Michael A. Johnson
Assistant Professor
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1251 Wescoe Hall Drive Phone: (785) 864-4269 Fax: (785) 864-5396 Email: johnsonm@ku.edu |
Academic Degrees
- B.S., 1988, United States Air Force Academy
- M.S., 2000, University of Colorado , Denver
- Ph.D., 2002, University of Virginia
- Hereditary Disease Foundation Postdoctoral Fellow, University of North Carolina at Chapel Hill, 2002-2005
Areas of Specialization
Analytical Chemistry, Bioanalytical Chemistry, and Neurochemistry
Research Interests
Mike Johnson Research Group Page
Bioanalytical chemistry; microsensor development; electrochemical detection of neurotransmitters; fluorescence microscopy; neurological disorders; oxidative stress.
Neurons communicate by the release of neurotransmitters at the pre-synaptic terminal, a process called exocytosis.Immediately following exocytosis, released neurotransmitter is actively taken back up into the neuron by transporters.A thorough investigation of neurotransmitter release and uptake requires the use of techniques having adequate sensitivity to detect the analyte of interest and sufficient temporal resolution to distinguish between the release and uptake processes.The goal of my research program is the development and application of bioanalytical techniques capable of studying this signaling process. A wide array of techniques will be employed, including fluorescence microscopy, biochemical methods, and state-of-the-art electrochemical techniques which allow for the monitoring of biogenic molecules on physiologically relevant time scales.These techniques will be used to study a variety of important problems, including neurodegeneration, oxidative stress, and mechanisms of drug action.
Huntington ’s disease.Huntington’s disease (HD) is a neurodegenerative disorder characterized by uncontrollable muscle movements and mental illness.HD patients typically die 15 to 20 years following symptom onset.We and others have recently discovered that release of dopamine, a key neurotransmitter in motor and cognitive signaling, is sharply attenuated in animal models of HD.To understand the contributions of abnormal neurotransmitter release in the debilitating motor symptoms of HD, electrochemical techniques will be applied in vivo to animal models of HD.Additionally, microscopy techniques will be applied to study tissue sections in these animal models to yield clues regarding mechanisms of altered signaling.
Oxidative Stress and Neurotransmission.A strong connection has been established between oxidative stress and many neurodegenerative disorders, including Parkinson’s disease, Alzheimer’s disease, and Lou Gehrig’s disease.We are interested in the effects of oxidative stress on neuronal function.Electrochemical and microscopy techniques will be used to characterize release and uptake processes in models of oxidative stress.
Mechanisms of Drug Action.A significant percentage of children being treated with selective serotonin reuptake inhibitors (SSRIs) have been reported to have had suicidal thoughts.This has become a topic of national interest.We are interested in fully characterizing mechanisms of action of selective SSRIs and other central nervous system-active drugs using electroanalytical techniques.
Microsensor Development. Current voltammetric techniques allow for the real-time, subsecond measurement of dopamine and other electroactive neurotransmitters.However, the measurement of many non-electroactive neuromodulators, such as GABA, remains a challenge.Therefore, we are pursuing the development and application of enzyme-based microsensors capable of measuring the release of biologically active molecules on physiologically relevant time scales.
Selected Publications
Ortiz, M. A., Kurth, B. J., Osterhaus, G. L., Johnson, M. A., “Dysregulation of Intracellular Dopamine Stores Revealed in the R6/2 Mouse Striatum,” J. Neurochem. In Press
Miller, B.R., Walker, A. G., Fowler, S. C., von Horsten, S., Riess, O., Johnson, M. A., Rebec, G. V. “Dysregulation of coordinated firing patterns in striatum of freely behaving transgenic rats that model Huntington’s disease,” Neurbiology of Disease, 2010, 37, 106-113.
Fowler S. C., Miller B. R., Gaither T. W., Johnson M. A., Rebec G. V., “Force-plate quantification of progressive behavioral deficits in the R6/2 mouse model of Huntington’s disease,” Behav. Brain Res. 2009, 24;202(1):130-7. PMID: 19447289
Kraft, J. C., Osterhaus, G. L., Ortiz, A. N., Garris, P. A., Johnson, M. A., “In Vivo Dopamine Release and Uptake Impairments in Rats Treated with 3-Nitropropionic Acid,” Neuroscience, 2009, 161(3):940-9. PMID: 19362126
Osterhaus, G. L., Selley, P., Silcio, K., Lauderdale, K., Fowler, S. C., von Horsten, S., Riess, O., Johnson, M. A. (2008) “Simultaneous microdialysis and force-plate actometer measurements obtained in transgenic Huntington’s disease model rats,” in Monitoring Molecules in Neuroscience, eds. PEM Phillips, SG Sandberg, S Ahn, and AG Phillips. University of British Columbia Press, Vancouver, BC
Oien, D. B., Osterhaus, G. L., Latif, S. A., Pinkston, J. W., Fulks, J., Johnson, M., Fowler, S. C., Moskovitz, J. “MsrA knockout mouse exhibits abnormal behavior and brain dopamine levels,” Free Rad. Biol. Med. 2008, 45(2):193-200. PMID: 18466776
Wilson, G. S., Johnson, M. A. “In-vivo electrochemistry: what can we learn about living systems?” Chem Rev. 2008, 108(7):2462-81. PMID: 18558752
Johnson, M. A., Rajan, V., Miller, C. E., and Wightman, R. M. “Dopamine Release is Severely Compromised in the R6/2 Mouse Model of Huntington’s Disease,” J. Neurochem. 2006, 97, 737-746.
Heien, M. L. A. V., Johnson, M. A., and Wightman, R. M. “Resolving Neurotransmitters Detected by Fast-scan Cyclic Voltammetry," Analytical Chemistry 2004, 76(19), 5697-5704
Johnson, M. A., Macdonald, T. L., Mannick, J. B., Conaway, M. R., and Gaston, B. “Accelerated S-Nitrosothiol Breakdown by Amyotrophic Lateral Sclerosis Mutant Copper, Zinc-Superoxide Dismutase,” J. Biol. Chem. 2001, 276, 39872-39878.
Lipton, A. J., Johnson, M. A., Macdonald, T.,Lieberman, M. W., Gozal, D., and Gaston, B. “S-Nitrosothiols Signal the Ventilatory Response to Hypoxia,” Nature 2001, 413, 171-174. Featured in News and Views.
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