PROJECT SUMMARY The proposal describes a five-year mentored laboratory training experience designed to lead to an independent academic career in genomic medicine. The applicant holds M.D. and Ph.D. degrees, and is certified by the American Board of Internal Medicine and American Board of Medical Genetics and Genomics. The applicant seeks to become a human geneticist and to make significant contributions to the field of personalized medicine within the adult patient population. The applicant’s long-term goal is to practice as a physician scientist with an independently funded laboratory at an academic institution. The proposed research builds upon skills developed during the applicant’s prior research and training. The applicant has built a career development and research plan that will form a foundation for her transition to an independent position. The first 2 years of the career development award will focus on formal coursework, patient recruitment, and phenotyping. The final 3 years of the career development award will focus on implementation of skills attained and analysis of genomic data. Discoveries during this time will form the foundation of an R01 proposal. The career development plan includes training designed to broaden the applicant’s scientific skillset, including coursework in statistical genetics, bioinformatics, and genetic epidemiology, as well as training that will prepare her in leadership, mentorship, grant writing, and the ethical implications of genomic research. Implementation of these skills within her research plan will enable experiential learning. Seminars, grant- writing workshops, journal clubs, laboratory and research meetings, and presentations at national and international meetings will provide additional opportunities to develop and strengthen skills. The mentor, Dr. James R. Lupski, is a leader in the field of genomic medicine, with >500 publications to date and a superb record of training physician scientists. The proposed advisory committee includes Dr. Suzanne Leal, Dr. David Wheeler, Dr. Sharon Plon, and Dr. Chad Shaw, all experts in their relative fields who will provide scientific and career guidance and oversee development of the proposed skillsets. The mentor and advisory committee will meet regularly with the applicant to ensure that scientific and career development goals are being met, and to offer their individual expertise relevant to the proposed research. The research environment provides an outstanding intellectual environment, and state-of-the-art genomic sequencing and analysis technology will be available to the applicant. The institution and the department are fully committed to the applicant’s success. The proposed research seeks to identify the genetic architecture underlying adult-onset disease. The applicant proposes that the molecular contribution to adult disease is not fully understood, and that a significant proportion of adult-onset disease is caused by germline or de novo mutation...