In 1974, he was offered a position at MIT by Biologist Salvador Luria. He was Director of MIT's Center for Cancer Research (now the Koch Institute for Integrative Cancer Research) from 1985 to 1991; head of the Biology department from 1991 to 1999; and Director of the McGovern Institute for Brain Research from 2000 to 2004. He is currently a professor of Biology and member of the Koch Institute, and has been an Institute Professor since 1999. Sharp co-founded Biogen, Alnylam Pharmaceuticals, and Magen Biosciences, and has served on the boards of all three companies.