Lung disease originating in the period of alveologenesis, between the limit of viability and early childhood, remains a major cause of illness and death. Research to discover novel treatments for these disorders is limited by the rarity of access to normal and diseased human lung in this age group. The University of Rochester Medical Center (URMC) submits this application in response to NHLBI RFA-HL-14-007 requesting proposals to enter into a cooperative agreement (U01) to serve as the Human Tissue Core (HTC) for the Molecular Atlas of Lung Development Program (LungMAP). It will be the responsibility of the HTC to identify and manage tissue source sites to collect the necessary tissues to meet the overall goal of this program which is, as stated in the RFA, to build an open-access reference resource by creating a comprehensive molecular atlas of the late-stage developing lung with data and reagents available to the research community. The atlas will integrate gene and protein expression profiles, transcriptome, epigenome, and other molecular characterizations with high-resolution anatomical information to provide molecular profiles of functionally or anatomically defined cell types in the developing lung. As the HTC, URMC will collect, process, deposit, and distribute normal late fetal and early childhood human lung samples to four LungMAP Research Centers (RCs). Because of the concern and complexity in recovering the 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 have chosen to work through elements of the United Network of Organ Sharing, the non-profit organization that manages the nation's federally contracted Organ Procurement and Transplantation Network (OPTN). Specifically, we have chosen to work with 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 are committed to working with the OPTN and with families who approach them because of a pregnancy that is expected to result in a perinatal death. We at URMC will prepare the donated organs to meet the needs of the RCs; at minimum we are prepared to obtain cone beam CT scans for evaluation of total volume, vascular and airway structure, prepare fixed, embedded and sectioned tissue and isolate specific cell populations by tissue dissociation and flow activated cell sorting. A working group of highly qualified Pathologists will consult for the HTC, to develop standard biorepository and assessment tools and to review specimens to assure quality and normality of the tissues chosen for study. We will work closely with the DCC to assure compatible data systems and ultimate open access to the collected data. We will also, from the inception, develop plans for the continued preservation and availability of these rare samples following the primary LungMAP funding.
Every year in the United States approximately 550,000 children are born prematurely. More than 50% of these preterm infants require multiple episodes of acute care for respiratory complications after leaving the hospital. The URMC-BRINDL(NL) human tissue core will be the cornerstone of the multi- center effort to develop the LungMAP, an atlas of normal human lung development at the structural, cellular, protein and gene level, to guide us toward novel and more effective treatment and prevention of lung disease in children. This opportunity to critically evaluate the complex processes of normal lung growth and development will serve as a reference for understanding the diseases that occur when the processes become abnormal.
