Establishing the Center for Molecular Epidemiology, Center for Biomedical Research Excellence (COBRE) has transformed research in the field of molecular epidemiology at Dartmouth. As the only Center for Molecular Epidemiology in northern New England, and one of the only COBRE programs nationally with this focus, we have successfully recruited and mentored early career investigators who are now becoming independent in their careers. They represent the new generation of investigators in this emerging area of research both regionally and nationally. In doing so, we have expanded our research productivity and grant portfolio, as evidenced by a growing number of publications and grants awarded. In addition to their independent grant submissions, our tight-knit group of investigators catalyzed a number of major initiatives and interdisciplinary grant opportunities by leveraging Center resources. These achievements include creating a Department of Epidemiology, increasing program and center award support, and attaining innovative cross-disciplinary training grants. As part of this Phase II application, we proposed to progress our Center towards sustainability by further enhancing recruitment, career development, and engagement of talented junior investigators. We will bring together this enlarging group of diverse faculty with shared interests in integrating and translating cutting edge scientific technologies and discoveries to improve our understanding of major human health concerns. Such efforts are crucial for directing clinical decisions, public health policies and practice change. We will strengthen our vibrant molecular epidemiology research infrastructure from which innovative methods can be applied and new discoveries can be translated. Specifically, we will add four new independent research projects with intertwined themes that are supported by our state-of-the-art Biorepository Core created in Phase I. Through our effective Administrative, Career Development, and Research Integration Core, we will offer a Pilot Program to incentivize pioneering research and regional partnerships. These essential components will allow us to achieve our goals of: (1) stimulating rigorous innovative research and fostering the career development of junior investigators and recruiting new faculty and members to our Center, (2) promoting translation of novel technologies and basic research findings on common pathways of disease etiology and progression, and (3) informing strategies to prevent human disease throughout the lifespan. Our success in Phase I combined with strong institutional support, positions us to serve as a vital resource in molecular epidemiology for northern New England, COBRE and IDeA Networks of Biomedical Research Excellence (INBRE) programs regional and nationally, and for cultivating molecular epidemiology more broadly. We propose to continue a translational biomedical research center that fosters investigations that apply cutting- edge innovations to illuminate the causes of human diseases. As such, our Center has the potential to change practice and reduce disease burden throughout the lifespan. Our COBRE Center for Molecular Epidemiology at Dartmouth provides a unique and critical resource from which to grow the next generation of scientists, for COBRE/INBRE programs regionally and nationally, and for molecular epidemiology more broadly.