While in the U.S. House of Representatives, Wilson focused on national security issues, serving on the United States House Permanent Select Committee on Intelligence and the United States House Committee on Armed Services. She also focused on health care, energy, manufacturing and trade, and telecommunications, serving on the United States House Committee on Energy and Commerce. She opted not to run for re-election in 2008 and sought the U.S. Senate seat of retiring Senator Pete Domenici but finished second in the Republican primary to Congressman Steve Pearce, who then lost the general election to Democrat Tom Udall. On March 7, 2011, she announced another run for Senate in 2012 to replace retiring Senator Jeff Bingaman, but lost the general election to Martin Heinrich, her successor in the House of Representatives.
In April 2013 she was selected to be President of the South Dakota School of Mines and Technology by the South Dakota Board of Regents. She was the eighteenth president, and first female president, of SD Mines. On January 23, 2017, President Donald Trump announced that he would nominate Wilson as Secretary of the Air Force. The US Senate confirmed her nomination on May 8, 2017.
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