This is a Senior Scientist Award application for Dr. Donald M. Kuhn. The PI is a tenured professor in the Department of Psychiatry and Behavioral Neurosciences at the Wayne State University School of Medicine, with joint appointments in the Center for Molecular Medicine and Genetics and the Institute of Chemical Toxicology. He has been active in drug abuse research related activities for more than 20 years and has made important contributions to the field in areas relating to: 1) biochemical and molecular characterization of how reactive oxygen and reactive nitrogen species modify the function of protein targets known to be damaged by the neurotoxic amphetamines (eg, monoamine transporters and monooxygenase enzymes); 2) behavioral characterization of hallucinogenic drugs of abuse using drug discrimination techniques; and 3) regulation of the neurochemical function of monoamine neurons. Dr. Kuhn currently devotes 40-50 percent of his time to research and mentoring activities while 50-60 percent of his effort is dedicated to teaching, departmental, and college responsibilities. This Senior Scientist Award will allow him to increase his research effort to approximately 80 percent. The increase in research time will allow Dr. Kuhn the opportunity to develop expertise in and apply new technologies to his research program including the creation of genetic switch (conditional) knock-out mice through homologous recombination, the use of mass spectrometry in characterizing how drugs of abuse modify key proteins in brain, and the application of functional genomics (i.e., microarray analysis) and proteomics to the evaluation of neuronal gene and protein expression patterns related to specific drugs of abuse. In addition, as the PI of a NIDA-funded T32, and as the mentor of graduate students and postdoctoral fellows with NIDA funded F31/32s in his lab, Dr. Kuhn will remain extensively engaged in scientific mentoring activities.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Award (K05)
Project #
5K05DA014692-03
Application #
6797945
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Frankenheim, Jerry
Project Start
2002-09-30
Project End
2007-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
3
Fiscal Year
2004
Total Cost
$120,236
Indirect Cost
Name
Wayne State University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
001962224
City
Detroit
State
MI
Country
United States
Zip Code
48202
Kuhn, Donald M; Angoa-PĂ©rez, Mariana; Thomas, David M (2011) Nucleus accumbens invulnerability to methamphetamine neurotoxicity. ILAR J 52:352-65
Kuhn, Donald M; Francescutti-Verbeem, Dina M; Thomas, David M (2008) Dopamine disposition in the presynaptic process regulates the severity of methamphetamine-induced neurotoxicity. Ann N Y Acad Sci 1139:118-26
Thomas, David M; Francescutti-Verbeem, Dina M; Kuhn, Donald M (2008) Methamphetamine-induced neurotoxicity and microglial activation are not mediated by fractalkine receptor signaling. J Neurochem 106:696-705
Thomas, David M; Francescutti-Verbeem, Dina M; Kuhn, Donald M (2008) The newly synthesized pool of dopamine determines the severity of methamphetamine-induced neurotoxicity. J Neurochem 105:605-16
Thomas, David M; Francescutti-Verbeem, Dina M; Kuhn, Donald M (2006) Gene expression profile of activated microglia under conditions associated with dopamine neuronal damage. FASEB J 20:515-7
Thomas, David M; Kuhn, Donald M (2005) Attenuated microglial activation mediates tolerance to the neurotoxic effects of methamphetamine. J Neurochem 92:790-7
Thomas, David M; Kuhn, Donald M (2005) MK-801 and dextromethorphan block microglial activation and protect against methamphetamine-induced neurotoxicity. Brain Res 1050:190-8
Kuhn, Donald M; Sakowski, Stacey A; Sadidi, Mahdieh et al. (2004) Nitrotyrosine as a marker for peroxynitrite-induced neurotoxicity: the beginning or the end of the end of dopamine neurons? J Neurochem 89:529-36
Thomas, David M; Francescutti-Verbeem, Dina M; Liu, Xiuli et al. (2004) Identification of differentially regulated transcripts in mouse striatum following methamphetamine treatment--an oligonucleotide microarray approach. J Neurochem 88:380-93
Park, Samuel; Geddes, Timothy J; Javitch, Jonathan A et al. (2003) Dopamine prevents nitration of tyrosine hydroxylase by peroxynitrite and nitrogen dioxide: is nitrotyrosine formation an early step in dopamine neuronal damage? J Biol Chem 278:28736-42

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