Clinical Neuroendocrinology of Leptin

描述：(申请人提供)：这份申请提出了一个严格的 以病人为中心的研究和指导计划。私家侦探是西班牙裔 医生-调查员，在基于数据的， 以假设为导向，以病人为导向的调查和指导。担任署长 加州大学洛杉矶分校翻译调查研究生培训项目 加州大学洛杉矶分校GCRC项目主任，两家自然出版集团期刊的编辑， 分子精神病学和药物基因组学杂志，P.I.是唯一的 有资格提供临床研究培训并指导年轻的临床医生 调查人员。这一奖项将支持他开发新的导师的努力 项目既包括私家侦探S自己的研究领域，也包括 临床研究。这包括基本技能方面的指导， 受过良好训练的人所需的方法、理论和概念化 独立的临床研究人员。具体地说，私家侦探将指导年轻的 研究人员在设计临床研究项目、假设 发展，临床药理学和药物基因组学，科学写作， 以及与临床研究相关的法律、伦理和监管问题。 与研究特别相关并普遍感兴趣的问题 那些处于职业生涯早期阶段的人包括少数群体的培训 临床研究人员与种族认同研究的开展 少数族裔人口。这项研究提案验证了瘦素 有助于调节人体神经内分泌功能的动态变化。 这一假设将通过精心设计的前瞻性临床试验进行验证。 高血压病患者内分泌节律的快速采样动态研究 瘦素替代治疗在仅有的三名成年个体中得到证实 由于功能性瘦素基因突变而导致瘦素天真的FAR患者。我们会 研究他们在基线和瘦素治疗过程中的内分泌功能 治疗，并将其与不缺乏瘦素的肥胖者进行比较。这个 私家侦探此前曾与这些患者合作过。他们是一个大型、 延长的，高度血缘关系的谱系，病态肥胖，并存在 内分泌功能障碍。来检验瘦素对 人类神经内分泌功能的动力学，我们提出了一系列前瞻性的， 瘦素治疗过程中的纵向、快速采样、24小时内分泌研究 这些患者的替代治疗和三个种族定义的对照 组。我们的假设得到证实可能会产生两种后果。对于 对生物学的理解，它将表明瘦素有助于调节 中枢神经系统的一项关键功能，即神经内分泌 动态平衡。这项工作可能会揭示瘦素潜在的新作用部位。 治疗价值。

DESCRIPTION: (provided by applicant): This application presents a rigorous program of patient-oriented research and mentoring. The P.I. is a Hispanic physician-investigator with a substantial track record in data-based, hypothesis-driven patient-oriented investigation and mentoring. As Director of the UCLA Graduate Training Program in Translational Investigation, Associate UCLA GCRC Program Director, and Editor of two Nature Publishing Group journals, Molecular Psychiatry and The Pharmacogenomics Journal, the P.I. is uniquely qualified to provide clinical research training and to mentor young clinical investigators. This award would support his efforts to develop new mentoring programs both in the P.I. 's own area of research and in the core components of clinical research. This includes mentoring in the fundamental skills, methodology, theories, and conceptualizations necessary for the well-trained, independent, clinical researcher. Specifically, the P.I. will mentor young investigators in the design of clinical research projects, hypothesis development, clinical pharmacology and pharmacogenomics, scientific writing, and the legal, ethical and regulatory issues related to clinical research. Issues that are particularly relevant to research and of general interest to those in the early stages of their careers include the training of minority clinical researchers and the conduction of research in ethnically identified minority populations. The research proposal tests the hypothesis that leptin contributes to the regulation of the dynamics of human neuroendocrine function. This hypothesis will be tested by a carefully designed, prospective clinical study of the rapidly-sampled dynamics of endocrine rhythms during the course of leptin-replacement treatment in the only three adult individuals identified so far who are leptin-naive due to a functional leptin gene mutation. We will study their endocrine function at baseline, and during the course of leptin treatment, and compare it to obese subjects who are not leptin deficient. The P.I. has previously worked with those patients. They are member of a large, extended, highly consanguineous pedigree, are morbidly obese, and present with endocrine dysfunction. To test the hypothesis that leptin impacts on the dynamics of human neuroendocrine function, we propose a series of prospective, longitudinal, rapid-sampled, 24-h endocrine studies during the course of leptin replacement therapy in those patients and in three ethnically-defined control groups. The confirmation of our hypothesis may have two consequences. For the understanding of biology, it will indicate that leptin contributes to regulate a key function of the central nervous system, which is neuroendocrine homeostasis. This work may reveal new sites of leptin action with potential therapeutic value.