Dr. O'Toole was confirmed in November 2009 as the Under Secretary for Science and Technology at the Department of Homeland Security. From 2003 to 2009, Dr. O'Toole was the CEO and director of the Center for Biosecurity at the University of Pittsburgh Medical Center (UPMC) and a professor of medicine and of public health at the University of Pittsburgh. Prior to founding the UPMC Center in 2003, Dr. O'Toole was one of the original members of the Johns Hopkins Center for Civilian Biodefense Strategies and served as its director from 2001 to 2003.

Dr. O'Toole is internationally known for her work on biosecurity and on health and safety issues related to the U.S. nuclear weapons complex. From 1993 to 1997, she served as Assistant Secretary of Energy for Environment Safety and Health, overseeing the health and safety of the approximately 100,000 workers in the U.S. nuclear weapons complex and Department of Energy (DOE) laboratories. She developed the first overall management and safety plan for dealing with the highly enriched uranium, plutonium, spent fuel, and radioactive waste left in place when nuclear weapons production was stopped in the early 1990s. She ran the multi-agency, multimillion dollar task force that oversaw the government's investigations into human radiation experiments conducted during the Cold War. And she led the U.S. delegation to Russia to establish the U.S./Russia cooperative effort to study radiation exposure and environmental hazards of the Russian nuclear weapons complex.

Prior to her work at DOE, Dr. O'Toole was a senior analyst at the Congressional Office of Technology Assessment (OTA) and also served as a consultant to industry and government. She has served on numerous government and expert advisory committees dealing with biodefense and has published widely in the biodefense field. She is coeditor-in-chief of the journal Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science. She was also a principal author and producer of biosecurity excercises Dark Winter and Atlantic Storm in 2001 and 2005, respectively.

Dr. O’Toole has a bachelor's degree from Vassar College, an MD from the George Washington University, and an MPH from Johns Hopkins University. She completed internal medicine residency training at Yale and a fellowship in occupational and environmental medicine at Johns Hopkins University. She is board certified in internal medicine and in occupational and environmental health.