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Education:

• B.S. 1984 Biology University of Minnesota-Duluth
• M.S. 1986 Pharmacology University of Minnesota-Duluth
• Ph.D. 1992 Environ. Toxicology University of Wisconsin
• Postdoctoral 1995 Neuroscience University of Washington

Overview

Dr. Johnson received a B.S. in Biology (1984) and M.S. in Pharmacology (1986) from the University of Minnesota-Duluth, and a Ph.D. in Environmental Toxicology (1992) from the University of Wisconsin. He did postdoctoral training in the Department of Pharmacology at the University of Washington and spent four years as an assistant professor at the University of Kansas Medical Center before joining the University of Wisconsin School of Pharmacy faculty in 1999. Dr. Johnson is the Director of the Pharmacology and Toxicology B.S. program. He is also a member of the Waisman Center, Center for Neuroscience, Neuroscience Training Program, Cellular and Molecular Biology Training Program, M.D/Ph.D. Training Program, Molecular and Environmental Toxicology Training Program, and Molecular and Cellular Pharmacology Training Program.

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 in chronic neurodegenerative diseases due in part to increased oxidative stress. My laboratory's 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 as 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) Identification of novel small molecules that activate the Nrf2-ARE pathway; 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 the neuroprotective efficacy of transplanted astrocytes and/or neural progenitor cells overexpressing Nrf2; 4) characterize the how changes in glutathione levels effect neurodegeneration; and 5) determine the effect of soluble amyloid precursor protein cleavage products on gene expression and neuronal survival. The laboratory is actively using chemical and genetic models of Parkinson's disease, Alzheimer's disease, Huntington's disease, Amyotrophic Lateral Sclerosis (Lou Gehrig's disease), and Epilepsy.

Work-Related Interests/Research:

Signal transduction, transcriptional control of neuroprotective genes and neurotoxicity.

Highlighted Publications:

