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Jeffrey
Johnson, Ph.D.
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- Trainer in the Following
Programs:
- Molecular and Environmental
Toxicology Program
- Neuroscience Program
- Pharmaceutical Sciences
Program
- Molecular and Cellular Pharmacology
- Cellular and Molecular Biology
- Medical Sciences Training
Program
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Honors and Awards:
- 1997-01 Burroughs Wellcome
Fund New Investigator in Toxicological Sciences
- 1994-96 NIH National Research
Service Award
- 1993-94 NIH Molecular Neuroscience
Postdoctoral Trainee
- 1992 Alvin L. Berman and
Ruth Bleier Memorial Research Award for research excellence in the study
of human development and developmental disabilities.
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Research Description:
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 by the pathology of Alzheimer's
Disease, presumably due to increased oxidative stress caused by ß-amyloid.
We know, therefore, the driving force for the development of Alzheimer's
Disease; however, we have little knowledge of how the different genes
and proteins contributing to antioxidant defenses are regulated in brain.
My laboratories goal is to discover ways to increase the defense mechanisms
in brain by activating multiple antioxidant defense genes simultaneously.
A process we refer to a 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) the molecular mechanism(s) by which tert-butylhydroquinone
(tBHQ) activate the antioxidant responsive element (ARE)-driven genes
in neuroblastoma cells, primary neuronal and glial cultures, and in vivo
through the use of transgenic reporter mice; 2) how ARE-driven genes block
apoptosis; 3) the effect of overexpression of amyloid precursor protein
(APP) on the ARE and antioxidant genes in neurons and glia using oligonucleotide
microarrays; and 4) the regulation of ARE-driven genes in human neural
stem cells using oligonucleotide microarrays. In addition to the Alzheimer’s
mice, we are presently studying transgenic animal models for Amyotrophic
Lateral Sclerosis, Huntington’s Disease and Autoimmune Disease. |
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Wisconsin State Journal Mention:
Selected Publications: Articles on PubMed
- Kraft AD, Resch JM, Johnson DA, and Johnson JA. (2007). Activation of the Nrf2-ARE pathway in muscle and spinal cord during ALS-like pathology in mice expressing mutant SOD1. Exp Neurol. 207:107-117. PMID 17631292
- Kraft AD, Lee JM, Johnson
DA, Kan YW, Johnson JA. (2006). Neuronal sensitivity to kainic acid is
dependent on the Nrf2-mediated actions of the antioxidant response element.
J Neurochem. 98:1852-65. PDF PMID 16945104
- Hagemann TL, Gaeta SA, Smith
MA, Johnson DA, Johnson JA, Messing A. (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. 14:2443-58. PDF PMID 16014634
View More Publications
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