Jeffrey A. Johnson, PhD
Position title: Professor, Pharmaceutical Sciences
- 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
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. Transplantation 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).
- Vargas MR., Johnson DA, Johnson JA. (2011). Decreased glutathione accelerates neurological deficit and mitochondrial pathology in familial ALS-linked hSOD1G93A mice model.Neurobiol. Dis. 43(3):543-51.
- Calkins M, Vargas MR, Johnson DA, Johnson JA. (2010). Astrocyte specific overexpression of Nrf2 protects striatial neurons from mitochondrial complex II inhibition. Toxicol Sci. 115(2):557-68.
- Johnson DA, Amirahmadi S, Ward C, Fabry Z, Johnson JA. (2010). The Absence of the Pro-Antioxidant Transcription Factor Nrf2 Exacerbates Experimental Autoimmune Encephalomyelitis. Toxicol. Sci. 114(2), 237–246.
- 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):4135-430.
- 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.