Dr. Johnson received a BS in Biology (1984) and MS in Pharmacology (1986) from the University of Minnesota-Duluth, and a PhD 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 Molecular and Environmental Toxicology Center which oversees the training of PhD candidates in fields ranging from neurodegeneration to bioremediation. He is also the Director of the undergraduate BS Pharmacology and Toxicology program.
Dr. Johnson's research interests are focused around signal transduction, transcriptional control of neuroprotective genes and neurodegenerative diseases. Transcriptional activation of the major phase II detoxification enzymes and/or antioxidant genes has been traced to a cis-acting element called the antioxidant responsive element (ARE). Nrf2 (NF-E2-related factor 2) is the key transcription factor mediating ARE activation. Microarray-based gene expression profiling has identified a pool of potential ARE-driven genes. This common pool of genes includes multiple detoxification enzymes and antioxidant genes, which coordinate to promote glutathione synthesis, NADPH production, and free radical scavenging. These changes are proposed to protect cells from oxidative stress-induced cell death. Increased oxidative stress is associated with neuronal cell death during the pathogenesis of multiple chronic neurodegenerative diseases including Parkinson's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, and Alzheimer's disease. The central hypothesis is that the Nrf2-ARE pathway is a novel neuroprotective pathway that when activated can confer resistance to a variety of oxidative stress-related neurodegenerative insults. Dr. Johnson's laboratory is currently studying this pathways potential for modulating neurodegeneration both in vitro and in vivo. The importance of the Nrf2-ARE pathway is being evaluated through multiple techniques including: 1) genomic and proteomic changes associated with Nrf2-ARE activation; 2) transplantation of genetically engineered astrocytes or neural progenitor cells to determine their effects on chemical and genetic models of neurodegeneration; 3) construction of cell-specific Nrf2 transgenic mice to determine their effects on chemical and genetic models of neurodegeneration; and 4) high-throughput screens for novel small molecule activators of the Nrf2-ARE pathway for the development of new potential therapeutics. Mouse models for Parkinson's disease, Alzheimer's disease, Huntington's disease and Amyotrophic Lateral Sclerosis are being studied, and in a newly initiated collaboration with Dr. Marina Emborg at the primate center, they are beginning Nrf2-ARE studies in non-human primate models of Parkinson's disease.