The overall goal of this PPG application is to develop a mechanistic understanding of the cellular and molecular basis for PD1 and LAG3 interaction that regulates T cell function in autoimmunity, cancer and chronic viral infections. Core D will provide sophisticated and relevant technologies and expertise to PPG investigators for understanding how the interplay between PD1 and LAG3 affects cellular interactions and relevant molecular pathways in intact experimental tissues from mice with autoimmune disease (Project 1), cancer (Project 2) and chronic viral infection (Project 3).
The Aims of this Core are:
AIM 1 : To perform in situ biomarker profiling of relevant cells and associated molecules. Core D will use several complementary approaches to analyze tissue immunopathology, including immunohistochemistry (IHC) and immunofluorescence microscopy. Core D also will develop protocols to visualize new molecules, based on results from PPG projects and Core C.
AIM 2 : To perform image quantification using computer-assisted morphometry to assess antigen density, distribution, architecture, and co-expresssion patterns. These data will interface with data generated by Core C and PPG projects, as well as metrics generated from conventional histology (e.g., qualitative assessment and grading of lesion severity) and clinical parameters (e.g. survival and weight loss) Core D will interact extensively with all three Projects, with Core A for statistical support for image quantification, and Core C by developing new staining protocols for cellular and histologic investigation of key genes that Core C determines are regulated by PD1 and LAG3.
PD1 and LAG3 are critical mediators of tolerance and prevent autoimmunity, but limit effective immunity to cancer and chronic infections. A mechanistic understanding of PD1/LAG3 synergy is needed to learn how to most effectively modulate these receptors to treat cancer, chronic infection and autoimmunity. Core D will help define these mechanisms by analyzing immunopathology in target tissues.
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