Steve Karlen's research centers around the conversion of lignocellulosic biomass to commodity chemicals and liquid fuels. His primary focus is the phenolic fraction of the biomass found in the soluble metabolites (extractables) and as part of the plant cell wall. The largest fraction of these phenolic molecules is the lignin. Leveraging his background in synthetic organic chemistry, analytical instrumentation, and organic materials, he works on developing economically viable processes that add the production of commodity chemicals to an array of biorefinery platforms.

Some of his other bioenergy research interests include the identification of unknown compounds generated by chemical deconstruction of plant biomass, linking variations in lignin composition across the plant kingdom to the evolution of associated lignin biosynthesis genes, and utilizing microbes to funnel complex phenolic product mixtures to high value commodity chemicals.