Research Pathology Shared Resource

PROJECT SUMMARY: RESEARCH PATHOLOGY SHARED RESOURCE The Research Pathology Shared Resource (RPSR) of the Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium provides a suite of cutting-edge tools to enable the analysis of complex cancer phenotypes in a spatially resolved manner. Understanding the intricate pathologic “social network” within tumors is essential to further develop our mechanistic understanding of cancer and translate those insights into effective cancer treatments. The RPSR offers a range of services including routine histopathology, custom immunohistochemical assay development, multiplex immunohistochemistry, novel antibody discovery and production, and spatial transcriptomics/proteomics. RPSR is led by two directors, each with unique but complementary areas of expertise. Amanda Koehne, DVM, PhD, is a comparative pathologist and cancer biologist with background in cancer models, tissue architecture, and histopathology methodologies. David Jellyman, MS, is a biologist with mastery in antibody discovery platforms. Together, the directors provide customized pathology research solutions, even when commercial antibody reagents are unavailable. RPSR directors aid researchers with experimental design, study interpretation, and training/deployment of software- based quantitative image analysis. RPSR is committed to outreach and training the next generation of cancer researchers through participation in three college and post baccalaureate internship programs and hosting high school students for lab tours and case-based learning exercises. RPSR works with investigators to generate novel, customized assays to address specific scientific questions. One such assay combining in situ hybridization with multiplex immunohistochemistry without sacrificing tissue morphological integrity allowed for visualization of CAR T cells in the tumor immune microenvironment (Wright et al. Immunol Methods 2021). This technique has been used for in vivo studies as well as clinical patient specimens to interrogate mechanisms of therapeutic success or failure. In the past five years, collaborations with investigators have resulted in over 122 peer-reviewed publications, support on 60 grants, and over 1500 individual requests for core services annually. Future plans for RPSR include expanding spatial transcriptomics offerings, incorporating artificial intelligence into the current digital image analysis platforms, and developing B cell culture-based antibody discovery workflows. As the Resource develops assays for in vivo and clinical research specimens, RPSR is poised to serve the expanding translational medicine and precision oncology programs across the Consortium. RPSR is committed to fostering a culture of continuous improvement and providing innovative, high-quality, cost-effective, and expeditious services to the Consortium and to broadly contribute to the basic and translational mission of the Consortium.