Mentorship in the Endocrinology of Sleep

睡眠内分泌学指导

基本信息

批准号：
10162642
负责人：
Peter Yiwen Liu
金额：
$ 11.96万
依托单位：
LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-05-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10162642
关键词：
Adrenal Glands Adult Age Amino Acids Anabolism Analysis of Variance Award Biology Carbohydrates Catabolism Chronic Disease Clinical Communities Complement Corticotropin Corticotropin-Releasing Hormone Cosyntropin Couples Data Desire for food Development Dexamethasone Diabetes Mellitus Diet Dose Eating Effectiveness Elderly Endocrine Endocrine Physiology Endocrinology Environment Equilibrium Ethnic Origin Fatty Acids Fatty acid glycerol esters Feedback Female Food Fostering Freezing Funding Future Goals Gonadal structure Gonadotropin Hormone Releasing Hormone Grant Health Hormonal Hormone imbalance Hormone secretion Hormones Hunger Hydrocortisone Hypothalamic structure Impaired cognition Individual Industry Inflammation Mediators Infusion procedures Institutional Review Boards Insulin Resistance Interdisciplinary Study Ketoconazole Knowledge Laboratories Learning Left Link Los Angeles Luteinizing Hormone Manuscripts Measures Mediator of activation protein Medicine Menopause Mentors Mentorship Metabolic Metabolic Diseases Metabolic syndrome Metabolism Midcareer Investigator Award in Patient-Oriented Research Modeling Moods Muscle Muscular Atrophy National Heart, Lung, and Blood Institute Non-Insulin-Dependent Diabetes Mellitus Osteoporosis Ovary Patients Physiological Pituitary Gland Pituitary-Adrenal System Population Postmenopause Prediabetes syndrome Predisposition Preparation Process Production Publications Publishing Reproductive Health Research Research Design Research Personnel Research Training Resources Risk Scientist Serum Sex Differences Sleep Sleep Deprivation Sleep Disorders Sleep disturbances Statistical Methods Steroid biosynthesis Stress Supervision Testing Testosterone Training Universities Virulence Factors Weight Gain Woman Work age related aged base biological adaptation to stress bone age cardiometabolism data cleaning diabetes risk diet and exercise dieting disorder risk expectation experimental study ganirelix healthy lifestyle hormonal signals insulin sensitivity interest male men metabolic abnormality assessment older men older women patient oriented research pituitary gonadal axis prevent programs recruit response sarcopenia sex skills sleep pattern statistical learning targeted treatment training opportunity weight loss program young adult

项目摘要

The overarching goal of this application for a K24 Midcareer Investigator Award in Patient-Oriented Research is to foster training of promising junior investigators in cutting edge patient-oriented research related to how sleep biology influences cardiometabolic health. It capitalizes on the established network and resources of the recently renewed UCLA CTSI that includes a highly successful KL2 program. Dr. Liu led a competitively- funded Endocrine and Cardiometabolic Program in Sleep Biology at the University of Sydney, and since 2012, he has led a similar interdisciplinary research program in Los Angeles supported by a 5 year NHLBI R01 “Hormonal mechanisms of sleep restriction” that is currently in its 3rd year. During his 10 years of mentoring, he has trained 16 individuals: 10 remaining in academic medicine and 2 others in industry-related patient orientated research. Three of his trainees won major US young investigator awards under his supervision. He continues to support, mentor, and publish with former trainees, often long after they left his laboratory. Disturbed sleep causes insulin resistance, promotes poor food choices, and curtails fat loss while dieting, thereby reducing the effectiveness of standard weight loss programs. However, the cardiometabolic consequences of disturbed sleep are not well recognized by the community, and the evidential bases to justify widespread changes to community sleeping patterns for cardiometabolic health reasons are evolving. Showing the mechanisms by which sleep restriction leads to cardiometabolic ill-health, particularly in older adults according to sex, are critical steps in providing these data. Dr. Liu's goal is to mentor the next cadre of independent clinical scientists focused on placing sleep alongside diet and exercise as part of healthy lifestyle, by understanding hormonal mechanisms and consequences of disrupted, inadequate or misaligned sleep. The work proposed in this application fulfill these goals. Aim 1 will reveal the hypothalmo-pituitary-adrenal and hypothalamo-pituitary-gonadal mechanisms that cause testosterone-cortisol imbalance when sleep is restricted in older men and women (20 in each group). In doing so, trainees will learn endocrine physiology and chronobiological study design, IRB processes, recruitment skills, and hands-on study management. Aim 2 will identify sex differences in these mechanisms, trainees will learn statistical methods and abstract/presentation/ manuscript preparation. Aim 3 requires trainees to discover new mechanisms by which sleep restriction causes insulin resistance and alters appetite or food intake. Certain inflammatory mediators, hormones, or factors related to ethnicity or age could be studied. Aim 3 fulfils broader expectations for trainees to have a second project that is faster to accomplish, more exploratory, and driven by their interests and available resources, to develop a line of research that complements and is separate from that of the mentors. Taken together, these experiments will generate new knowledge of the relationship between sleep and hormonal cardiometabolic and reproductive health, provide wide-ranging training opportunities, and generate future R and K proposals.

