Histopathology and Microscopy Core (V. Lindner, Core Director) The current Histopathology and Microscopy Core was established in 2004 within the COBRE in Stem and Progenitor Cell Biology (8P20GM103465), with Dr. Volkhard Lindner as the Core Director. Services included fixation, embedding, and processing of specimens for frozen and paraffin embedded sections and a spectrum of routine and specialty histological stains and basic immunohistochemistry. Our staff has expertise to develop and optimize immunohistochemistry procedures, including antigen retrieval, optimization in archival tissues, and various detection methods. The success of this Core attracted users from our sister COBRE in Vascular Biology, other investigators at Maine Medical Center, and regional clients, including from neighboring IDeA states. Our services were in high demand, and led in 2011 to our COBRE in Vascular Biology (P30GM103392) co-funding the Histopathology Core to increase research staff for expanded capacity, and add tissue microarray services. This co-funding mechanism has been extremely effective, allowing for efficient expansion of services. The Core with its current staff (Core Director and two full-time staff members) performs more than 30,000 procedures annually and in the past 14 years has directly supported close to 200 publications. During Phase I of this COBRE in Mesenchymal and Neural Regulation of Metabolic Networks, plastic embedding and sectioning as well as histomorphometry were established to meet demands by COBRE projects. To improve efficiency, mineralized tissue histology services have now been consolidated with services provided by the COBRE supported Histology and Imaging Core at the nearby University of New England. Efficiency and capacities were also increased during Phase I by acquisition of a larger tissue processor that uses solvents much more efficiently, thereby reducing costs and hazardous waste. As part of Phase II of this COBRE application, we propose to integrate microscopy and confocal microscopy services under the directorship of Dr. Prudovsky to meet the needs of Phase II supported projects and other federally funded research. Aim 1 of this core is to continue to provide outstanding services and training in a full suite of histopathology services. Aim 2 is to seamlessly integrate microscopy and confocal microscopy services and training into our workflow, to better serve the needs of our COBRE investigators and other users of this shared resource. COBRE investigators will receive these services at no charge, and other investigators enjoy highly competitive pricing. As in the past, the Core will also continue to offer its extensive and growing spectrum of services related to histology with full utilization of existing equipment and instrumentation garnered from previous COBRE support, as encouraged by NIGMS.