K02 Application

描述（由申请人提供）： 这是一个职业发展奖的建议博士安妮特Fleckenstein。她是犹他州大学药理学和毒理学副教授。她在药物滥用研究领域活跃了10年，并在阐明精神兴奋剂对多巴胺（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，特别是与安非他明的神经毒性作用有关。申请人目前将50%的时间用于研究，而50%的精力用于教学，部门和学院活动。该职业发展奖将使申请人的研究工作增加到75%;大大增加了她的研究灵活性，并使她能够充分利用她的科学技能，因为她成为她的学术领域的领导者。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）METH和可卡因对VMAT-2和DAT影响的差异有助于其独特的持续DA后果; 2）哌甲酯影响囊泡DA转运和VMAT-2的神经元内定位，其方式与安非他明不同。从职业发展奖导致的研究时间的增加不仅使申请人能够扩大这些研究，而且还开发新的技术专业知识，她的实验室，包括液相色谱-质谱法，以探索的假设，甲基诱导差异修饰的DAT低聚物的形成。研究时间的增加也将使申请人有更多的机会参与跨学科的努力，如涉及犹他州成瘾中心（翻译中心）。

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).