Lisa Jackson, administrator of the Environmental Protection Agency, announced Thursday that she is resigning.

"I will leave the EPA confident the ship is sailing in the right direction, and ready in my own life for new challenges, time with my family and new opportunities to make a difference,'' Jackson said in a statement.

Jackson's four-year tenure included clashes with industry and congressional leaders over issues, such as global warming, the Keystone XL oil pipeline and coal-fired plants.

In a statement, Obama praised Jackson. "Over the last four years, Lisa Jackson has shown an unwavering commitment to the health of our families and our children,'' he said. "Under her leadership, the EPA has taken sensible and important steps to protect the air we breathe and the water we drink, including implementing the first national standard for harmful mercury pollution, taking important action to combat climate change under the Clean Air Act, and playing a key role in establishing historic fuel economy standards that will save the average American family thousands of dollars at the pump,while also slashing carbon pollution."

Reaction to the announcement was swift.

“There has been no fiercer champion of our health and our environment than Lisa Jackson, and every American is better off today than when she took office nearly four years ago,'' said Frances Beinecke, president of the Natural Resources Defense Council. "For that, we are deeply grateful to Lisa for her service, and to President Obama for having appointed her to this vital position."

Larry Schweiger, president and CEO of the National Wildlife Federation, called Jackson one of the most effective leaders in the history of the EPA.

"Her legacy will be cleaner air for all Americans, and she has set the Environmental Protection Agency on a new course to tackle climate change by establishing the first standards to reduce carbon pollution from smokestacks and tailpipes,'' he said. "We thank her for her exceptional service and wish her well.”

As he launches his second term, Obama must fill a number of key vacancies. While Obama’s Cabinet remained relatively stable in his first term, several senior aides left. Political observers expect half of the president’s Cabinet – as well as a handful of senior staffers – to change at the start of his second term, as has been the nature of life and work at the White House. Former Presidents George W. Bush and Bill Clinton each replaced half of their Cabinets after they were re-elected.