The Spartans are 10th in the nation, allowing just 86 yards rushing per game. Opponents are averaging three yards a carry and have run for scores just twice in six games.
Though Michigan State let Indiana score the first 17 points of last week's game, its defense adjusted to the quick tempo set by the Hoosiers and rallied for a 31-27 victory.
For all Indiana could do through the air, it rushed for just 35 yards.
"To come back in that game, there were going to be one of two statements made. Either it was going to be negative or positive at the end of the game. And we took the positive route," Michigan State coach Mark Dantonio said.
The extra week also gave the Hawkeyes more time to shore up a passing game that's been a disappointment much of this season.
Iowa has shown slow but somewhat steady improvement over the past few weeks, culminating in Vandenberg's steady 192-yard performance, one-touchdown performance against the Gophers.
But Vandenberg has been sluggish on the road, as Iowa won just one road game in 2011 away from Kinnick Stadium.
With the Spartans likely to focus on Weisman, the onus will be on Vandenberg and his skilled but inconsistent receiving corps to take advantage.
"When you play a really good defense, which Michigan State certainly is, you can't be one-dimensional in any way, on any down," Vandenberg said. "We've got to mix it up as much as possible to make sure they're not just teeing off on us."