OVERALL ABSTRACT Child health is determined by multiple environmental forces; however, surprisingly little is known about the interactions of these forces. In addition, despite an emerging consensus that numerous gene-environment interactions determine child health, much remains unknown about how genetic and environmental factors combine to promote or prevent adverse outcomes. This Environmental influences on Child Health Outcomes (ECHO) Coordinating Center (CC) proposal seeks to further strengthen the broad children's health research community to increase the body of knowledge about these complicated effects by fostering collaboration among internal and external stakeholders and supporting the research of the ECHO Program to enhance the health of children for generations to come. The Duke Clinical Research Institute (DCRI) is uniquely positioned to serve as the ECHO CC after successfully serving as the ECHO CC for the last seven years. In addition, DCRI manages >30 active network and administrative coordinating centers and has emerged as a leader in pediatric research. Unique features of the proposed ECHO CC include: 1) extensive experience and track record of the leadership team in the support of the initial ECHO Program and conduct of multiple pediatric studies; 2) pediatric operational expertise of the DCRI; and 3) existing, robust administrative infrastructure necessary to effectively and efficiently manage responsibilities for coordinating the ambitious efforts of the ECHO Program. The team is led by Drs. P. Brian Smith and Linda Adair. Dr. Smith is a neonatologist and an accomplished pediatric researcher and leader of networks. He served as PI of the ECHO CC since its inception seven years ago. Dr. Adair is internationally renowned for leadership of long-term pediatric cohort studies. Dr. Adair has been instrumental in multiple leadership roles in the ECHO Program over the last six years including oversight of the ECHO Opportunities and Infrastructure Fund (OIF), and roles in protocol development and implementation, training, and publications. The specific aims for the ECHO CC are to: 1) provide organizational infrastructure to coordinate and oversee ECHO Program's research activities; 2) support ECHO Cohort Committees and communication among all ECHO Program Components and stakeholders; 3) manage the ECHO OIF and foster training of a diverse cohort of investigators through an inclusive research environment. The ECHO CC will establish and oversee the required infrastructure to coordinate the multiple levels of membership in the ECHO Program. This infrastructure will focus on methods of learning valuable information about environmental exposures through aggregation of massive amounts of data from ECHO Cohort Study Sites. The ECHO CC will make scientific efforts faster and more efficient while protecting human subjects. This infrastructure is possible because of the expertise of DCRI, which not only has extensive experience in coordinating pediatric studies but also has the essential platforms ready.

OVERALL PROJECT NARRATIVE Well-designed research is urgently needed to examine the impact of environmental exposures on health outcomes in children. The Duke Clinical Research Institute (DCRI) proposes to leverage its resources as the world's largest academic research organization to continue its success serving as the administrative hub and Coordinating Center of the Environmental influences on Child Health Outcomes (ECHO) Program.