James R. Lupski was born and raised on Long Island, New York, one of eight children. He attended a Roman Catholic elementary school but a public high school. Lupski and three of his siblings manifested, at different times and to different degrees, Charcot-Marie-Tooth disease (CMT); James's disease was serious enough to require several surgeries when he was in high school, surgeries that kept him at home for much of his high school years. He became interested in his disease and in genetics and decided he wanted to become a doctor. He also became a professional chess player. He won a full scholarship to New York University (NYU), where he majored in chemistry and biology and minored in mathematics and psychology. In David Schuster's laboratory he tried to isolate brain receptors; and during his summers he worked at Cold Spring Harbor Laboratory, learning to clone genes. Accepted early to NYU Medical School, Lupski then won acceptance to the MD/PhD program. He wrote his doctoral thesis on the macromolecular synthesis operon. The discovery of the gene associated with Huntington's disease inspired him to search for the CMT disease gene. He was courted by Baylor College of Medicine, where he was given a faculty appointment while he was still an intern. At Baylor he set up his own lab and began his research into the genetics of CMT, studying a large family in Louisiana. Lupski eventually patented a diagnostic test for CMT and continues his research on the disease. Lupski continues to teach, to manage his lab, to publish, to consult for private industry, to take out patents, and to balance work and family life with his wife and two daughters.