Dr. DeSalle works in molecular systematics, microbial evolution, and genomics. His current research concerns the development of bioinformatic tools to handle large-scale genomics problems using phylogenetic systematic approaches. Dr. DeSalle has worked closely with colleagues from Cold Spring Harbor Labs, New York University, and the New York Botanical Garden on seed plant genomics and development of tools to establish gene family membership on a genome- wide scale.

His group also focuses on microbial genomics, taxonomy, and systematics. In particular, they approach tree-of-life questions concerning microbial life using whole genome information. He also dabbles in Drosophila systematics.