We have entered the post-genomic era. It is now more important than ever to understand the final output of genomic changes. In addition, there are many alterations that take place at the metabolic level than drive pathological conditions independent of genomic events. Therefore the key to understanding how cells and organs function under physiological and pathophysiological conditions necessitates deciphering the myriad of metabolic and regulatory pathways that govern how cellular and organism respond to various conditions and how it integrates multitudes of inputs and across vast dimensions (from subcellular to the individual to groups of individuals). This has been loosely defined as the field of Metabolomics. However, the study of metabolomics, which include thousands of lipids and small molecules, is difficult because of the chemical nature of many of these metabolites and because of the intricacies of metabolic interconnections and networking. Therefore, this field of study requires unique expertise such as advanced analytical and synthetic chemistry as well as bioinformatics and modeling. Nonetheless, the field has become fundamental to a modern understanding of human health and disease, whether it is how nutrients work, how exposure to foods interacts with the body and with diseases, or how metabolites can serve as key regulatory molecules and mediators of pathobiology. VA investigators need to be able to carry out hypothesis driven targeted metabolomic analysis based on the pathways they study. To this end, an Agilent 6495 triple quadruple mass spectrometer is required. In addition, due to the need of investigators to study lipophilic, non-polar and polar metabolites, dedicated HPLC equipment is required for analyte separation. Many projects have generated pilot data on the Agilent 6495 triple quadrupole instrument. For example, investigators studying cancer are interested in metabolic pathways related to glucose metabolism, glycolytic, pentose phosphate pathway, TCA cycle intermediates. Non-polar lipid derived metabolites including phosphatidylinositol, ceramide and diacylglycerol in cancer, insulin resistance, metabolic syndrome, cardiovascular diseases and neuropathology.
This is a new application requesting funds to support the acquisition of an Agilent 6495 triple quadruple mass spectrometer and associated HPLC equipment to enhance, support and promote the function of the Metabolomics and Lipodomics capabilities at the Northport VA facility. The requested instrument will be located in the existing metabolism laboratory at the Northport VA where it will support critical functions and capabilities for the analysis of metabolites and bioactive lipids in disease-oriented research and further the capabilities to create a hub of metabolomics excellence that will serve not only key investigators at the Northport VA but also the greater VA system as a whole. In addition, this will serve to engage outside investigators into collaborations with VA researchers to further the medical research goals of the VA.
