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UC San Francisco announced Wednesday that it has received a stunning $500 million donation — the single largest gift in University of California history and one of the most generous gifts ever given to an American university.

The gift, which comes at a time of dwindling financial support from the state, was pledged by the family foundation of the late Helen Diller, a San Francisco native and longtime champion of UCSF whose husband, Sanford, founded the Prometheus Real Estate Group, a San Mateo-based commercial real estate firm.

“My mother believed in science — and she believed in health care,” said her daughter, Jackie Safier, 52, president of the Helen Diller Foundation board, a member of the UCSF Foundation Board of Overseers and president at Prometheus.

“She asked: ‘What type of institution can have the most impact on global health care in the world, for all of humanity?'” Safier said. “She believed UCSF would have an incredible impact, with the necessary resources.”

The donation is expressly aimed at supporting the faculty and students of UCSF, a campus dedicated solely to research and graduate-level education in the life sciences and health professions, with schools of medicine, dentistry, nursing and pharmacy. In one fell swoop, the gift will increase UCSF’s endowment, which currently stands at $2.25 billion, by nearly 18 percent.

The gift surpasses other recent donations to private powerhouses such as Stanford and Harvard. Nike’s Phil Knight gave $400 million to Stanford; hedge-fund manager John A. Paulson gave $400 million to Harvard.

The Diller donation is an exception to a growing trend of wealth being directed to just a few elite private universities. The endowments of the top 10 richest schools in the nation hold nearly a third of total cash and investments, and the top 40 schools account for two-thirds, according to a report published by Moody’s Investors Service. This helps the already-rich schools get richer, widening the gap in campus resources.

As a public school, UCSF — despite its world-class reputation — faces tough competition when recruiting faculty because of budget constraints.

The university also enrolls more low-income students than most private schools. About 85 percent of UCSF’s students need financial aid, and about half are the first in their family to go to college. Far fewer have parents with graduate degrees.

“She recognized that public universities don’t have the large endowments that private schools have,” Safier said. “She thought this type of investment was critical.”

The Diller gift is also noteworthy because it is largely “unrestricted,” which is unusual in academia. The vast majority of university gifts can be used only for donor-authorized purposes, such as supporting a particular program, field of research or constructing a new building.

“This commitment is extraordinary in both scale and structure, and comes at a time when fiscal challenges at the state and federal level are particularly pressing,” UCSF Chancellor Sam Hawgood said in a statement.

The previous record gift to UCSF came from philanthropists Joan and Sandy Weill, who last April donated $185 million to establish a new institute to speed the development of new therapies for diseases affecting the brain and nervous system, including psychiatric disorders.

The $500 million from the Diller foundation will be directed toward:

Faculty support: A $200 million endowment will help UCSF faculty rise into leadership positions, help the school recruit eminent senior faculty from other institutions, as well as boost talented junior faculty at the beginning of their careers.

Student support: A $200 million endowment will support students at UCSF’s four professional schools. It will allow many, including first-in-their-family college students, to finish school with less debt so they have more freedom to pursue life-changing work in their own communities.

An “Innovation Fund”: The final $100 million will create a fund for support of high-risk, high-reward research with potential global impact.

Diller, a Woodside resident who died in 2015, was born at Mount Zion Hospital, now part of UCSF, and grew up in San Francisco. The only daughter of Dora and William Samuels, who met and married in post-World War I Poland, her father was a clothing salesman who later became a shop owner.

She credited her parents with instilling the importance of giving back. “It’s never too late, too early, or too often to … make the world a better place,” she once said.

Diller attended San Francisco public schools and then UC Berkeley, where she met her husband and later helped him found the Prometheus Real Estate Group, which developed Bay Area commercial and residential properties. Prometheus built the twin towers at Cupertino City Center and more than 13,000 apartments in the Bay Area, Seattle and Portland, Oregon.

Her family foundation’s previously gave $35 million to support UCSF’s Comprehensive Cancer Center.

“Helen Diller was a tremendous friend to UCSF during her lifetime,” saidHawgood, “and this generous commitment builds on her already substantial legacy of giving.”