We are requesting funds for a Ventana Medical Systems Discovery XT(R) automated staining platform. The system automates immunohistochemical and in situ hybridization slide-based assays for the analysis of DNA, RNA and proteins in intact cells and tissue. The advantage of this approach is that molecular markers can be examined in relation to the histopathologic architecture or morphology of the tissue or cells. Histopathological morphological examination is the gold standard of anatomic pathology and yields important information about the pathology and etiology of disease as well as forms the basis for translational diagnostic-prognostic correlations. The Discovery XT system is a multi-valent staining system that supports multiple slide based assays. These include: single and dual color immunohistochemistry (IHC), immunoflorescence (IF), chromogenic (CISH), fluorescent (FISH) and silver (SISH) in situ hybridization (ISH) as well as dual IHC/ISH and IHC/SISH applications. The instrument uses a "bake-to-stain" technology, allowing complete automation of all immunohistochemical and in situ steps to maximize reproducibility and consistency for paraffin, frozen and fresh samples. A wide variety of ancillary reagent and detection kits are available that further enhance the signal to noise for both human and animal studies. The system will be placed within the Experimental Pathology Shared Resource Laboratory at NYULMC, comprised of the Immunohistochemistry and Histopathology Core laboratories. The resource is administered by Office of Collaborative Science and operated by an experienced and trained staff. The instrument will be supported by the institution and instrument oversight will be administered by the instrument internal review board composed of 3 NIH funded major users and 2 NIH funded minor users, one of whom is external to the institution. The 8 NIH funded users combined will use 75% of the instrument time. The minor users group will occupy between 20-25% of instrument time. Any remaining time will be available to any of the over 100 users of the Experimental Pathology Shared Resource Core.