Summary: In order to answer fundamental questions regarding the factors that govern ABO(H) immunity and incompatibility, new tools and approaches will need to be leveraged in a highly integrated manner. The need for a multidisciplinary approach is due to the intrinsic complexity of the questions this proposal seeks to address, including the complex structural features of ABO(H) post-translational antigens, the unique pathways responsible for anti-ABO(H) antibody formation that likely differ considerably from more well-studied pathways that dictate red blood cells (RBC)-induced alloimmunization and the role of innate immune factors and microbial glycans in shaping anti-ABO(H) antibody levels and specificity. Only through a program project grant (PPG) mechanism can the unique skills, Projects and Cores be established that are necessary to define fundamental features of ABO(H) immunity and incompatibility. To accomplish this, and therefore bring the broad range of investigators and overall expertise together that is necessary to address the key questions outlined in this proposal, an administrative core will be critical. This Core will not only oversee administrative aspects of the PPG but will also provide oversight of human subject biospecimen collection, provide a central node for data storage and sharing and directly coordinate with the existing biostatistical core at Brigham and Women’s Hospital/Harvard Medical School for data analysis. Given the distinct elements of each study, which range from defining key aspects of the microbiome, innate and adaptive immune interactions with blood group antigens and the actual ABO(H) blood group structure targets of incompatibility, coordinating these efforts across all Projects and Cores will be essential to successfully integrate, compare, and analyze all data. For data integration of human studies, it will be especially important that these studies use the same biospecimens. To this end, Core A will provide administrative oversight, oversee the biospecimen repository and facilitate data collection and storage of pre- clinical and human subject data so that data integration and comparison across all projects can be achieved. This will be done through the following specific aims: Aim 1: Provide administrative support for the PPG program. Aim 2: Oversee biospecimen collection and dissemination. Aim 3: Serve as a data repository for data integration, biostatistical analysis and data sharing with NIH data repositories. In summary, Core A will serve a critical role for the PPG by providing critical administrative oversight that is traditionally the role of an administrative core for a PPG program, while also serving as a biospecimen collection center and data coordinating center for the entire PPG.