The purpose of this proposal is to seek funds for the purchase of an LTQ OrbiTrap XL Mass Spectrometer. This instrument will expand and upgrade mass spectrometry capabilities within the Northeastern Ohio region, advancing research programs within the Cleveland Clinic (CC) and its partner institution, Case Western Reserve University (CWRU) other Cleveland CTSA member institutions and Cleveland State University (CSU). Major Users all have NIH-funded research grants, including recent multiple Program Project Grants and SCCOR programs, all which have Projects that rely heavily on using mass spectrometry to ask, investigate and answer key questions concerning major diseases that affect human health. Due to the absence of available high resolution instrumentation in the region for metabolomics-based studies the Major Users in this proposal now have to schedule time many months in advance to obtain access to this technology and/or travel to distant (>550 miles) institutions. As detailed in the application, supported projects primarily include biomarker discovery and clinical/translational studies nearly all of which also utilize the NCRR-funded Cleveland CTSA. The requested mass spectrometer provides the high resolution capabilities that allow unbiased metabolomics studies to be performed. Availability of this instrument will assure area investigators access high resolution mass spectrometry, while enhancing the versatility, sensitivity and specificity required for their projects. This analytical activity will be conducted within our existing Mass Spectrometry Core II, which provides support to investigators at CC, CWRU, CSU and neighboring institutions by performing structural elucidation studies, biomarker quantification, protein sequencing/identification, and related services. Mass spectrometry is increasingly being used as an analytical tool by CC and partner institution investigators, with demand greatly outpacing availability, resulting in significant delays in access, and hampered productivity. The acquisition of the requested mass spectrometer is essential to provide an unmet need for instrumentation to perform metabolomics-based investigations. Cleveland Clinic has committed substantial resources to the development of mass spectrometry in the region, including custom renovation of laboratory space for Mass Spectrometry Core II, personnel to oversee its operation, and a fiscal plan to insure its operation and maintenance for the long-term. PUBLIC HEALTH RELEVANCE: The major users group, of this shared mass spectrometry instrumentation grant, direct multiple very large clinical sample-based NIH-funded grants. The Major Users have projects that require the use of the requested instrumentation to ask, investigate and answer key questions concerning major diseases that affect human health. These projects primarily include disease biomarker discovery and clinical/translational studies that will allow and facilitate discovery of novel disease pathways and metabolites, early detection of disease states and/or provide prognostic evaluation of the disease state based upon clinical sample outcomes.