anticholinesterase insecticides; neurodegeneration induced by immunolesion with cholinesterase antibody; video-based, immunologic and radiometric assays of brain proteins.

Education and Academic Positions:
1964 B.A., Harvard (Experimental Psychology)
1969 Ph.D., Harvard (Pharmacology)
1971-75 Assistant Professor of Pharmacology, Mayo Medical School
1976-80 Associate Professor of Pharmacology, Mayo Medical School
1980-present Professor of Pharmacology, Mayo Medical School.
1983-87 Founding Dean, Mayo Graduate School
1992-2003 Chair, Department of Molecular Pharmacology, Mayo Clinic

Research Training and Visiting Professorships

1969-71 Postdoctoral training in neurochemistry with Julius Axelrod, Laboratory of Clinical Science, National Institute of Mental Health (Nobel Prize Winner for Medicine, 1970).
1978-79 Visiting Scientist, Karolinska Institute, Stockholm, Sweden. Immunofluorescence studies of neuropeptides (with Tomas Hökfelt)
1987-88 Visiting Professor, University of Wurzburg, Germany. Studies of catecholamine transporter proteins (with U. Trendelenburg and H. Bonisch)
1999-2002 (one month/yr) Visiting Professor, Institute of Materia Medica, Chinese Academy of Science, Shanghai, China (with Prof. Xi-Can Tang)

Review Panels
1989-93 N.I.H. Behavioral and Neuroscience Study Section, regular member
1992-2003 U.S. Environmental Protection Agency, Scientific Advisory Panels (average one/yr)
1997-99 U.S. Army Gulf War Grants Neurotoxicology Grants Review Board
1998, 2004 ILSI Risk Science Institute Panels on Developmental Neurotoxicity (Chair)

Awards
NIH Career Development Award (1975-80)
Javits Neuroscience Investigator Award, NINCDS (1987-94)
Senior U.S. Scientist Award, von Humboldt Foundation (Germany) (1987-88)
Mayo Distinguished Investigator Award (1994)
NIH research funding (R01 or PPG awards, 1971-present).

Selected Recent Publications (from 165 full-length articles):
Hammond PI, Kern C, Hong F, Kollmeyer TM, Pang Y-P, Brimijoin S. Cholinesterase reactivation in vivo with a novel bis-oxime optimized by computer-aided design. J. Pharmacol. Exp. Ther. 307: 190-196, 2003
Zhang HY, Brimijoin S, Tang XC. Apoptosis induced by b-amyloid25-35 in acetylcholinesterase-overexpressing neuroblastoma cells. Acta Pharmacol Sin. 24: 853-858, 2003
Hu W, Gray NW, Tang X-C, Brimijoin S. Amyloid-beta increases acetylcholinesterase expression in neuroblastoma cells by reducing enzyme degradation. J. Neurochem. 86: 470-478, 2003
Rees T and Brimijoin S. The role of acetylcholinesterase in the pathogenesis of Alzheimer disease.Drugs of Today, In press 2003.
Rees T, Hammond PI, Soreq H, Younkin S, and Brimijoin S Acetylcholinesterase promotes beta-amyloid plaques in cerebral cortex. J. Neurobiol. Aging. 24: 777-787, 2003
Pang Y-P, Kollmeyer TM, Hong F, Hammond PI, Haugabouk SP, Brimijoin S. Rational design of alkylene-linked bis-pyridiniumaldoximes as improved acetylcholinesterase reactivators. Chem. and Biol. 10: 491-502, 2003
Hammond PI, Craig TA, Kumar R and Brimijoin S. Regional and cellular distribution of DREAM in rat brain. Brain Res. Mol. Brain Res 111: 104-110, 2003.
Sun H, Pang YP, Lockridge O, and Brimijoin S. Re-engineering butyrylcholinesterase as a cocaine hydrolase. Molecular Pharmacology. 621: 220-224, 2002.
Sun H, Shen ML, Pang YP, Lockridge O, and Brimijoin S. Cocaine metabolism accelerated by a re-engineered human butyrylcholinesterase. J. Pharmacol. Exp. Ther. 302: 710-716. 2002
Brimijoin S, Shen ML, and Sun H. Radiometric solvent-partitioning assay for screening cocaine hydrolases and measuring cocaine levels in milligram tissue samples. Analytical Biochem. 309: 200-205, 2002.
Tang H and Brimijoin S. Death of preganglionic sympathetic neurons after surgical or immunologic lesion of peripheral processes. Exp. Neurol. 177: 105-114, 2002.
Sun H, El Yazal J, Brimijoin S, and Pang Y-P. Predicted Michaelis-Menten complexes of cocaine-butyrylcholinesterase: engineering effective butyrylcholinesterase mutants for cocaine detoxification. J. Biol. Chem. 276: 9330-9336, 2001
Tang H, Morgan BP, Brimijoin S. Complement regulatory proteins and selective vulnerability of neurons to lysis on exposure to acetylcholinesterase antibody. J. Neuroimmunol. 115: 53-63, 2001.
Sharma KV, Brimijoin S, Koenigsberger C, Bigbee J. Acetylcholinesterase modulates the adhesion of neuroblastoma cells. J. Neurosci. Res. 63: 165-175, 2001
Li B, Stribley JA, Ticu A, Xie W, Schopfer LM, Hammond P, Brimijoin S, Hinrichs S, Lockridge O. Abundant tissue butyrylcholinesterase and its possible function in the acetylcholineterase knockout mouse. J. Neurochem. 75:1320-1331, 2000
Atanasova E, Chiappa S, Wieben E and Brimijoin S. Novel messenger RNA and alternative promoter for murine acetylcholinesterase. J. Biol. Chem. 274: 21078-21084, 1999.
Brimijoin S. and Koenigsberger C. Cholinesterases in neural development, and toxicological implications. Env. Health Persp. 107: 59-64, 1999.
Koenigsberger C, Hammond P, and Brimijoin S. Developmental expression of acetyl- and butyrylcholinesterase in the rat: enzyme and mRNA levels in embryonic dorsal root ganglia. Brain Res., 787: 248-258, 1998.
Brimijoin S and Hammond P. Transient expression of acetylcholinesterase mRNA and enzyme activity in developing rat thalamus studied by quantitative histochemistry and in situ hybridization. Neurosci. 71: 555-565, 1996.
Pang Y-P, Hong F, Quiram P, Jelacic T, and Brimijoin S. Synthesis of alkylene linked bis-THA and alkylene linked benzyl-THA as highly potent and selective inhibitors and molecular probes of acetylcholinesterase. J. Chem. Soc., Perkin Trans. I. 2: 171-176, 1997. Hammond P,
Jelacic T, Padilla S, and Brimijoin S. Quantitative, video-based histochemistry to measure regional effects of anticholinesterase pesticides in rat brain. Anal. Biochem., 241: 82-92, 1996.
Pang Y-P, Quiram P, Jelacic T, F. Hong, and Brimijoin S. Highly potent, selective, and low-cost bis-tetrahydroaminacrine inhibitors of acetylcholinesterase: Steps toward a new generation of drugs for cholinergic therapy of Alzheimer's disease. J. Biol. Chem., 271: 23646-23649, 1996.
Brimijoin S. Using antibodies to unwire the sympathetic nervous system. News in Physiol. Sci. 10: 101-106, 1995.

US Patents
Y.-P. Pang and S. Brimijoin. THA Analogs Useful as Cholinesterase Inhibitors. Patent Number 5,886,007. March 23, 1999.
Y.-P. Pang and S. Brimijoin. Bifunctional Acetylcholinesterase Reactivators. Patent Number 5,929,093. July 27, 1999.


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