Post-translational Regulation of Opioid Receptors

描述（由申请人提供）：候选人Lakshmi Devi博士是西奈山医学院药理学系统治疗学系的教授。她目前由两个独立的赠款资助：来自NIDA/NIH的DA 08863-研究阿片受体的翻译后调节和来自NINDS/NIH的NS 26880-研究神经肽生物合成的调节。候选人的长期职业目标是探索阿片受体特征对药物成瘾发展的贡献，并确定参与这一过程的分子和途径，旨在开发药理学工具，以帮助预防和/或治疗药物滥用。西奈山医学院为实现这一目标所需的协同和协作互动提供了智力环境。高级科学家研究和导师奖将通过减轻大量的教学和行政工作来促进这一点。Devi博士实验室的研究重点是探索调节阿片受体功能的分子机制。阿片受体的活性受多种机制调节。例如，活性在受体本身的水平以及内源性肽（其激活受体）的水平上调节。近年来，候选人的研究集中在这两种机制上。本研究旨在进一步探讨这两种机制。具体目标是：（i）研究体内吗啡给药对5-4受体的信号传导、成熟和调节;（ii）研究阿片受体和其他七螺旋受体之间异二聚化的作用;（iii）探索最近鉴定的非经典加工酶在阿片和其他神经肽水平调节中的生理参与。本资助申请中描述的研究将提供有关调节阿片受体功能的早期事件的关键信息。阐明参与受体功能调节的细胞通路是确定药物成瘾的适当药理学干预的一个令人信服的策略。该奖项将允许候选人专注于阿片肽及其受体领域的研究。此外，该奖项将帮助指导下一代有兴趣探索新机制和确定药物滥用障碍治疗新靶点的研究人员。

DESCRIPTION (provided by applicant): The candidate, Dr. Lakshmi Devi is a Professor in the Department of Pharmacology Systems Therapeutics, Mount Sinai School of Medicine. She is currently funded by two independent grants: DA 08863 from NIDA/NIH- to study post-translational regulation of opioid receptors and NS 26880 from NINDS/NIH-to study regulation of neuropeptide biosynthesis. The long-term career goals of the candidate are to explore the contribution of opioid receptor characteristics to development of drug addiction and to identify molecules and pathways involved in this process with the intent of developing pharmacological tools to help in the prevention and/or treatment of drug abuse. Mount Sinai School of Medicine provides the intellectual environment for synergistic and collaborative interactions necessary to achieve this goal. The Senior Scientist Research and Mentorship Award will facilitate this by relieving considerable amount of teaching and administrative duties. The focus of studies in Dr. Devi's laboratory has been to explore molecular mechanisms modulating opioid receptor function. The activity of opioid receptors is modulated by multiple mechanisms. For example, the activity is modulated at the level of the receptors themselves as well as at the level of endogenous peptides (that activate the receptors). In recent years the candidate's research has focused on both these mechanisms. The studies in this application are to further explore these two mechanisms. The specific aims are: (i) to investigate signaling, maturation and regulation of 5-4 receptors by morphine administration in vivo; (ii) to study the role of heterodimerization between opioid receptors and other heptahelical receptors, and (iii) to explore the physiological involvement of recently identified non-classical processing enzymes in the regulation of opioid and other neuropeptide levels. The studies described in this grant application will provide critical information on early events that regulate opioid receptor function. Elucidation of the cellular pathways involved in modulation of receptor function is a compelling strategy for identifying appropriate pharmacological interventions for drug addiction. This Award will allow the candidate to focus on research in the field of opioid peptides and their receptors. In addition, this Award will help mentor the next generation of researchers interested in exploring novel mechanisms and identifying novel targets for the treatment of drug abuse disorders.