HARRISBURG, Pa. (AP) — For most of his 30 years as Pennsylvania’s longest-serving U.S. senator and prominent moderate in Congress, Arlen Specter was a Republican, though often at odds with the GOP leadership.

He helped end the Supreme Court hopes of former federal appeals Judge Robert H. Bork, who was nominated by Ronald Reagan. Decades later, he was one of only three Republicans in Congress to vote for President Barack Obama’s stimulus.

His breaks with his party were hardly a surprise: He had begun his political career as a Democrat and ended it as one, too.

In between, he was at the heart of several major American political events. He rose to prominence in the 1960s as an assistant counsel to the Warren Commission, developing the single-bullet theory in President John F. Kennedy’s assassination. He came to the Senate in the Reagan landslide of 1980 and was a key voice in the confirmation hearings of both Bork and Clarence Thomas.

Specter died Sunday died at his home in Philadelphia from complications of non-Hodgkin lymphoma, said his son Shanin. He was 82. Over the years, Specter had fought two previous bouts with Hodgkin lymphoma, overcome a brain tumor and survived cardiac arrest following bypass surgery.

Intellectual and stubborn, Specter took the lead on a wide spectrum of issues and was no stranger to controversy.

In one of his last major political acts, Specter startled fellow senators in April 2009 when he announced he was joining the Democrats. He said he was “increasingly at odds with the Republican philosophy,” though he said the Democrats could not count on him to be “an automatic 60th vote” that would give them a filibuster-proof majority.

He had also concluded that he was unlikely to win a sixth term as a Republican, and his frankness about why he returned to the Democratic Party was packaged in a powerful TV ad by his primary opponent, then-U.S. Rep. Joe Sestak, who hammered away at the incumbent as a political opportunist.

“My change in party will enable me to be re-elected,” Specter says in TV news footage used in the ad.

The announcer ends the ad saying, “Arlen Specter changed parties to save one job — his, not yours.”

And Democrats picked Sestak, a retired Navy vice admiral, over Specter in the 2010 primary, ending his decades of service. Sestak lost Specter’s seat to conservative Republican Rep. Pat Toomey in the general election by 2 percentage points.

Specter rose to prominence in the 1960s as an aggressive Philadelphia prosecutor and during his time on the Warren Commission.

In 1987, Specter helped thwart Bork’s nomination to the Supreme Court, earning him conservative enemies who still bitterly refer to such denials as being “borked.” But four years later, Specter was criticized by liberals for his tough questioning of Anita Hill at Clarence Thomas’ Supreme Court nomination hearings and for accusing her of committing “flat-out perjury.” The interrogation, televised nationally, incensed women’s groups and nearly cost him his seat in 1992.

Specter took credit for helping to defeat President Bill Clinton’s national health care plan — the complexities of which he highlighted in a gigantic chart that hung on his office wall for years afterward — and helped lead the investigation into Gulf War syndrome, the name given to a collection of symptoms experienced by veterans of the war that include fatigue, memory loss, pain and difficulty sleeping. And following the Iran-Contra scandal, Specter pushed legislation that created the inspectors general of the CIA, which later exposed Aldrich Ames as a Soviet spy.

But he was not afraid to buck his fellow Republicans.

As a senior member of the powerful Appropriations Committee, Specter pushed for increased funding for stem-cell research, breast cancer and Alzheimer’s disease, and supported several labor-backed initiatives in a GOP-led Congress. He also doggedly sought federal funds for local projects in his home state.