The Johnson Laboratory
Faculty > Jeffrey A. Johnson
Jeffrey A. Johnson
Professor, Division of Pharmaceutical Sciences
jajohnson@pharmacy.wisc.edu
Organ System/Disease Focus
Neurodegenerative disease, Alzheimer’s, Parkinson’s, ALS, Huntington’s
Aligned Research Focus
Basic stem cell science, transplantation of genetically engineering stem cells
Research Description
Oxidative stress is likely a principal factor in the development of many chronic neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's and Amyotrophic Lateral Sclerosis. Oxidative stress can be defined as an imbalance in which free radicals and their products exceed the capacity of 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 defense mechanisms in the brain by activating multiple antioxidant defense genes simultaneously through activation of the Nrf2-ARE (antioxidant response element) pathway. Transplantion of genetically engineered neural stem cells overexpressing Nrf2 is one approach used to boost this protective pathway.
Additional research involving neural stem cells addresses the role of Nrf2 in neuronal and glial differentiation, differential sensitivity of neurons and astrocytes to oxidative stress-induced cell death, and screening for small molecule activator of the Nrf2-ARE pathway. In our laboratory, we use chemical and genetic models of Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and Amyotrophic Lateral Sclerosis (Lou Gehrig’s disease).
Selected References
Li J, Spletter ML, Johnson DA, Wright LS, Svendsen CN, Johnson JA. Rotenone induced caspase 9/3 independent and dependent cell death in undifferentiated and differentiated human neural stem cells. J. Neurochem. 92(3):462-76. 2004.
Li J, Johnson DA, Calkins MJ, Wright LS, Svendsen CN, Johnson JA. Stabilization of Nrf2 by tBHQ Confers Protection Against Oxidative Stress-induced Cell Death in Human Neural Stem Cells. Toxicol. Sci. 83(2):313-28. 2004.
Calkins MJ, Jakel RJ, Johnson DA, Chan K, Kan YW, Johnson JA. Protection from mitochondrial complex II inhibition in vitro and in vivo by Nrf2-mediated transcription. Proc. Natl. Acad. Sci. USA. 102(1):244-9. 2005.
Li J, Spletter ML, Johnson JA. Dissecting tBHQ induced ARE driven gene expression through long and short oligonucleotide arrays. Physiol. Genomics 21(1):43-58. 2005.