Palo Alto Veterans Institute For Research

Programs: Predicting resilience in the human microbiome - david relman, mddr. David relman is the project director of one of pavir's largest, multi-year research projects. It is on the cutting edge of examining the human microbiome, the collective genomes of the micro-organisms that reside in humans. Specifically, the project aims to answer questions relating to resilience in the human microbiome. Humans have co-evolved with complex, dynamic microbial communities that play essential roles in nutrition, metabolism, immunity, and numerous other aspects of human physiology. Hence, maintenance and recovery of key beneficial services by the microbiota in the face of disturbance is fundamental to health. The goal is to identify features of the human microbiome that predict microbial community stability and resilience following disturbance. The breadth and magnitude of this project's impact are significant: the study team tests to predict microbial community responses to disturbance, and works on procedures to stabilize or restore beneficial microbial interactions as needed. A predictive understanding of the stability and resilience of the gut microbiota will advance the rational practice of medicine. This project's participant recruitment is nearly complete, and data collection has been optimized resulting in a reduction of technical variance and reduced complexity of the overall protocol. An additional area of recent progress has been in developing standards to use a liquid handling robot to facilitate several steps of the overall work flow.

a prospective investigation of the risks of opioid misuse, abuse, and addiction among patients treated with extended-release/long acting (er/la) opioids for treatment of chronic pain - seshadri mudumbai, md, ms. This study examines the magnitude of misuse, abuse, and addiction among patients who are treated with opioids for chronic pain while having comorbidity of opioid use disorder with other substance use and psychiatric disorders and estimates how the risk of these outcomes varies by the presence of risk factors among patients treated with opioids long-term. The public health crisis of opioid misuse, addiction and overdose is one of the most challenging issues faced by american society. The issue cuts across every socioeconomic level and geographic boundary. Every community in america has been touched by friends, family members or colleagues suffering from opioid addiction, and far too often, losing their lives to it. Over the past few years, the fda has taken many actions to help reduce the number of people who become addicted, or ultimately overdose from prescription opioids. To combat this epidemic, the fda mandated that pharmaceutical companies holding new drug applications (nda) of extended-release/long lasting (er/la) opioids conduct one or more studies to provide quantitative estimates of serious risks of misuse, abuse, addiction, overdose, and death associated with long-term use of opioids for management of chronic pain, among patients prescribed er/la opioid products. Although abuse and misuse of prescription opioids have increased over the past decade, there is debate about the magnitude of misuse, abuse, and addiction among patients who are treated with opioids for chronic pain. Further, although there appears to be comorbidity of opioid use disorder with other substance use and psychiatric disorder, there is insufficient data to estimate how the risk of these outcomes varies by the presence of risk factors among patients treated with opioids long-term.

a bioorthogonal approach to study mammalian aging - tony wyss-coray, ph. D. Aging is the major risk factor for most of the leading causes of death in the u. S. , including heart disease, cancer, stroke and dementia. Dr. Wyss-coray's laboratory is working on a new technology which will identify factors that can rejuvenate the brain and other organs and accelerate our understanding of the basic biology of aging. The wyss-coray laboratory is poised to facilitate the identificaton, localization, and tracking of factors secreated from specific organelles, cell types, or organs in vivo. This is truly innovative and has not been done before. The potential applications of this technology for disease and biological research in general could be enormous, and will get us closer to answering fundamental questions on what controls organismal aging. These questions include whether aging starts in one tissue and spreads to another, or starts in one cell type and spreads to other cells and tissues, or starts simultaneously in all cells, or driven by other factors. This project follows a previous groundbreaking discovery in dr. Wyss-coray's laboratory that soluble, heat labile factors in blood plasma are sufficient to accelerate brain aging or regenerate and rejuvinate old brains.

pavir is privileged to work with a large community of uniquely talented medical researchers across a broad spectrum of research areas as we fulfill our mission of advancing veterans and public health through innovative research. The range of research activities is broad and includes special emphasis on major disease categories, all of which are prevalent in the va's patient population. These include cardiovascular medicine, mental health, chronic inflammatory disease, stem cell/regenerative medicine, pain, sleep disorders, and many others. In addition to disease specific research, pavir is engaged in supporting research aimed at enhancing health care. Pavir's research portfolio includes comparative studies in which research teams are learning which treatments are superior to others, how to augment or improve standard of care, as well as how to enhance the operation of health care. Furthermore, pavir is supporting educational activities, especially in areas of advancing clinical care for veterans and fostering the professional development of our expert staff.