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The president said in a statement that Jackson, a Navy rear admiral, "has seen firsthand the tremendous sacrifice our veterans make and has a deep appreciation for the debt our great country owes them."
Jackson, a longtime presidential physician, oversaw Trump's annual medical checkup, which he said "went exceptionally well." He also presided over Barack Obama's last physical in office in 2016.
Trump thanked Shulkin for his service and said Robert Wilkie will serve as acting secretary. Wilkie currently serves as undersecretary of defense for personnel and readiness at the Department of Defense.
Shulkin has been under fire after an internal watchdog report revealed that the VA had improperly approved taxpayers footing the bill for a trip Shulkin's wife took with him to Europe last year.
That same report found that Shulkin told a subordinate to handle personal plans for him and his wife during that trip, and that he improperly accepted tickets to the Wimbledon tennis tournament.
Dan Caldwell, executive director of Concerned Veterans for America, said in a statement that Shulkin "ultimately became a distraction from the important task of improving health care for our veterans."
"We are hopeful that this change will end the recent distractions at the VA and put the focus back on advancing policy that will ensure veterans get the health care and other benefits they have earned," Caldwell said.
Shulkin's departure comes on the heels of a series of exit announcements from the Trump administration in this month alone, including those by Secretary of State Rex Tillerson, National Security Advisor Director H.R. McMaster, National Economic Council Director Gary Cohn, Communications Director Hope Hicks, and Trump's personal aide John McEntee.
McMaster's resignation was announced March 22, just hours after John Dowd, Trump's lead lawyer for an ongoing probe of Russian interference in the 2016 presidential election, quit.
Shulkin was the only member of Trump's cabinet who was a holdover from the Obama administration. He has been engaged recently in a nasty intra-departmental fight with political appointees in the VA, a fight that has included him ceasing to use the VA's own spokesman as his contact for the media.
In addition to his own IG's report on his wife flying to Europe at taxpayer expense, Shulkin earlier this month was hit by another IG report that criticized the department for a series of failures at a big veterans' hospital in Washington.