本申请的总体目标是获得 K24 职业生涯中期研究者奖（面向患者的研究）是为了促进对有前途的初级研究人员进行前沿的以患者为导向的研究的培训，这些研究涉及如何睡眠生物学影响心脏代谢健康。它利用了现有的网络和资源。最近，加州大学洛杉矶分校 CTSI 包括一个非常成功的 KL2 项目，刘博士领导了一个具有竞争力的项目。资助悉尼大学睡眠生物学内分泌和心脏代谢项目，自 2012 年以来，他在洛杉矶领导了一个类似的跨学科研究项目，并得到了 5 年 NHLBI R01 的支持 “睡眠限制的荷尔蒙机制”目前已进入第三个年头，在他的 10 年指导中，他培训了 16 人：其中 10 人从事学术医学，另外 2 人从事与行业相关的患者他的三名学员在他的指导下获得了美国主要的青年研究者奖。通常在前学员离开实验室很久之后，他仍然继续为他们提供支持、指导和出版。睡眠障碍会导致胰岛素抵抗，导致食物选择不当，并在节食时减少脂肪流失，从而降低了标准减肥计划的有效性。睡眠障碍的后果尚未得到社会的充分认识，并且缺乏证明其合理性的证据基础由于心脏代谢健康原因，社区睡眠模式正在发生广泛的变化。睡眠限制导致心脏代谢疾病的机制，尤其是老年人性，是提供这些数据的关键步骤。刘博士的目标是指导下一代骨干。独立临床科学家专注于将睡眠与饮食和锻炼一起作为健康生活方式的一部分，通过了解荷尔蒙机制以及睡眠中断、不足或失调的后果。本申请中提出的工作实现了这些目标 1 将揭示下丘脑-垂体-肾上腺。以及下丘脑-垂体-性腺机制，在睡眠时导致睾酮-皮质醇失衡仅限老年男性和女性（每组 20 人）。在此过程中，学员将学习内分泌生理学和时间生物学研究设计、IRB 流程、招募技能和实践研究管理目标 2。识别这些机制中的性别差异，学员将学习统计方法和摘要/演示/ 目标 3 要求学员发现睡眠限制导致的新机制。胰岛素抵抗并改变食欲或食物摄入量。可以研究与种族或年龄相关的目标 3 满足受训者拥有第二个目标的更广泛期望。完成速度更快、更具探索性、并由他们的兴趣和可用资源驱动的项目开发一系列与导师的研究相补充且独立的研究。实验将产生关于睡眠与激素心脏代谢之间关系的新知识生殖健康，提供广泛的培训机会，并提出未来的 R 和 K 建议。