Molecular effects of mind-body intervention on GC sensitivity and immune function

描述（由申请人提供）：这是一份美国加州大学旧金山分校博士后Jeffrey Milush博士的K01奖申请。米鲁什博士正在成为一名年轻的研究者研究替代医学干预的能力以重置免疫系统的神经内分泌调节。K01奖将为Milush博士提供必要的支持，以实现以下目标：(1)成为免疫功能神经内分泌调节的分子和流式细胞分析专家；(2)研究身心干预对免疫细胞功能的影响；（三）在临床研究中运用生物统计学方法；(4)开发独立研究事业所需的资源。为了实现这些目标，Milush博士组建了一个指导团队，其中包括一位主要导师Douglas Nixon博士（实验医学部副主任，其实验室研究免疫细胞对压力和一系列病原体的反应）和三位共同导师：Frederick Hecht博士（医学教授，UCSF Osher综合医学中心研究主任，两项nccam资助的身心干预研究的联合首席研究员）；Margaret Kemeny博士，精神神经免疫学和实验室应激范式方面的专家，具有临床试验经验；以及Peter Bacchetti博士，他是目前最先进的临床研究生物统计分析专家。委员会成员将定期与Milush博士会面，讨论结果、进展、潜在问题和未来方向。此外，教学课程、讲座和研究会议都经过精心挑选，为Milush博士提供了额外的培训，这将有助于他过渡到一个完全独立的研究者。该项目的目标是通过改进和验证用于评估糖皮质激素受体表达和功能的新型流式细胞分析方法，对免疫反应的神经内分泌调节机制进行更详细的了解（目的1）。新的检测方法将用于确定体内皮质醇水平是否与免疫细胞中糖皮质激素受体表达相关（目的2）。最后，这些新颖的基于流式细胞术的分析将用于理解身心干预如何“重置”神经内分泌和免疫系统之间重要的双向通信（目的3）。这项研究将为更大、更全面的身心干预改变神经内分泌信号和免疫系统功能的机制研究奠定基础，该研究将在K奖期结束前的R01基金申请中进行。公共卫生相关性：更全面地了解神经内分泌对免疫细胞功能的控制，对于理解心身干预通过调节神经内分泌信号影响免疫功能的分子机制非常重要。

DESCRIPTION (provided by applicant): This is an application for a K01 award for Dr. Jeffrey Milush, a post-doctoral fellow at the University of California, San Francisco. Dr. Milush is establishing himself as a young investigator researching the ability of alternative medical interventions to reset neuroendocrine regulation of the immune system. This K01 award will provide Dr. Milush with the support necessary to accomplish the following goals: (1) to become an expert in molecular and flow cytometric analyses of neuroendocrine modulation of immune function; (2) to conduct investigations of the affects of mind-body interventions on immune cell function; (3) to implement biostatistical methods in clinical studies; and (4) to develop the resources necessary for an independent research career. To achieve these goals, Dr. Milush has assembled a mentoring team comprised of a primary mentor, Dr. Douglas Nixon, Associate Chief of the Division of Experimental Medicine, whose laboratory studies immune cell responses to stress and an array of pathogens, and three co-mentors: Dr. Frederick Hecht, Professor of Medicine, Research Director of the UCSF Osher Center for Integrative Medicine, and co-Principal Investigator on the two NCCAM-funded mind-body intervention studies; Dr. Margaret Kemeny, an expert in psychoneuroimmunology and laboratory stress paradigms with experience in clinical trials; and Dr. Peter Bacchetti, an expert in current state-of-the-art biostatistical analysis of clinical studies. Committee members will meet with Dr. Milush regularly to discuss results, progress, potential problems, and future directions. Furthermore, didactic courses, lectures, and research conferences have been carefully selected to provide Dr. Milush with additional training that will facilitate his transition to a completely independent investigator. The goal of this project is to develop a more detailed mechanistic understanding of neuroendocrine regulation of immune responses through the refinement and validation of novel flow cytometric assays for the assessment of glucocorticoid receptor expression and function (Aim 1). The novel assays will then be used to determine whether in vivo cortisol levels correlate with glucocorticoid receptor expression in immune cells (Aim 2). Lastly, these novel flow cytometry-based assays will be used to understand how mind-body interventions might 'reset' this important bi-directional communication between the neuroendocrine and immune system (Aim 3). This research will form the basis for a larger, more comprehensive investigation of the mechanisms by which mind-body intervention changes neuroendocrine signaling and immune system function in an R01 grant application before the end of the K award period. Public health relevance: A more complete understanding of neuroendocrine control of immune cell function is important for understanding the molecular mechanisms by which mind-body interventions affect immune function through modulation of neuroendocrine signaling. PUBLIC HEALTH RELEVANCE: Mind-body interventions, such as meditation and yoga, may have important effects on the immune system in part through the effects of these interventions on stress hormone signaling pathways. Our understanding of the potential effects of these interventions on the immune system is limited however, by gaps in our knowledge of how changes in stress hormone levels potentially achieved by these interventions actually affect the immune system. The long-term goal of this application is to develop new assays necessary to study the mechanisms by which stress hormones control immune cell function and how mind-body interventions 'reset' this communication pathway.