The responsibility of the Department of Veteran Affairs is to provide excellent medical care to those who have served their country in the Armed Services. The Office of Research and Development within the Department of Veteran Affairs is concerned with improving medical care of Veterans through better understanding of the basic components of disease, the clinical manifestations of conditions requiring medical treatment, the understanding and improvement of health service delivery, and the science of rehabilitation. This application requests support for shared instrumentation that provides critical infrastructure to researchers seeking to improve Veteran health through each of those mechanisms. The research community at the Providence VA Medical Center has a long history of excellence in each of these domains. From the biological bases of cardiovascular disease, to the careful characterization of psychopathology, to the Center of Innovation for Long Term Services, to the outstanding Rehabilitation work for mental and physical disorders the Providence VAMC has been enormously productive in the area of Veteran-centric medical research. Consistent with this history of excellence is the requirement for cutting edge research infrastructure to serve this productive research community. Accordingly, this application requests support for two pieces of scientific instrumentation that may further extend the impact and innovation of numerous VA researchers. The first instrument that we are seeking support for is a real-time PCR machine to replace aging, outdated technology currently in use. This equipment allows for the assessment of specific genetic variation in a cost- effective manner. In addition to the ability to assay genetic information, increasingly we are also using this machine to determine levels of gene expression. As this machine will replace obsolete equipment (no longer supported by the manufacturer), it will fit seamlessly into our existing workflows. The second instrument that we are seeking support for is an automated liquid handling system to integrate into our existing Illumina array reader system. This technology allows the economical examination of genetic, epigenetic and gene expression differences across the entire genome. This ?omic? level of analysis is complimentary to the individualized approach described above. As our work using the Illumina micorarrays has increased over the years we have identified the liquid handling steps as the limiting factor in our throughput. Obtaining this Tecan system will remove a critical bottleneck in our ability to keep this workflow moving efficiently. As this liquid handling system will be integrated into an existing workflow, we have the expertise and need to utilize this equipment. Obtaining this new equipment would position us to complement efforts of the VA-wide Million Veteran Project (MVP). That is, the MVP relies on the clinical data in CPRS, whereas the PVAMC genomics lab allows examination of the same kind of genetic variation in samples from those who have participated in controlled trials. By leveraging the massive MVP observational data with local controlled studies we increase our chances of successfully identifying genetic targets that will eventually point to improved therapeutics for our Veterans. Examples of studies that will benefit from the proposed equipment include Dr. Tracie Shea's studies of PTSD, Dr. Primack's studies of suicidality, Dr. Phillip's study of the neural bases of psychopathology, Dr. Wu's study of health service utilization, and numerous other minor users investigating conditions critical for Veteran health.
This Shared Equipment Evaluation Program application seeks to obtain two pieces of equipment that will benefit numerous researchers at the Providence VAMC to improve Veteran care. The first piece of equipment is used to assay individual genetic variation in samples from Veterans and others with Veteran-relevant medical conditions (e.g., addiction, diabetes, heart disease, depression, PTSD, etc.). The second piece of equipment is used to assay samples on a comprehensive scale (e.g., genomic scans). By examining individual differences at the targeted (first machine) and 'omic levels (second machine), the hope is to identify unique targets for intervention using a precision medicine approach. Inherent to this line of research is the consideration of the possibility that not all treatments work equally well in all individuals. By studying these individual differences at the molecular level, we hope to tailor treatments to Veterans based upon their unique genetic and epigenetic background.
