New Horizons in Adult Neurogenesis

描述(申请人提供)：这是一份NIDA独立科学家奖(K02)的申请书。这位候选人名叫阿米莉亚·J·艾施，是达拉斯德克萨斯大学西南医学中心精神病学系六年级的助理教授。在她的整个职业生涯中，Eisch博士建立了良好的发表记录(总共39篇，17篇来自她的独立实验室)，奖项和资金来自联邦(4篇来自NIDA，1篇来自NIA，1篇来自NIMH，1篇来自NSF)和非联邦来源(2篇来自NARSAD，2篇来自Stanley Foundation)，以及指导。自2000年加入德克萨斯大学西南学院以来，艾施博士制定了一项独特的研究计划，专注于了解滥用药物对海马体，特别是对成年海马神经发生的潜在负面影响的潜在机制。然而，越来越多的行政和教学责任阻碍了艾施博士的研究进展，以至于她只能将50%的时间投入到研究中。K02奖的获得将取消或限制这些义务，从而允许Eisch博士(1)推进她关于鸦片类药物对成人海马神经发生的影响的工作；(2)培养关于CDK5在成人海马神经发生中的作用的新开发的合作；(3)从UT Southwest的同事那里学习尖端技术(荧光激活细胞分类、微阵列分析、激光捕获显微解剖、逆转录病毒生产以及生化和神经球分析)的原理和实践，并将其应用于她的研究；(4)利用她新开发的Nestin-CreER12小鼠模型，最大限度地阐明滥用药物对海马体结构的影响；(5)为一系列拨款申请生成足够的数据，以及准备这些申请的时间：(1)为她现有的R01提出竞争性续签申请，1项新的NIDA R01申请，以及1项额外的小额或探索性拨款申请，也包括NIDA；(5)花更多时间指导她实验室的6名研究生和2名博士后研究员；以及(6)与成瘾领域内外的合作者合作，研究滥用药物诱导的海马神经可塑性。K02奖提供的稳定性和保护时间最终将支持两个新项目，该项目探索滥用药物、成人神经干细胞和这些细胞增殖所在的海马体环境之间的复杂关系。因此，这些研究具有巨大的潜力，可以提高我们对滥用药物影响大脑功能的复杂机制的理解，从而可能为治疗成瘾和复吸药物开辟新的途径。这些研究还将揭示成人神经干细胞如何适应长期接触滥用药物的问题，因此对于未来利用神经干细胞修复受伤的、甚至上瘾的大脑的努力将是重要的。

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.