Molecular Neurobiology of Drug Abuse

描述：(申请人提供) 这是唐纳德·M·库恩博士的高级科学家奖申请书。圆周率是 精神病学和行为学系终身教授 韦恩州立大学医学院神经科学，联合 分子医学和遗传学中心的任命以及 化学毒理研究所。他一直活跃在药物滥用研究中 从事相关活动20多年，做出了重要贡献 涉及以下领域：1)生物化学和分子 活性氧和活性氮物种如何修饰的表征 已知的被神经毒素损伤的蛋白质靶标的功能 苯丙胺(如单胺转运体和单加氧酶)；2) 吸毒致幻药物滥用的行为特征 辨别技术；3)神经化学功能的调节。 单胺类神经元。库恩博士目前将40%-50%的时间用于 研究和指导活动，而他50%-60%的精力是 致力于教学、院系和学院的职责。这位前辈 科学家奖将使他的研究努力增加到大约 80%。研究时间的增加将使库恩博士有机会 在他的研究计划中发展专业知识并应用新技术 包括通过创造遗传开关(条件)基因敲除小鼠 同源重组，使用质谱学来表征如何 滥用药物改变大脑中的关键蛋白质，以及功能性药物的应用 基因组学(即微阵列分析)和蛋白质组学对 与特定药物相关的神经元基因和蛋白表达谱 虐待。此外，作为NIDA资助的T32的PI，以及 研究生和博士后研究员在他的实验室里用NIDA资助的F31/32， 库恩博士将继续广泛参与科学指导活动。

DESCRIPTION: (provided by the applicant) 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.