New Horizons in Adult Neurogenesis

描述（由申请人提供）：这是NIDA独立科学家奖（K02）的申请。候选人Amelia J. Eisch博士是达拉斯德州大学西南医学中心精神病学系的助理教授，今年是她的第六年。在她的职业生涯中，Eisch博士建立了良好的出版物记录（总共39篇，其中17篇来自她的独立实验室），来自联邦（NIDA 4篇，NIA 1篇，NIMH 1篇，NSF 1篇）和非联邦（NARSAD 2篇，Stanley Foundation 2篇）的奖励和资助，以及指导。自2000年加入UT西南学院以来，Eisch博士开发了一个独特的研究项目，重点是了解药物滥用对海马体，特别是成人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责任阻碍了Eisch博士的研究进展，以至于她只能将50%的时间用于研究。获得K02奖将消除或限制这些义务，从而允许Eisch博士(1)推进她在阿片类药物对成人海马神经发生的影响方面的工作；(2)培养一项关于Cdk5在成人海马神经发生中的作用的新合作；(3)学习UT Southwestern同事的前沿技术（荧光活化细胞分选、微阵列分析、激光捕获显微解剖、逆转录病毒生产、生化和神经球测定）的原理和实践，并将其应用于研究；(4)利用她新建立的巢蛋白- creer12小鼠模型，最大限度地阐明药物滥用对海马结构的影响；(5)为一系列拨款申请提供足够的数据，并为其准备时间：对其现有的R01进行竞争性续期申请，新的NIDA R01申请，以及向NIDA提交的额外的小型或探索性拨款申请；(5)增加对实验室6名研究生和2名博士后的指导和互动时间；(6)结合成瘾领域内外的合作伙伴，开展药物滥用诱导海马神经可塑性的研究。K02奖提供的稳定性和保护时间最终将支持两个探索滥用药物、成体神经干细胞和这些细胞增殖的海马体环境之间复杂关系的新项目。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，因此可能为药物成瘾和复发的治疗开辟新的途径。这些研究还将揭示成人神经干细胞如何适应长期滥用药物的情况，因此对未来利用神经干细胞修复受伤甚至成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.