K02 Application

描述(由申请人提供)： 这是给Annette Fleckenstein博士的职业发展奖建议。她是犹他大学的药理学和毒理学副教授。她从事药物滥用研究已有10年，并在阐明精神刺激剂对多巴胺(DA)转运体(DAT)和囊泡单胺转运体-2(VMAT-2)调节和功能的影响方面做出了重要贡献，特别是与苯丙胺的神经毒性作用有关。申请者目前50%的时间用于研究，50%的时间用于教学、系和大学活动。这项职业发展奖将允许申请者将她的研究努力增加到75%；大大增加了她的研究灵活性，并允许她在成为学术领域的领导者时充分利用她的科学技能。在获得该奖项的支持期间，她将指导测试以下主要假设的研究：1)冰毒和可卡因对VMAT-2和DAT的影响差异有助于其独特的持续性DA后果；以及2)哌醋甲酯以不同于苯丙胺的方式影响囊泡DA运输和VMAT-2的神经元内定位。职业发展奖带来的研究时间的增加不仅使申请者能够扩展这些研究，还将发展她的实验室新技术方面的专业知识，包括探索冰毒诱导形成差异修饰的DAT寡聚体的假设的液体色谱-质谱仪。研究时间的增加也将使申请者有更多的机会参与跨学科的努力，例如涉及犹他州成瘾中心(一家翻译中心)的努力。

DESCRIPTION (provided by applicant): This is a Career Development Award proposal for Dr. Annette Fleckenstein. She is an Associate Professor of Pharmacology and Toxicology at the University of Utah. She has been active in drug abuse research for 10 years and has made important contributions to elucidating the effects of psychostimulants on dopamine (DA) transporter (DAT) and vesicular monoamine transporter-2 (VMAT-2) regulation and function, especially as related to the neurotoxic effects of the amphetamines. The applicant currently devotes 50% of her time to research while 50% of her effort is occupied by teaching, department, and college activities. This Career Development Award will allow the applicant to increase her research effort to 75%; substantially increasing her research flexibility and allow her to fully take advantage of her scientific skills as she becomes established as a leader in her academic field. During the time of support by this award, she will direct research which tests the following principal hypotheses: 1) differences in the effect of METH and cocaine on VMAT-2 and DAT contribute to their unique persistent DA consequences; and 2) methylphenidate affects vesicular DA transport and the intraneuronal localization of VMAT-2 in a manner distinct from amphetamine. The increase in research time resulting from a Career Development Award will not only allow the applicant to expand upon these studies, but also develop expertise in technologies new to her laboratory, including liquid chromatography-mass spectrometry to explore the hypothesis that METH-induces formation of differentially modified DAT oligomers. The increase in research time will also allow the applicant greater opportunity to participated in interdisciplinary efforts such as those involving the Utah Addiction Center (a translational center).