PROJECT SUMMARY / ABSTRACT The goal of the Boston Children's Hospital K12 CHRCDA Program is to develop independent pediatrician physician-scientists who will decipher the pathobiology of childhood disease and develop transformative new therapies. Our Scholars will perform laboratory-based basic and translational research under the mentorship of outstanding scientists at Boston Children's Hospital and other affiliated institutions. Our program has been established to ensure the continued development of outstanding independent pediatrician-scientists in the field. In this proposal, we describe a program that includes intensive mentoring, a comprehensive didactic program, and appropriate supervision and support to ensure that our Scholars reach their maximum scientific potential. Programmatic oversight will be provided by an External Advisory Committee and an Internal Steering Committee. Plans are in place for programmatic self-evaluation and for review of Scholar Progress. We propose to continue the funding of three Scholar positions. Scholars will be funded for a minimum of two years, contingent on satisfactory progress on research and career development activities, and the overall pool of Scholar candidates. Scholars will be faculty members most often at the rank of Instructor, but Assistant Professors who are early in the development of their independent careers will also be eligible to apply. Scholars will be considered at any point from the beginning of their Instructorship until they are considered to be two years away from submitting their first R-level NIH grant or equivalent, though no more than four years beyond the end of fellowship training. Scholars will work in broad areas of scientific investigation relevant to child health. Past and present Scholars have studied the genomics of rare childhood disease, developmental biology, mucosal immunology, host- microbe interactions, monogenic kidney diseases, genetics of epilepsy, and environmental effects on early brain development. Our Scholars are expected to elucidate molecular mechanisms of disease, leading to the development of transformative new therapies for a broad range of diseases of childhood.