CANNABIONOID RECEPTOR PHARMACOLOGY AND BIOCHEMISTRY

描述（由申请人提供）：这是一个研究科学家奖（RSA），授予Allyn C. Howlett博士，他的学术经历包括宾夕法尼亚州立大学生物化学学士学位，罗格斯大学药理学和毒理学博士学位，弗吉尼亚大学阿尔弗雷德G.吉尔曼博士后工作，并在圣路易斯大学医学院任教20年。他是北卡罗来纳中央大学朱利叶斯L.钱伯斯生物医学/生物技术研究所生物系终身教授和神经科学/药物滥用研究项目主任。豪利特博士的研究主要集中在CB1受体的药理学、生化和细胞调控方面。她的目的是维持一个活跃的研究实验室，让学生、研究员和访问科学家可以交流思想和分享专业知识。为了实现这一目标，豪利特博士正在寻求这个RSA，以便有足够的研究时间来进行她的研究，指导学生和研究员，并保持研究合作。RSA还将通过参与研究会议和短期课程，以及与其他研究科学家的交流，促进持续的专业发展。Howlett博士的研究项目已被nida资助的两个R01基金描述。“大麻素受体结构-活性关系”研究了受体与各种化学类配体（大麻素、氨基烷基醇、类二十烷和芳基吡唑）的相互作用，以努力定义高亲和力配体-受体结合和功效的要求。这个项目需要与合成化学家和计算化学家密切合作。“神经细胞和大脑中的大麻素受体”解决了CB1受体通过选定的G蛋白亚型及其随后的信号转导途径（腺苷酸环化酶、丝裂原活化蛋白激酶（MAPK）和其他激酶、Ca2+动员和一氧化氮合酶（NOS）激活）引起反应的信号机制。该项目还研究了细胞通过可逆的棕榈酰化和磷酸化的翻译后修饰调节信号转导的机制。

DESCRIPTION (provided by applicant): This is a Research Scientist Award (RSA) for Dr. Allyn C. Howlett, whose academic experience includes a B.S. cum laude in Biochemistry from Pennsylvania State University, a Ph.D. in Pharmacology and Toxicology from Rutgers University, post-doctoral work with Alfred G. Gilman at the University of Virginia, and 20 years on the faculty at Saint Louis University School of Medicine. Dr. Howlett is a tenured Professor in the Department of Biology and Director of the Neuroscience/Drug Abuse Research Program at the Julius L. Chambers Biomedical/Biotechnology Research Institute at North Carolina Central University. Dr. Howlett's research effort is concentrated on the pharmacological, biochemical and cellular regulation of the CB1 receptor. Her intention is to maintain an active research laboratory in which students, fellows, and visiting scientists can exchange ideas and share expertise. Toward this goal, Dr. Howlett is seeking this RSA in order to allow ample research time to conduct her research, mentor students and fellows, and to maintain research collaborations. The RSA will also foster continued professional development through participation in research meetings and short courses, and communication with other research scientists. Dr. Howlett's research projects have been described by two NIDA-funded R01 grants. "Cannabinoid Receptor Structure-Activity Relationships" examines the receptor interactions with ligands of various chemical classes (cannabinoid, amincialkylindole, eicosanoid and arylpyrazole) in an effort to define the requirements for high affinity ligand-receptor association and efficacy. This project involves close collaboration with synthetic chemists and computational chemists. "Cannabinoid Receptors in Neuronal Cells and Brain" addresses the signaling mechanisms by which the CB1 receptor evokes its response through selected G protein subtypes and their ensuing signal transduction pathways [adenylyl cyclase, mitogen-activated protein kinase (MAPK) and other kinases, Ca2+ mobilization and nitricoxide synthase (NOS) activation]. The project also examines the mechanisms by which the cell regulates signal transduction through the reversible post-translational modifications of palmitoylation and phosphorylation.