Recruitment of in Vivo Neuropharmacologist to Support CNS Drug Discovery Research

描述(由申请人提供)：范德比尔特药物发现计划(VPDD)是一项世界级的努力，完全专注于发现和表征新的分子，以评估治疗中枢神经系统疾病的新的潜在治疗策略。VPDD在发现中枢神经递质受体、离子通道和其他信号蛋白的多个配体方面取得了巨大的成功。这为理解操纵这些信号通路对动物行为的影响以及作用于这些系统的药物的潜在治疗作用提供了一个令人兴奋的机会，实现了前所未有的进展。然而，至关重要的是，在使用新分子进行体内研究之前，从这项研究和类似的学术药物发现工作中产生的分子必须在药代动力学特性和脑渗透方面得到充分表征。因此，在体内研究新发现的化合物的神经药理学家必须将药物处置的研究无缝地纳入他们的工作中。VPDD已经建立了最先进的动物给药、血浆和脑脊液收集以及在动物模型中进行新化合物详细药代动力学研究所需的分析化学设施。此外，VPDD和范德比尔特分子神经科学中心(CMN)都建立了出色的设施，用于啮齿动物模型的行为和其他活体研究。这提供了超越细胞和分子研究的机会，这些研究推动了目前许多VPDD的努力，并专注于获得对操纵特定神经递质系统和信号通路的体内影响的新见解。然而，为了利用这一独特的机会，招聘具有强大的体内药理学专业知识并具有将行为药理学与药物处置和新化合物的中枢神经系统暴露研究相结合所需技能的教职员工将是至关重要的。我们现在通过NIH寻求资金，以支持招聘一位杰出的活体神经药理学家到VPDD和药理学系的终身教职跟踪职位，我们向新招聘的教师提出一个强有力的发展方案，并提供一个明确的计划，与新招聘的教师合作，通过教师指导、合作研究机会和其他必要的支持，使新招聘的教师能够在神经药理学领域建立独立的职业生涯和领导地位。 公共卫生相关性：我们建议招聘一名杰出的体内神经药理学家，担任范德比尔特药物发现计划和范德比尔特药理学系终身教职。在VPDD的背景下工作，为体内神经药理学家在理解操纵特定信号通路对动物行为的影响以及作用于这些系统的药物的潜在治疗效用方面取得前所未有的进展提供了一个独特的机会。利用这笔赠款的支持，我们将提供强大的发展包、有重点的教师指导、合作研究机会和其他所需的支持，以帮助新招聘人员在神经药理学领域建立独立的职业生涯和领导地位。

DESCRIPTION (provided by applicant): The Vanderbilt Program in Drug Discovery (VPDD) is a world class effort fully focused on discovery and characterization of novel molecules to evaluate new potential treatment strategies for CNS disorders. The VPDD has had tremendous success in discovery of multiple ligands for CNS neurotransmitter receptors, ion channels, and other signaling proteins. This provides an exciting opportunity to realize unprecedented advances in understanding of the impact of manipulating these signaling pathways on animal behavior and the potential therapeutic utility of drugs acting on these systems. However, it is critical that molecules generated from this and similar academic drug discovery efforts are fully characterized in terms of pharmacokinetic properties and brain penetration before using novel molecules for in vivo studies. Thus, in vivo neuropharmacologists working with newly discovered compounds must seamlessly incorporate studies of drug disposition into their work. VPDD has established state of the art facilities for animal dosing, plasma and csf collection, and analytical chemistry required for detailed pharmacokinetic studies of novel compounds in animal models. In addition both the VPDD and Vanderbilt's Center for Molecular Neuroscience (CMN) have established outstanding facilities for use in behavioral and other in vivo studies in rodent models. This provides the opportunity to move beyond cellular and molecular studies that drive many of the current VPDD efforts and focus on gaining new insights into in vivo effects of manipulating specific neurotransmitter systems and signaling pathways. However, to take advantage of this unique opportunity, it will be critical to recruit faculty who have strong in vivo pharmacology expertise and who have the skills required to combine behavioral pharmacology with studies of drug disposition and CNS exposure of novel compounds. We now seek funding through the NIH to support recruitment of an outstanding in vivo neuropharmacologist to a tenure track faculty position in VPDD and Department of Pharmacology, we propose a strong development package to the new faculty recruit and provide a clear plan to work with new recruit to through faculty mentoring, collaborative research opportunities, and other support needed to allow the new recruit to establish an independent career and leadership position in neuropharmacology. PUBLIC HEALTH RELEVANCE: We propose recruitment of an outstanding in vivo neuropharmacologist to a tenure track faculty position in the Vanderbilt Program in Drug Discovery and the Vanderbilt Department of Pharmacology. Working within the context of the VPDD, provides a unique opportunity for an in vivo neuropharmacologist to achieve unprecedented advances in understanding of the impact of manipulating specific signaling pathways on animal behavior and the potential therapeutic utility of drugs acting on these systems. Using support from this grant, we will provide strong development package, focused faculty mentoring, collaborative research opportunities, and other support needed to help the new recruit to establish an independent career and leadership position in neuropharmacology.