The instrument requested is a BD LSR-Fortessa, a high dimensional flow cytometer with 5 lasers, for the acquisition of 20 different parameters, and ability to perform detailed phenotypical and functional characterization of cellular populations and subsets. Given the myriad of cell types that have been identified in the peripheral blood and other tissue compartments, the ability of standard flow cytometers in characterizing these cells in a comprehensive manner would require a collection of large amount of blood or other biological specimens. Use of a high dimensional cytometer not only decreases dramatically this requirement, but also facilitates the discovery of new cellular populations, that otherwise would not be identified by low dimensional immunophenotyping. This is possible thanks to simultaneous assessment of cell surface proteins, intracellular phosphoproteins, cytokines, nuclear factors and other functional readouts. The ability of high dimensional cytometers to finely define cellular subsets (e.g. T cells, B cells) from complex mixtures such as blood and tissues, improves the likelihood of identifying cells relevant in disease pathogenesis, vaccination, and response to clinical treatment. This particular attribute is necessary to tackle and dissect complex conditions that arise during ageing (e.g. neurodegeneration) and diseases such HIV and cancer and that are currently investigated by VA researchers at the STVHCS. This instrument will be used to support the following research projects of the following VA researchers: (1) Sunil K. Ahuja M.D. - Host Genetic Determinants of HIV Pathogenesis (NIH/NIAID MERIT Award), Immune responses and host defenses in a large US HIV- population of military relevance [U.S. Air Force Medical Service Research Program (59th Medical Wing Intramural Award] and Center for Personalized Medicine: Systems of Biology of Inflammation and Immunity (VA ORD). (2) Robert Clark M.D. -Analysis of Olfactory Dysfunction for Early Diagnosis of Parkinson's Disease (VA Merit). (3) Senlin Li, M.D. - Macrophage-mediated gene delivery of neurotrophic factors for Parkinson's disease (VA Merit). (4) James Freeman, Ph.D. - Role of CD44 in adaptive plasticity of pancreatic cancer (VA Merit). (5) Ricardo Aguiar, M.D., Ph.D. - Non-coding RNAs at the interface of aberrant NF-kB signals and lymphomagenesis (VA Merit). This instrument will also be used as a focal point to form collaborations among and between these investigators, as well as recruitment of new investigators into the STVHCS.
Immune and inflammatory responses play a central role in multiple diseases that are prevalent in our veterans. We are requesting an instrument that will allow us determine with high precision and clarity this immune and inflammatory response. Thus, the acquisition of the requested instrument (flow cytometer) will have a sustained and long-term impact on our ability to identify cellular risks factors, mechanisms and pathways involved in diseases such as ageing-associated neurodegeneration (Alzheimer's, Parkinson's disease), HIV & cancer. The information generated will provide a blueprint to guide public health policy and treatment recommendations, direct new pathogenesis research and identify individuals who might be ideal candidates for novel immune-based and potentially curative strategies. The instrument requested has a long-standing track record in high-quality, high-impact research and it is anticipated that this level of productivity will be achieved via this instrument.
