POST-TRANSLATIONAL REGULATION OF OPIOID RECEPTORS

描述（由申请人提供）： 候选人Lakshmi Devi博士拥有博士学位。他拥有加拿大温莎大学的学士学位，是西奈山医学院药理学和生物化学系的教授。她目前由两个独立的基金资助; DA 08863从NIDA/NIH-研究阿片受体的翻译后调节和NS 26880从NINDS/NIH-研究阿片肽生物合成的调节。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。高级科学家奖将通过减轻大量的教学和行政工作来促进这一点。该计划得到了药理学和生物化学系以及学校的全力支持。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。在这项资助申请中提出的研究的目标是研究新的机制，如受体二聚化，可以调节阿片受体的功能，并探讨参与神经肽水平的调节加工酶。 具体目标是：（i）研究阿片受体类型之间在调节受体功能中的异源二聚化，（ii）探索阿片受体和其他GPCR之间在调节受体功能中的异源二聚化的作用，（iii）描绘参与二聚化的阿片受体的结构域和残基，和（iv）探索神经肽生物合成中加工酶的生理参与。 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。

DESCRIPTION (provided by applicant): The candidate, Dr. Lakshmi Devi holds a Ph.D. degree from the University of Windsor, Canada and is a Professor in the Department of Pharmacology and Biological Chemistry, 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 opioid peptide 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 Award will facilitate this by relieving considerable amount of teaching and administrative duties. This plan has the full support of the Department of Pharmacology and Biological Chemistry and of the School. The focus of studies in Dr. Devi's laboratory has been to explore molecular mechanisms modulating opioid receptor function. The objectives of the studies proposed in this grant application are to examine novel mechanisms such as receptor dimerization that can modulate opioid receptor function and to explore the involvement of processing enzymes in the regulation of neuropeptide levels. The specific aims are: (i) to investigate heterodimerization between opioid receptor types in modulating receptor function, (ii) to explore the role of heterodimerization between opioid receptors and other GPCRsin modulating receptor function, (iii) to delineate the domains and residues of opioid receptors involved in dimerization and (iv) to explore the physiological involvement of processing enzymes in neuropeptide biosynthesis. The studies described in this grant application will provide critical information on early events that modulate 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.