• Lee, J.M., Shih, A.Y., Murphy, T.H. and J.A. Johnson (2003). NF-E2-related factor 2 mediates neuroprotection against mitochondrial complex I inhibitors and increased concentrations of intracellular calcium in primary cortical neurons. J. Biol. Chem. 278 (39): 37948-56.
• Kraft, A.D., Johnson, D.A. and J.A. Johnson (2004). Nuclear factor E2-related factor 2-dependent antioxidant response element activation by tert-butylhydroquinone and sulforaphane occurring preferentially in astrocytes conditions neurons against oxidative insult. J Neurosci. 24(5):1101-12.
• Lee, J.M., Chan, K., Kan, Y.W. and J.A. Johnson (2004). Targeted Disruption of Nrf2 Causes Regenerative Immune-Mediated Hemolytic Anemia. Proc. Natl. Acad. Sci. USA 101(26):9751-6.
• Stein, T.D., Anders, N.J., DeCarli, C., Chan, S.L., Mattson, M.P. and J.A. Johnson (2004). Neutralization of transthyretin reverses the neuroprotective effects of sAPPalpha in APPSw mice resulting in tau phosphorylation and loss of hippocampal neurons: support for the amyloid hypothesis. J. Neurosci. 24(35):7707-17.
• Li, J., Spletter, M.L., Johnson,, D.A., Wright, L.S., Svendsen, C.N. and J.A. Johnson (2004). Rotenone induced caspase 9/3 independent and dependent cell death in undifferentiated and differentiated human neural stem cells. J. Neurochem. 92(3):462-76.
• Li, J., Stein, T.D. and J.A. Johnson (2004). Genetic Dissection of Systemic Autoimmune Disease in Nrf2 Deficient Mice. Physiol. Genomics 18(3):261-72.
• Li, J., Johnson,, D.A., Calkins, M.J., Wright, L.S., Svendsen, C.N. and J.A. Johnson (2004). Stabilization of Nrf2 by tBHQ Confers Protection Against Oxidative Stress-induced Cell Death in Human Neural Stem Cells. Toxicol. Sci. 83(2):313-28.
• Lee, J.M., Li, J., Johnson,, D.A., Stein, T.D., Kraft, A.D., Calkins, M.J., Jakel, R. and J.A. Johnson (2005). Nrf2, a Multi-organ Protector? FASEB J. 19(9):1061-6.
• Jakel, R.J., Kern, J.T., Johnson, D.A. and J.A. Johnson (2005). Induction of the protective antioxidant response element pathway by 6-hydroxydopamine in vivo and in vitro. Toxicol. Sci. 87(1):176-186.
• Calkins, M.J., Jakel, R.J., Johnson, D.A., Chan K., Kan Y.W. and J.A. Johnson (2005). Protection from mitochondrial complex II inhibition in vitro and in vivo by Nrf2-mediated transcription. Proc. Natl. Acad. Sci. USA. 102(1):244-9.
• Hagemann, T.L., Gaeta, S.A., Smith, M.A., Johnson, D.A., Johnson, J.A. and A. Messing (2005). Gene expression analysis in mice with elevated glial fibrillary acidic protein and Rosenthal fibers reveals a stress response followed by glial activation and neuronal dysfunction. Hum. Mol. Genet. 14(16):2443-58.
• Li, J., Spletter, M.L. and J.A. Johnson (2005). Dissecting tBHQ induced ARE driven gene expression through long and short oligonucleotide arrays. Physiol. Genomics 21(1):43-58.
• Keller, U.A., Huber, M., Beyer, T.A. Siemes, C., Kümin, A., Braun, S., Bugnon, P., Mitropoulos, V., Johnson, D.A., Johnson, J.A., Hohl, D. and S. Werner (2006). Nrf transcription factors in keratinocytes are essential for skin tumor prevention but not for wound healing. Mol. Cell. Biol. 26(10):3773-84.
• Kraft, A.D., Lee, J.M., Johnson, D.A., Kan Y.W. and J.A. Johnson (2006). Nrf2-mediated actions of the antioxidant response element are essential for the cellular damage response to kainic acid. J. Neurochem. 98(6):1852-65.
• Jakel, R.J., Townsend, J.A. Kraft, A.D. and J.A. Johnson (2007). Nrf2-mediated protection against 6-hydroxydopamine. Brain Res. 1144C:192-201
• Liu, Y., Kern, J.T., Walker, J.R., Johnson, J.A., Schultz, P.G. and H. Luesch (2007). A genomic screen for activators of the antioxidant response element. Proc. Natl. Acad. Sci. USA. 104(12):5205-10.
• Kraft, A.D., Resch, J.M., Johnson, D.A. and J.A. Johnson (2007). Activation of the Nrf2-ARE pathway in muscle and spinal cord during ALS-like pathology in mice expressing mutant SOD1. Exp. Neurol. 207(1):107-17.
• Choi, S.H., Leight, S., Lee, V.M.-Y., Li, T., Wong, P.C., Johnson, J.A., Saraiva, M. and S.S. Sisodia (2007). Accelerated A?eta deposition in APPswe/PS1DE9 mice with hemizygous deletions of TTR (Transthyretin). J. Neurosci. 27(26):7006-10.
• Vargas, M.R., Johnson, D.A., Sirkis, D.W., Messing, A. and J.A. Johnson (2008). Nrf2 activation in astrocytes protects against neurodegeneration in mouse models of familial amyotrophic lateral sclerosis. J. Neurosci. 28(50):13574-81.
• Chen PC, Vargas MR, Pani AK, Smeyne RJ, Johnson DA, Kan YW, and J.A. Johnson (2009). Nrf2-mediated neuroprotection in the MPTP mouse model of Parkinson's disease: Critical role for the astrocyte. Proc Natl Acad Sci U S A. 106(8):2933-8.
• Dowell JA, Johnson JA, Li L. (2009). Identification of Astrocyte Secreted Proteins with a Combination of Shotgun Proteomics and Bioinformatics. J Proteome Res. 8(8):4135-43
• Liu L, Hou J, Du J, Chumanov RS, Xu Q, Ge Y, Johnson JA, Murphy RM. (2009). Differential modification of Cys10 alters transthyretin's effect on beta-amyloid aggregation and toxicity. Protein Eng Des Sel. 22(8):479-88
• Review: Calkins MJ, Johnson DA, Townsend JA, Vargas MR, Dowell JA, Williamson TP, Kraft AD, Lee JM, Li J, and JA Johnson (2008). The Nrf2/ARE pathway as a potential therapeutic target in neurodegenerative disease. Antioxid Redox Signal. 2008 Aug 21. [Epub ahead of print]
• Review: Johnson JA, Johnson DA, Kraft AD, Calkins MJ, Jakel RJ, Vargas MR, and PC Chen (2008). The Nrf2-ARE pathway: an indicator and modulator of oxidative stress in neurodegeneration. Ann N Y Acad Sci. 1147:61-9.
• Review: Vargas MR, Johnson JA. (2009). The Nrf2-ARE cytoprotective pathway in astrocytes. Expert Rev Mol Med. 3;11:e17.