"Right now, Washington is filled with too many people more interested in getting rich or getting on camera than getting things done for you," Murphy says in a campaign launch video, as footage of DC lawmakers, including Menendez, appear on screen.
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Murphy, 58, has never run for office herself but is widely regarded as a skilled politico and accomplished advocate in her own right. She is expected to benefit from the connections she has built alongside her husband, Democratic Gov. Phil Murphy, who is currently in his second and last consecutive term, which runs through 2026. If elected, she would become the Garden State's first female US senator.
In her announcement video, Murphy highlighted her efforts as first lady to reduce maternal mortality in New Jersey and to include climate change education in school curriculum.
"I'm so proud of everything we've accomplished," she says. "But I know there's a lot more to do."
In response to Murphy's announcement, Menendez released a lengthy statement, part of which says:
"I'll gladly put up my record of success on behalf of the people of New Jersey against anyone, and am confident that when all the facts have been presented and my innocence proven, I'll continue to do what I've always done for the past 30-plus years: deliver results for the people of New Jersey."
Political scholar Kelly Dittmar with Rutgers University says a first lady running for Senate isn't very common, and it could work for her or against her.
"New Jersey is a state that has never elected a woman to the U.S. Senate, and so if she were to be successful it would break a particular glass ceiling in our state in terms of representation of women," Dittmar said.
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A number of Democrats in New Jersey and Capitol Hill, most notably US Sen. Cory Booker, have called for Menendez to resign rather than seek reelection. Even without the longtime incumbent in the race, the primary is expected to be divisive, pitting the state's powerful political machines against grassroots and liberal groups eager to break their grip on power. Most observers expect Murphy to have the backing of county leaders. Kim recently won the endorsement of the influential progressive group SOMA Action.
The early move by the progressive group to back Kim underscored the stakes of the race and, potentially, the challenges Murphy could face in seeking to move from Trenton to Washington.
"Our members want bold leadership that answers to the people, not the party bosses," SOMA Action President Jessica James said in a statement announcing her group's endorsement. "We think voters across the state feel the same.
Murphy's candidacy - for the Democratic Senate nomination in a deep-blue state - is particularly remarkable given her past association with Republican politics. She voted for years in GOP primaries and donated to candidates from both parties, including during the time her husband spent as the Democratic Party's national finance chair.
Asked during his first run for governor why she shifted, Murphy said it had been a slow process.
"Over time, in talking to people, they would say, 'What concerns you?' Or 'What are you passionate about?' And I would say: 'Well, I'm pro-choice, I'm anti-guns, I'm pro-environment,'" Murphy told NJ.com in 2017. "It was pointed out to me along the way, 'You know, if you want to find a label, you are in fact a Democrat.' And I said, 'Oh, OK.'"
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Early support for Kim and other high-profile names rumored to be considering bids could pose a greater threat to Murphy's hopes than Menendez, if he decides to seek a fourth full term. Despite his deep roots and connections across the state and a history of beating back corruption charges, the incumbent now stands accused of bribery, extortion and acting as an agent to advance the interests of the Egyptian government.
One Republican has announced a campaign: Christine Serrano Glassner, mayor of Mendham in North Jersey.
Congressman Jeff Van Drew is said to be exploring a run but hasn't decided yet.
A Republican hasn't been elected to a senate seat in New Jersey since 1972.
Political activist Larry Hamm has also announced that he's running for the seat on the Democratic ticket. This will be his second run.
The CNN Wire contributed to this report.