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.
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.
|Gurfein, Blake T; Davidenko, Olga; Premenko-Lanier, Mary et al. (2014) Environmental enrichment alters splenic immune cell composition and enhances secondary influenza vaccine responses in mice. Mol Med 20:179-90|