Dynorphins and Kappa Opioid Receptors in the Stress Response

描述(由申请人提供)：这是第一次申请续期，要求第二次为期5年的高级科学家研究和导师奖(K05)的支持。目前的奖项对我作为一名科学领导者和导师的职业发展非常重要，因为它让我能够将精力集中在这些责任上。在此期间，我的科学领导工作包括指导威斯康星州药物成瘾研究中心，开发核心行为、成像和蛋白质组研究设施，促进科学合作，并促进社区外展。我的校外领导包括于2011年7月组织了一次关于“卡帕阿片类药物在疼痛和成瘾中的治疗潜力”的科学会议，并在国际麻醉品研究会议(INRC)的执行委员会服务。目前的K05奖使我能够将精力集中在研究进展上，并在过去4年多的时间里发表了28篇同行评议的出版物，纳入了新的方法，产生了新的见解，并提出了新的假设。目前的资助期支持了我的导师活动的扩大，包括更新NIDA T32“滥用药物的分子药理学培训”和授予ARRA-NIDA P30“寻找治疗药物滥用的功能蛋白质组学方法的新教师”，这两项活动都是我领导的。K05、P30和T32奖项鼓励我积极参与“生物医学研究诚信培训计划”，并使我能够积极指导研究生和本科生、博士后研究员和新教师。下一期的K05支持将建立在此基础上，将我的时间从额外的服务教学和管理责任中解放出来，并允许我将我的努力致力于三个研究目标：第一，测试c-Jun Kinase的阿片受体激活提供了一种新的GPCR信号调节机制的假设。第二，p38MAPK的kappa阿片受体激活启动了导致应激焦虑和焦虑效应的信号事件。第三，在下一个支持阶段，K05将使我的实验室在蛋白质分析化学技术方面获得优势，这是确定阿片受体信号复合体成分所必需的。在目前的资助期间，我指导了3名进入教职的博士后研究员(Brucha，Macey&Gendron)；2名建立了成功的研究项目并获得晋升的初级教员(Phillips和Stella)；以及3名获得博士学位并晋升为博士后研究员职位的研究生。在接下来的资助期间，我希望积极促进两名新的终身教职跟踪助理教授(Zwiefel和Ong)、5名研究生和3名博士后研究员的专业发展。

DESCRIPTION (provided by applicant): This is a first renewal application requesting a second 5-yr period of support of a Senior Scientist Research and Mentorship Award (K05). The current award has been extremely important for my professional development as a scientific leader and mentor by allowing me to focus my effort on those responsibilities. My scientific leadership efforts during this period include direction of a UW Center for Drug Addiction Research, developing core behavioral, imaging and proteomic research facilities, fostering scientific collaborations, and promoting community outreach. My extramural leadership includes organization of a scientific conference scheduled in July 2011 on the "Therapeutic Potential of Kappa Opioids in Pain and Addiction" and service on the executive committees of the International Narcotics Research Conference (INRC). The current K05 award has enabled me to focus my effort on research progress and has resulted in 28 peer-reviewed publications during the last 4+ years that incorporated new approaches, generated new insights, and developed novel hypotheses. The current funding period has supported an expansion of my mentorship activities including the renewal of a NIDA T32 "Training in Molecular Pharmacology of Abused Drugs" and the award of an ARRA-NIDA P30 "New Faculty Search For Functional Proteomic Approaches To Drug Abuse," both of which I direct. The K05, P30 and T32 awards have encouraged my active participation in a "Biomedical Research Integrity Training Program" and enabled active mentoring of graduate and undergraduate students, postdoctoral fellows, and new faculty. The next period of K05 support would build on this foundation by protecting my time from extra service-teaching and administrative responsibilities and allowing me to devote my efforts towards 3 research goals: First, to test the hypothesis that opioid receptor activation of c-Jun Kinase provides a novel mechanism of GPCR signal regulation. Second, that kappa opioid receptor activation of p38 MAPK initiates signaling events responsible for the dysphoric and anxiogenic effects of stress. And third, in the next period of support, the K05 would enable my lab to gain strength in protein analytical chemistry techniques necessary to define components of the opioid receptor signaling complex. In the current funding period, I have mentored 3 postdoctoral fellows who have gone on to faculty positions (Bruchas, Macey & Gendron); 2 junior faculty members who have built successful research programs and earned promotion (Phillips and Stella); and 3 graduate students who earned their doctorates and advanced to postdoctoral fellowship positions. In the next funding period, I expect to actively promote the professional development of two new tenure-track assistant professors (Zwiefel and Ong), 5 graduate students & 3 postdoctoral fellows currently working in the lab.