Tilghman, 66, announced her intentions in an email Saturday to students, faculty, staff and alumni. She informed university officials of her plans a day earlier.
"There is a natural rhythm to university presidencies," Tilghman wrote in her statement to the university community. "With the major priorities accomplished or well on their way to being realized ... it is time for Princeton to turn to its 20th president to chart the path for the next decade and beyond."
Tilghman, who became the Ivy League school's 19th president in 2001, will leave office in June. She then plans to take a year's leave before returning to teaching at Princeton. She is considered a leader in the field of molecular biology.
A search committee - led by Kathryn A. Hall, chairwoman of the university's Board of Trustees - will be named to choose Tilghman's successor. A time frame for its decision has not been determined. The panel will include several board members and four faculty members, as well as student and staff representatives.
"Shirley Tilghman has provided exceptional leadership for Princeton over these past 11 years, building on its distinctive strengths and pioneering important new initiatives in areas ranging from neuroscience, energy research and the arts to internationalization and campus life, while also providing national leadership on a broad range of issues," Hall said. "We are deeply grateful for her service as president, and we are very pleased that she will remain a member of our faculty."
A native of Canada, Tilghman came to Princeton in 1986 as a professor and later chaired the university's Council on Science and Technology, which encourages the teaching of science and technology to students outside the sciences. University officials also honored her with the President's Award for Distinguished Teaching in 1996.
When Tilghman's predecessor, Harold T. Shapiro, announced his intentions to step down, she initially was elected by faculty members to serve on the search committee that was to pick his successor. But she was eventually asked to leave the committee so she could be considered for the presidency. She was chosen for the post in May 2001, and assumed office the following month.
During Tilghman's tenure as president, the school greatly increased the number of students on financial aid and more than doubled the average aid they receive. She also is credited with overseeing the advancement of several major initiatives, including expanding the undergraduate student body, the construction of new performing arts, neuroscience and library facilities and drafting a master plan to chart the future development of the school.
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