Republicans got a wake-up call regarding the perils of anti-incumbent primaries last year, when Alabama Sen. Luther Strange lost a runoff to Roy Moore, who in turn lost to Democrat Doug Jones – at one time an unthinkable outcome. But not everyone sees danger. Instead, another conservative insurgent from the Deep South, Mississippi state Sen. Chris McDaniel, is poised to run against a fellow Republican, U.S. Sen. Roger Wicker.

McDaniel is expected to announce a bid for the seat at a Wednesday rally in his hometown of Ellisville, Miss., the eve of the March 1 filing deadline. “Most conservatives feel that our party, the Republican Party, has lost its foundation," McDaniel said during a Facebook Live video promoting the rally. "We're looking for a fight, and I can't wait to have you on my team again."

But the challenge comes as Republican lawmakers and President Trump are getting along quite well. The party passed a long-awaited tax bill in December that GOP incumbents plan to use as a calling card in the midterms. Steve Bannon, the former Trump adviser who had planned to back anti-incumbent campaigns around the country, is no longer in the president's good graces, and therefore considered a pariah among Trump's base. And Republican Senate candidates around the country are taking pains to align themselves with the president.

Trump pledged his support to Wicker on Twitter Tuesday ahead of McDaniel's announcement, calling the senator "a great supporter and incredible help in getting our massive Tax Cut Bill done and approved. Also big help on cutting regs. I am with him in his re-election all the way!"

McDaniel's bid will likely re-open party wounds and cause headaches for national operatives hoping to devote resources to open and Democratic-held seats. What’s more, the environment for taking down a party incumbent, particularly one who votes in line with the president, appears far less receptive than it did just a few months ago.

"We're generally an unsettled group of folks these days in America. But not everybody is disgruntled with every incumbent," said Mississippi Republican strategist Hayes Dent. "Universally, the disgruntled crowd is 100 percent with Trump. And Trump has already said he thinks Wicker has been doing a great job. So, what needle do you now need to thread if you're Chris McDaniel?"

The state senator’s supporters point to his challenge nearly four years ago to Sen. Thad Cochran, in which he forced the incumbent into a runoff. Cochran was considered the embodiment of the GOP establishment: a six-term senator who chaired the Appropriations Committee, a powerful post that symbolizes excess government spending for some conservatives. That primary became among the party's nastiest, involving nursing home spying and racial undertones. McDaniel eventually lost by about 8,000 votes, and challenged the results. He and his supporters argued the election was stolen from them, asserting that Cochran had mobilized black voters to turn out in the open primary. McDaniel has since embraced the hashtag "Remember Mississippi," which a super PAC supporting him took it as its name; it has raised $1 million in contributions.

"McDaniel is much more aligned with Mississippi's values than Sen. Wicker has demonstrated, which is going to be a big advantage for McDaniel," said Tommy Barnett, the super PAC's treasurer. "The people of Mississippi deserve to have a strong voice in Washington, D.C., fighting for them, not someone who goes along with the Republican establishment every chance they get. It's going to be a fight and we look forward to fighting alongside Chris McDaniel."

Challenging Wicker apparently wasn’t McDaniel's first choice. There has been wide speculation about Cochran's future in the Senate, given his ailments and missed votes. If he were to retire, Republican Gov. Phil Bryant would appoint a temporary stand-in, and the state would host an open race in November. McDaniel had been eyeing that pathway, but with no movement on Cochran's part, and the March 1 deadline fast approaching, he has set his sights on Wicker.

The Wicker camp wasn't caught off guard. "We've been planning for this for a year and we're ready," said campaign spokesman Justin Brasell. "Senator Wicker is helping President Trump get his agenda passed. We feel like we're in great shape."

Unlike some of his Senate colleagues, Wicker has been a steadfast supporter of the president, who is widely popular in Mississippi. In October, when there were questions about the president's loyalty to party members, Politico reported that Trump promised to back Wicker. Vice President Mike Pence has donated to his campaign. And Wicker, who chaired the National Republican Senatorial Committee in 2016, has raised over $4 million. His campaign also released two new ads this week: one touting his work for veterans and another promoting an endorsement from state Sen. David Parker, who backed McDaniel in 2014.

Nonetheless, McDaniel allies see areas of vulnerability for the incumbent. The two-term senator hasn't really faced a tough race before. He was appointed to the Senate in 2007 from the House to replace Trent Lott, and won a special election to the seat the following year. He was re-elected easily in 2012.

McDaniel is likely to make his campaign against Wicker a campaign against Senate Majority Leader Mitch McConnell, positioning himself to the right of Wicker and also as an ardent ally of Trump. But the Mississippi race has its own nuances that make it difficult to attach lessons from Strange’s loss in neighboring Alabama. For example, Strange had been appointed by a disgraced governor, which played into the electorate's decision. Elsewhere, Arizona Sen. Jeff Flake's criticisms of Trump invited a primary challenge this year; when it became clear he wouldn't survive, he decided to retire.

Asked in October how he would argue that Wicker was, in his view, insufficiently conservative despite voting with Trump, McDaniel told RCP that the president "was an agent of change. ... Sometimes we disagree. But as long as he is pushing back against Washington, D.C., and against the establishment … what we’re really after here is to change Washington.”

The anti-Washington sentiment throughout the country "requires the incumbent to make clear there may be a problem with Washington, but I'm not part of the problem," said Dent, the state GOP strategist.

"[McDaniel] has got a following, make no bones about that," he said. "I'm just not sure that following translates to a reasonable showing in a GOP primary right now in an age where President Trump supports Wicker."