David Eisenberg and his research group focus on protein interactions. In their experiments they study the structural basis for conversion of normal proteins to the amyloid state and conversion of prions to the infectious state. In computational work, they derive information on protein interactions from genomic and proteomic data, and design inhibitors of amyloid toxicity.

In 2005, they determined the atomic-level structure for the spine of an amyloid fiber. This structure shows that the spine consists of two parallel beta sheets, packed across a tight, dry interface which is called as steric zipper. The structure of the spine explains the stability of amyloid, gives hints about the conversion process, and suggests why some proteins form amyloid while others do not. 

Their goals are to understand the general features of the conversion to the amyloid state, why some of the diseases are transmissible between organisms, what are the structures of the toxic units, and how they exert their toxic actions.