The main goal of this research program is to obtain in-depth profiles of how human innate and adaptive immune cells function in response to viral pathogens in tissues and understand how the circulating responses relate to those in tissues. We will specifically investigate the innate and adaptive immune response to cytomegalovirus (CMV), as a ubiquitous persistent virus of great clinical importance in immunocompromised individuals, particularly recipients of sold organ and hematopoietic transplants, infants and the elderly. We will use two sources of human samples for the proposed studies in all projects (Projects 1, 2, 3): deceased organ donors and peripheral blood from transplant patients from the Columbia Center for Translational Immunology (CCTI) Biobank. For Service aim 1, we will obtain and process multiple lymphoid and mucosal tissues from human organ donors. We have established the necessary protocols and collaborations with Columbia University Medical Center (CUMC) surgeons and LiveOnNY to obtain from research-consented organ donors, tissues that are not used for life-saving transplantation. We already have the infrastructure set up to obtain multiple lymphoid tissues (including spleen, peripheral, lung- and intestinal draining lymph nodes, tonsils and bone marrow), mucosal tissues (lungs, small and large intestinal sections) and other peripheral sites such as salivary glands from organ donors whose next-of-kin have consented for the use of tissues for research. The tissues will be processed in the laboratory and cell suspensions, and/or whole tissues will be distributed to all projects and to Core B for analysis. For service aim 2, we will obtain samples from transplant patients who develop CMV viremia through the CCTI Biobank which has a large repository of samples from 1000 recipients of solid organ (heart, kidney, liver) or hematopoietic cell transplants. There is an existing cohort of samples from 70 donors who developed CMV viremia and hundreds who did not for use as controls, with multiple timepoints and samples obtained for each donor. The CCTI biobank will provide blood samples form the existing repository and monitor all enrolled patients for the development of CMV viremia, maintain IRB protocols for obtaining samples, and will work with the clinicians to identify additional patients who develop CMV viremia and disease. This Clinical core will be responsible for coordinating all of the personnel, institutional assurance, protocols and MTAs necessary to acquire and process human tissues, and distribute samples to these projects, and will play a key role in the proposed HIPC program by providing novel samples from the diverse populations that are in New York City.
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