Stress Reduction Studies in Mice and Humans

描述（由申请人提供）：本K 01指导研究科学家开发申请的目的是将候选人培养为翻译研究者，专注于基础科学和临床研究的桥接领域，以加速以补充和替代医学（CAM）为中心的机制研究。该K 01将为Gurfein博士提供必要的支持，以实现以下目标：（1）进一步开发和验证一种新型的减压动物模型，该模型可用于推进受CAM相关减压干预影响的生物学途径的测试;（2）获得临床研究，生物信息学和高级生物统计学方面的培训;（3）获得设计和实施临床研究的关键经验（4）获得尖端基础科学技术的专业知识，例如应用DNA微阵列研究CAM干预措施;以及（5）开发独立研究生涯所需的资源。为了实现这些目标，Gurfein博士组建了一个指导团队，由主要导师，医学教授Frederick Hecht博士，加州大学旧金山分校Osher中西医结合中心研究主任，NCCAM资助的P01赠款的主要研究员身心互动，以及两位共同导师组成：道格拉斯尼克松博士，医学教授，加州大学旧金山分校实验医学部副主任，他的实验室研究免疫细胞对压力和一系列病原体的反应;史蒂夫科尔博士，加州大学洛杉矶分校医学副教授和影响基因表达的社会环境因素的专家。除了广泛的指导，教学课程，讲座和研究的精心挑选的组合将提供博士Gurfein与培训和经验，他需要过渡到一个完全独立的调查员的角色。加州大学旧金山分校是一个理想的环境 因为它提供了先进的设施和设备，以及临床，基础科学和综合医学研究专家。将培训以文件形式进行 申请进行一项研究项目，旨在进一步开发一种减轻压力的动物模型，并将其用于识别和比较小鼠和人类因减轻压力而产生的免疫和基因表达变化。通过改变笼舍环境和通过包括旨在最小化小鼠应激水平的增强来实现小鼠的应激减轻。该研究的目的如下：验证并进一步开发一种小鼠模型，用于研究减压的效果和生物学机制（目的1）。将研究应激缓解动物的免疫细胞亚群的数量、比例和功能变化（目的2）。使用DNA微阵列，将评估来自减压小鼠和接受基于正念的减压训练的人类的分选淋巴细胞，以确定基因表达变化的相似性和差异（目标3）。这些目标建立在R 01中，其中小鼠减压模型将用于回答与公共卫生相关的问题，例如减压干预对流感疫苗接种和感染的影响。 公共卫生相关性：虽然人类研究表明，减压技术，如基于正念的减压，可以减少感知的压力，调节下丘脑-垂体-肾上腺轴活动，并可能影响免疫功能，但临床研究存在局限性，阻碍了对影响免疫系统，神经系统和其他生物系统的潜在途径的识别。这项工作代表了将身心相互作用和其他减压CAM实践的研究扎根于基础科学的重要一步，并将为研究减压对现有传染病，神经退行性疾病和其他慢性疾病模型的影响提供模块化工具。更全面地了解由减压调节的潜在分子途径对于确定减压CAM干预措施影响健康结果的方式非常重要。

DESCRIPTION (provided by applicant): The purpose of this K01 Mentored Research Scientist Development application is to develop the candidate as a translational investigator focused on bridging areas of basic science and clinical research to accelerate mechanism-focused investigations of complementary and alternative medicine (CAM). This K01 will provide Dr. Gurfein with the support necessary to accomplish the following goals: (1) to further develop and validate a novel animal model of stress reduction that can be used to advance testing of biological pathways influenced by CAM-related stress reduction interventions; (2) to acquire training in clinical research, bioinformatics, and advanced biostatistics; (3) to gain pivotal experience designing and implementing clinical research (4) to gain expertise in cutting edge basic science techniques such as the application of DNA microarrays to study CAM interventions; and (5) to develop the resources necessary for an independent research career. To achieve these goals, Dr. Gurfein has assembled a mentoring team comprised of a primary mentor, Dr. Frederick Hecht, Professor of Medicine, Director of Research at the Osher Center for Integrative Medicine at UCSF, and principal investigator of a NCCAM funded P01 grant on mind-body interactions, and two co-mentors: Dr. Douglas Nixon, Professor of Medicine and Associate Chief of the Division of Experimental Medicine at UCSF, whose laboratory studies immune cell responses to stress and an array of pathogens; and Dr. Steve Cole, Associate Professor of Medicine at UCLA and an expert on socioenvironmental factors that affect gene expression. In addition to extensive mentoring, a carefully selected combination of didactic coursework, lectures, and research will provide Dr. Gurfein with the training and experience that he requires to transition to a role of fully independent investigator. UCSF is an ideal environment for the proposed training because it provides access to cutting edge facilities and equipment and to experts in clinical, basic science, and integrative medicine research. This training will be applied to conduct a research project that aims to further develop an animal model of stress reduction and apply it to identify and compare the immunologic and gene expression changes that result from stress reduction in mice and humans. Stress reduction in mice is achieved through altering the caging environment and by including enhancements that are designed to minimize mouse stress levels. The research addresses the following aims: To validate and further develop a mouse model that will be used to study the effects and biological mechanisms of stress reduction (Aim 1). Immune cell subsets from reduced-stress animals will be studied for changes in number, proportion, and function (Aim 2). Using DNA microarrays, sorted lymphocytes from reduced-stress mice and humans trained in mindfulness-based stress reduction will be assessed to identify similarities and differences in gene expression change (Aim 3). These aims build toward an R01 in which the mouse stress reduction model would be used to answer questions relevant to public health such as the effects of stress reduction interventions on influenza vaccination and infection. PUBLIC HEALTH RELEVANCE: Though human studies have shown that stress reduction techniques, such as mindfulness based stress reduction, can reduce perceived stress, modulate hypothalamic-pituitary-adrenal axis activity, and may affect immune function, clinical studies have limitations that hinder the identification of underlying pathways that influence the immune system, nervous system, and other biological systems. This work represents a significant step toward rooting the study of mind-body interactions and other stress-reducing CAM practices in basic science and will provide a modular tool for studying the effects of stress reduction on existing models of infectious disease, neurodegeneration, and other chronic illnesses. A more complete understanding of the underlying molecular pathways that are modulated by stress reduction is important for determining the ways in which stress reducing CAM interventions can influence health outcomes.