Mentorship in the Endocrinology of Sleep

本申请的总体目标是获得K24职业中期研究者奖，以患者为导向的研究 是促进培训有前途的初级研究人员在尖端的面向患者的研究有关如何 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， 最近更新了加州大学洛杉矶分校的CTSI，其中包括一个非常成功的KL 2计划。刘博士领导了一个竞争性的- 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，该项目得到了为期5年的NHLBI R 01的支持 “睡眠限制的激素机制”，目前是在其第三年。在他10年的指导生涯中， 他已培训了16人：10人留在学术医学领域，另外2人在行业相关患者领域 导向研究。在他的指导下，他的三名学员获得了美国主要的青年调查员奖。他 继续支持，指导，并与以前的学员一起发表，通常在他们离开实验室很久之后。 睡眠紊乱会导致胰岛素抵抗，促进不良的食物选择，并在节食时减少脂肪损失， 从而降低标准减肥计划的有效性。然而，心脏代谢 睡眠障碍的后果并没有得到社会的充分认识，证明其合理性的证据基础 由于心脏代谢健康的原因，社区睡眠模式正在发生广泛的变化。示出 睡眠限制导致心脏代谢不良的机制，特别是老年人 是提供这些数据的关键步骤。刘博士的目标是指导下一批 独立的临床科学家专注于将睡眠与饮食和锻炼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。目标1将显示下丘脑-垂体-肾上腺 和下丘脑-垂体-性腺机制，导致睾酮-皮质醇失衡时，睡眠是 仅限于老年男性和女性（每组20例）。在此过程中，学员将学习内分泌生理学， 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将 确定这些机制中的性别差异，学员将学习统计方法和摘要/演示/ 手稿准备。目标3要求受训者发现睡眠限制导致 胰岛素抵抗和改变食欲或食物摄入。某些炎症介质、激素或因子 与种族或年龄有关的问题。目标3满足了学员对拥有第二个 更快完成的项目，更具探索性，并由他们的兴趣和可用资源驱动， 发展一条与导师的研究相辅相成、相互独立的研究路线。综上所述各项 实验将产生新的知识之间的关系，睡眠和荷尔蒙心脏代谢， 生殖健康，提供广泛的培训机会，并产生未来的R和K提案。

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.