Professor in Pharmaceutical Sciences 

School of Pharmacy
6125 Rennebohm Hall

Research Interests:Alzheimer’s. Amyotrophic Lateral Sclerosis. Huntington’s. Parkinson’s. Autoimmune Disease. How Antioxidant Response Element (ARE)-driven genes block cell death.


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.

  • Yang DT, Joshi G, Cho PY, Johnson JA, Murphy RM (2013). Transthyretin as both Sensor and Scavenger of Abeta Oligomers. Biochemistry, 52(17):2849-61.
  • Fischedick JT, StandifordM, Johnson DA, Johnson JA (2013). Structure activity relationship of phenolic diterpenes from Salvia officinalis as activators of the nuclear factor E2-related factor 2 pathway. Bioorg Med Chem. 21(9):2618-22.
  • Vargas MR, Burton NC, Johnson DA, Schäfer M, Werner S, Messing A, Johnson JA (2013). Absence of Nrf2 or its selective over-expression in neuronal and muscle cells does not affect survival in ALS-linked mutant hSOD1 mouse models. PLoS One 8(2):e56625.
  • Zhang L, Johnson DA, Johnson JA (2013). Deletion of Nrf2 impairs functional recovery, reduces clearance of myelin debris and decreases axonal remyelination after peripheral nerve injury. Neurobiol Dis. 54:329-38.
  • Gan L, Vargas MR, Johnson DA, Johnson JA (2012). Astrocyte-specific Overexpression of Nrf2 Delays Motor Pathology and Synuclein Aggregation throughout the CNS in the Alpha-synuclein Mutant (A53T) Mouse Model. J. Neurosci. 32(49): 17775-17787.
  • Williamson TP, Amirahmadi S, Joshi G, Kaludov NK, Martinov MN, Johnson DA, Johnson JA. (2012). Discovery of potent, novel Nrf2 inducers via quantum modeling, virtual screening and in vitro experimental validation. Chemical Biology and Drug Design, 80(6):810-20.
  • Williamson TP, Johnson DA, Johnson JA. (2012). Activation of the Nrf2-ARE pathway by siRNA knockdown of Keap1 reduces oxidative stress and provides partial protection from MPTP-mediated neurotoxicity. Neurotoxicology, 33(3):272-9.

Mentor to METC Graduate Students:

  • Marcus Calkins (2008).
  • Jong-Min Lee (2003)

Mentor to METC Post-Doc:

  • Neal Burton (2008-2010).
  • Jon Kern (2004).
  • Julie Kern (2004)