"It's like we've divided the country into pieces," the potential 2020 Democratic presidential contender told a gathering of U.S. mayors. "How can we be one America if we continue down this road?"
He said that the country longs to be united and that he was proud to have worked with Republicans during the course of his career. Biden also conveyed a sense of optimism about the path ahead.
"I think we've got to start believing in our people again. We're tougher than we think we are," he said at the U.S. Conference of Mayors' winter meeting. "We're looking to be led."
Biden said the story suggested that "one of my problems, if I ever run for president, is I like Republicans. Bless me father, for I have sinned," he told the city leaders, drawing chuckles and applause.
Biden said Upton as one of a handful of Republicans to vote for a major cancer research bill in 2017. Biden and his wife, Jill, head the Biden Cancer Initiative to accelerate development of cancer prevention and cures.
"We're in a situation now where this is a pretty dysfunctional town," Biden said. "We have different philosophies, but we want to get things done."