New Horizons in Adult Neurogenesis

描述（由申请人提供）：这是NIDA独立科学家奖（K 02）的申请。这位候选人是阿米莉亚·J·普莱希博士，是一个助理教授在她的第六年精神病学系在德州西南医学中心在达拉斯。在她的整个职业生涯中，Dr. Reich已经建立了一个强大的出版物记录（共39篇; 17篇来自她的独立实验室），来自联邦（4篇来自NIDA，1篇来自NIA，1篇来自NIMH，1篇来自NSF）和非联邦（2篇来自NARSAD，2篇来自斯坦利基金会）来源的奖项和资金，以及指导。自2000年加入UT西南学院以来，Dr. Edich博士开发了一个独特的研究项目，重点是了解滥用药物对海马体，特别是成年海马体神经发生的潜在负面影响的机制。然而，越来越多的行政和教学工作阻碍了Dr. Edich的研究进展，以至于她只能将50%的时间用于研究。K 02奖的获得将消除或限制这些义务，从而使Dr. Edich（1）推进她关于阿片类药物对成人海马神经发生的影响的工作;（2）培养新开发的关于Cdk 5在成人海马神经发生中的作用的合作;（3）学习前沿技术的原理和实践（荧光激活细胞分选，微阵列分析，激光捕获显微切割，逆转录病毒生产，以及生物化学和神经球测定），并将其应用于她的研究;（4）使用她新开发的nestin-CreER 12小鼠模型，以最大限度地发挥其阐明滥用药物对海马结构的影响的潜力;（5）为一系列资助申请产生足够的数据，并有时间准备它们：她现有R 01的竞争性更新申请，新的NIDA R 01申请，以及额外的小额或探索性资助申请，也是NIDA;（5）花更多时间指导她实验室的六名研究生和两名博士后研究员，并与他们交流;（6）邀请成瘾领域内外的合作者参与滥用药物引起的海马神经可塑性研究。该K 02奖项提供的稳定性和保护时间最终将支持两个新项目，探索滥用药物，成人神经干细胞和这些细胞增殖的海马环境之间的复杂关系。因此，这些研究具有很大的潜力，可以提高我们对药物滥用影响大脑功能的复杂机制的理解，因此可能为治疗成瘾和复吸开辟新的途径。这些研究还将揭示成人神经干细胞如何适应长期暴露于滥用药物的迫切需要，因此对于未来利用神经干细胞修复受伤甚至成瘾的大脑的努力将非常重要。

DESCRIPTION (provided by applicant): This is an application for a NIDA Independent Scientist Award (K02). The candidate, Amelia J. Eisch, Ph.D., is an Assistant Professor in her sixth year on the psychiatry faculty at UT Southwestern Medical Center in Dallas. Throughout her career, Dr. Eisch has established a strong record of publications (39 total; 17 from her independent laboratory), awards and funding from both federal (4 from NIDA, 1 from NIA, 1 from NIMH, 1 from NSF) and non-federal (2 from NARSAD, 2 from Stanley Foundation) sources, and mentoring. Since joining the UT Southwestern faculty in 2000, Dr. Eisch has developed a unique research program with a focus on understanding mechanisms underlying the potent negative impact of drugs of abuse on the hippocampus, particularly on adult hippocampal neurogenesis. However, increasing administrative and teaching obligations have hampered Dr. Eisch's research progress, such that she is able to only devote 50% of her time on research. The receipt of a K02 award would remove or restrict these obligations, thus allowing Dr. Eisch (1) to advance her work on the impact of opiates on adult hippocampal neurogenesis; (2) to nurture a newly-developed collaboration on the role of Cdk5 in adult hippocampal neurogenesis; (3) to learn the principals and practice of cutting-edge techniques (fluorescent activated cell sorting, microarray analysis, laser capture microdissection, retrovirus production, and biochemical and neurosphere assays) from UT Southwestern colleagues, and apply them to her research; (4) to use her newly-developed nestin-CreER12 mouse model to its maximum potential for elucidating the impact of drugs of abuse on hippocampal structure; (5) to generate sufficient data for a series of grant applications, and the time to prepare them: a competitive renewal application for her existing R01, a new NIDA R01 application, and an additional small or exploratory grant application, also to NIDA; (5) to spend more time mentoring and interacting with the six graduate students and two postdoctoral fellows in her laboratory; and (6) to engage collaborators from both inside and outside the addiction field in research on hippocampal neuroplasticity induced by drugs of abuse. The stability and protected time offered by this K02 award would ultimately support two new projects exploring the complex relationship between drugs of abuse, adult neural stem cells, and the hippocampal environment in which these cells proliferate. As such, these studies hold great potential to improve our understanding of the complex mechanisms by which drugs of abuse affect brain function, and therefore may open new avenues for treatment of addiction and relapse to drug seeking. These studies will also shed much-needed light on how adult neural stem cells adapt to chronic exposure of a drug of abuse, and thus will be important to future efforts to harness neural stem cells for repair of the injured, even addicted, brain.