Pathology

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Project Summary This Pathology Core (2) will provide a seamless translational infrastructure to support the research on RS tissues planned in this application. This will include the ex vivo expansion of primary RS samples in immunocompromised mice in an effort to generate in vivo RS primagraft models for provision of fresh or frozen RS cells for in vitro molecular and in vivo functional experiments. The RS samples will have full clinical annotation as well as molecular characterization (from Project 1/Core 3), and will be derived from patient samples already stored through the DFCI RS Biospecimen Core (1) as well as newly enrolled patients from DFCI and collaborating institutions. These models are a significant and increasingly appreciated tool for the analysis of newly identified genetic lesions, associated signaling and survival pathways, rational therapeutic targets and mechanisms of drug resistance. RS cells will be delivered by tail vein injection or directly implanted subcutaneously or beneath the renal capsule. These primagraft models could then be used to characterize biology and assess response to therapy of the RS cells. This Pathology Core will also: (i) provide FFPE archived samples from RS patients, (ii) provide histo-pathological analysis of human RS samples to be used in subsequent studies, (iii) generate tissue microarrays (and slides of CLL/RS pairs for functional validation, (iv) provide morphologic and histopathologic analysis of mouse RS samples in engineered mice, and (v) generate tissue arrays and slides to study histopathology and perform immunohistochemical characterization of mouse RS engineered mice.