Dear Matt: The people who are actively working with this whom I know are Genady Lyubeznik and Manuel Blickle. The key point seems to be that certain $R[F]$-modules become simpler when viewed as $D_R$-modules (here $F$ is the Frobenius). It has been applied to show that certain local cohomology modules over regular local rings in positive characteristic have finitely many associated primes. Examples are in the following papers:
D-module structure of R[F]-modules and
Generators of D-modules in positive characteristic
D-module structure of R[F]-modules, Trans. Am. Math. Soc 355 (2003), 4, 1647–1668, and
Generators of D-modules in positive characteristic, Math. Res. Lett. 12 (2005), no. 4, 459–473,
and the references there intherein. There is also this new preprint, Lyubeznik, Zhang and Zhang, preprintA Property of the Frobenius Map of a Polynomial Ring, which might be of interest.