According to a university release, Sheri Everts, who has been chancellor since 2014, will leave the post effective Friday.
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"Over the last few months, I have been experiencing significant health challenges, and I must now focus on my personal health and wellbeing," Everts said in a message to students, faculty and staff.
During Everts' tenure, enrollment grew at Appalachian State by nearly 16% to over 21,000, meaning the school has the fifth largest population among the 17 in the public university system.
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The release credited Everts for securing over $550 million for capital projects, with state-of-the-art residence halls and academic and athletics facilities.
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A new Appalachian State campus in Hickory builds on the school's "commitment to public service, and generations of North Carolinians will find great opportunity close to home because of Chancellor Everts' vision," UNC System President Peter Hans said in the release. "I'm very grateful for her devoted service."
According to the school, Hans said he would announce an interim chancellor by Friday. The UNC Board of Governors ultimately approves a permanent replacement.
Everts' time as chancellor also marked when the Appalachian State Faculty Senate approved in 2020 a no-confidence resolution against her. Resolution supporters cited issues with university finances, faculty morale and how the school handled the COVID-19 pandemic.
The Associated Press contributed to this report.