Columbia University’s medical school announced on Thursday that one of its graduates was donating $400 million, the largest gift in the medical school’s history.

The gift, from P. Roy and Diana Vagelos, would expand biomedical research at a school that already bears their name, after they donated $250 million in 2017.

It comes at a critical time for the university, which spent much of the last school year convulsed by protests over the Israel-Hamas war. The university’s handling of those protests led some major donors to pause their contributions to the school.

Last week, the university’s president, Nemat Shafik, stepped down from her job, and was replaced in the interim by Dr. Katrina Armstrong, the chief executive of Columbia University Irving Medical Center, which includes the medical school.

In an interview on Thursday, Dr. Armstrong said that the Vagelos gift should not be viewed in the context of the protests and controversy that defined university life over the past year.

“This gift has been fundamentally focused on driving science and driving our impact, in our mission,” Dr. Armstrong said. “That is their singular focus,” she said of the Vageloses.