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

身心干预对GC敏感性和免疫功能的分子影响

• 批准号: 8628635
• 负责人: JEFFREY MILUSH
• 金额: $ 13.15万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8628635
• 关键词: Address; Affect; Applications Grants; Binding; Biological Assay; Biostatistical Methods; Blood specimen; California; Cell Communication; Cell physiology; Cells; Chronic; Chronic stress; Clinical Research; Clinical Trials; Committee Members; Communication; Complementary and alternative medicine; Cytokine Suppression; Equilibrium; Flow Cytometry; Funding; Future; Glucocorticoid Receptor; Glucocorticoids; Goals; HIV-1; Health; Hormones; Hydrocortisone; Hypothalamic structure; Immune; Immune Cell Suppression; Immune response; Immune system; In Vitro; Individual; Integrative Medicine; Intervention; Intervention Studies; Investigation; K-Series Research Career Programs; Knowledge; Laboratories; Laboratory Study; Ligand Binding; Lipopolysaccharides; Measures; Medical; Medicine; Meditation; Mentored Research Scientist Development Award; Mentors; Mind-Body Intervention; Molecular; National Center for Complementary and Alternative Medicine; Neurosecretory Systems; Obesity; Pathway interactions; Patients; Pattern; Peripheral Blood Mononuclear Cell; Persons; Phosphorylation; Physiological; Postdoctoral Fellow; Principal Investigator; Production; Psychoneuroimmunology; Randomized; Regulation; Research; Research Personnel; Resistance; Resources; Sampling; San Francisco; Signal Pathway; Signal Transduction; Stress; T-Lymphocyte; Techniques; Technology; Testing; Training; Universities; Validation; Yoga; base; body-mind; career; cytokine; design; experience; hormone regulation; immune activation; immune function; in vivo; insight; intervention effect; lectures; meetings; monocyte; novel; pathogen; patient population; peripheral blood; professor; public health relevance; receptor expression; receptor function; response; symposium

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.

描述（由申请人提供）：这是一个K 01奖博士杰弗里米卢什，在加州大学，旧金山弗朗西斯科博士后研究员申请。Milush博士正在确立自己作为一名年轻研究人员的地位，研究替代医学干预措施重置免疫系统神经内分泌调节的能力。该K 01奖项将为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术分析专家;（2）调查身心干预对免疫细胞功能的影响;（3）在临床研究中实施生物统计学方法;（4）在临床研究中实施生物统计学方法。（4）开发独立研究生涯所需的资源。为了实现这些目标，Milush博士组建了一个指导团队，由主要导师道格拉斯尼克松博士和三位共同导师组成，他是实验医学部的副主任，他的实验室研究免疫细胞对压力和一系列病原体的反应：Frederick Hecht博士，医学教授，UCSF Osher中西医结合中心研究主任，她是NCCAM资助的两项身心干预研究的共同首席研究员; Margaret Kemeny博士，心理神经免疫学和实验室应激范式专家，具有临床试验经验; Peter Bacchetti博士，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博士提供额外的培训，这将有助于他过渡到一个完全独立的研究者。 本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术测定法，对免疫反应的神经内分泌调节进行更详细的机制理解（目的1）。然后，新的测定将用于确定体内皮质醇水平是否与免疫细胞中的糖皮质激素受体表达相关（目的2）。最后，这些新的基于流式细胞术的检测将用于了解身心干预如何“重置”神经内分泌和免疫系统之间的这种重要的双向通信（目标3）。这项研究将形成一个更大，更全面的调查机制的基础，通过该机制，身心干预改变神经内分泌信号和免疫系统功能在R 01赠款申请K奖结束前。公共卫生相关性：更全面地了解免疫细胞功能的神经内分泌控制对于理解身心干预通过调节神经内分泌信号影响免疫功能的分子机制是重要的。 公共卫生相关性：身心干预，如冥想和瑜伽，可能会对免疫系统产生重要影响，部分原因是这些干预措施对应激激素信号通路的影响。然而，我们对这些干预措施对免疫系统的潜在影响的理解是有限的，因为我们对这些干预措施可能实现的应激激素水平变化如何影响免疫系统的知识存在差距。这项应用的长期目标是开发必要的新检测方法，以研究应激激素控制免疫细胞功能的机制，以及身心干预如何“重置”这种沟通途径。