[3] O'Shea earned her Bachelor of Arts in biochemistry from Smith College in 1988 and her PhD in chemistry from MIT in 1992 at age 26[4][3] working with Peter S. Kim studying leucine zippers.

[4] During her postdoctoral fellowship, O'Shea worked with Robert Tjian and Ira Herskowitz studying chromatin regulation of transcription in yeast.

[5] When she was joined by her graduate school colleague Jonathan Weissman, they began to determine the location and abundance of all of the proteins in the yeast genome.

[6][7] After her PhD, O'Shea was briefly a Basic Research Fellow before joining the faculty of University of California, San Francisco as an assistant professor in 1993.

[9] During her presidency, in 2025, HHMI cancelled their Inclusive Excellence 3 (IE3) program, which was a 6-year (2022-2028) $8.8 million award they had committed to the IMPACT STEM Network, which sought to enhance undergraduate science education and research, following incoming President Donald Trump’s administration elimination of programs devoted to diversity, equity, and inclusion across all U.S. scientific agencies.