Lung disease originating in the period between the late canalicular stage to mature alveolarization and peak lung function, between limits of viability and early adulthood, remains a major cause of morbidity and mortality. Research to discover novel treatments for these disorders is limited by the rarity of access to normal and diseased human lung across this age span. Having, as the original Human Tissue Core (HTC) for the Molecular Atlas of Lung Development Program (LungMAP), created the BioRepository for INvestigation of Diseases of the Lung (BRINDL), the University of Rochester Medical Center (URMC) submits this application in response to RFA-HL-19-021 to continue to serve as the HTC for LungMAP Phase 2 (LungMAP II). BRINDL now contains over 200 human full lung sets, 50 normal by history and histopathology, spanning mid-late gestation to adult age, as well as an additional 70+ with specified disease. It will continue to be URMC-HTC responsibility to sufficiently identify and manage tissue sources to meet the overall Program goal to build an open-access, comprehensive, molecular atlas of the late- stage developing and maturing lung. As the HTC, URMC will collect, process, deposit, and distribute to the four LungMAP Research Centers (RCs), and ultimately the greater research community, human lung samples representing late gestation through early adulthood in forms that will support temporal and spatial characterization of molecular profiles of functionally or anatomically defined cell types in the developing lung. Per the RFA, the URMC-HTC will support the expansion of LungMAP to up to 25 years of age and to include neonatal and pediatric rare lung disease as well as normal lung development. Because of the concern and complexity in recovering high-quality pediatric lungs in a standardized manner and with as little ischemia-induced artifact as possible, and the need to meet all legal and ethical standards, we continue to choose to work primarily through elements of the United Network of Organ Sharing, the federally contracted Organ Procurement and Transplantation Network (OPTN), and two non-profit organizations to whom are referred non-transplantable donated organs suitable for research, The National Disease Research Interchange (NDRI) and the International Institute for the Advancement of Medicine (IIAM). NDRI and IIAM work well with the OPTN and with families who approach them directly during a pregnancy or illness expected to be lethal. In addition, we have contacts with Pediatric Pulmonary Centers around the country to identify potential sources for rare lung disease samples. Our goal is to provide an additional 250 lung set donations, or at minimum biopsies, for inclusion in the LungMAP BRINDL biorepository. Our URMC-HTC, in collaboration with Seattle Children?s Research Institute, will prepare the donated organs and tissues to meet the needs of the LungMAP Phase II RCs.
Respiratory disease accounts for 4 out of 10 global causes of mortality and for 10% of disability-adjusted life-years lost. In the US, chronic respiratory diseases are the fifth leading cause of death. The URMC- BRINDL(NL) Human Tissue Core is a cornerstone of the multi-center LungMAP effort to develop a 3-D molecular, cellular and structural atlas of normal human lung development from late gestation into early adulthood, that in entering Phase II will be expanded to allow comparison with neonatal and pediatric disease resulting from abnormalities in development and differentiation, in an ultimate effort to identify novel and more effective treatments and prevention of lung disease.
