Jeffrey Johnson
Ph.D. University of Wisconsin
Professor, Pharmacy

Contact Information:
School of Pharmacy
University of Wisconsin
777 Highland Ave.
Madison, WI 53705
Phone: (608) 262-2893
Fax: (608) 262-5345
E-mail: jajohnson@pharmacy.wisc.edu
Web: Pharmacy

Research Statement

The focus of my laboratory is Molecular Neuropharmacology/Neurotoxicology. Oxidative stress is believed to be a principal factor in the development of many chronic neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's and Amyotrophic Lateral Sclerosis. In general, oxidative stress can be defined as an imbalance in which free radicals and their products exceed the capacity cellular antioxidant defense mechanisms. A gain in product formation or loss in protective mechanisms can disturb this equilibrium leading to programmed cell death (PCD). PCD occurs normally with the aging process but appears to be accelerated by the pathology of Alzheimer's Disease, presumably due to increased oxidative stress caused by beta2-amyloid. We know, there fore, the driving force for the development of Alzheimer's Disease; however, we have little knowledge of how the different genes and proteins contributing to antioxidant defenses are regulated in brain. My laboratories goal is to discover ways to increase the defense mechanisms in brain by activating multiple antioxidant defense genes simultaneously through activation of the antioxidant response element (ARE). A process we refer to a programmed cell life (PCL). Any increase in the forces that drive PCD therefore must be balanced by increasing the forces driving PCL or the cell will die.

Present work in the laboratory is designed to: 1) Determine the molecular mechanism(s) by which tert-butyl hydroquinone (tBHQ) activates the ARE; 2) Characterize the expression pattern and regulation of the ARE in vivo and in primary neuronal and glial cultures derived from ARE transgenic reporter mice; 3) determine if ARE activation can block apoptosis induced by oxidative stress and beta2-amyloid; 4) identify and understand the regulation of ARE-driven genes in mouse and human primary neuronal and glial cultures through the use of Affymetrix oligonucleotide microarrays; 5) characterize the role of Nrf2 in regulation of ARE activation and PCL in the brains of Nrf2 null mice; and 6) determine the effect of overexpression of amyloid precursor protein on antioxidant gene expression, neuronal survival and plaque formation in Nrf-2 null mice.

Representative Publications

Li, J. and J.A. Johnson (2002). Differential gene expression patterns revealed by oligonucleotide versus long cDNA microarrays. Toxicol. Sci. In Press.

Stein, T.D. and J.A. Johnson (2002). Lack of Neurodegeneration in Transgenic Mice Overexpressing Mutant Amyloid Precursor Protein is Associated with Increased Levels of Transthyretin and Activation of Cell Survival Pathways. J. Neurosci. 22:7380-7388.

Johnson, D.A., Xu, W., Andrews, G.A. and J.A. Johnson (2002). Activation of the Antioxidant Response Element in Primary Cortical Neuronal Cultures Derived from Transgenic Reporter Mice. J. Neurochem. 81:1233-1241.

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Awards & Honors