Dr. Thomas Spratt's research has focused on the elucidation of mechanisms of DNA damage, repair and mutagenesis. The Spratt lab uses a multidisciplinary approach including organic synthesis, steady-state and transient state kinetics, protein engineering, cell biology, mass spectrometry and next-generation sequencing.

The Spratt lab has made contributions in elucidating mechanisms of tobacco carcinogenesis. They have identified repair pathways and mutagenesis mechanisms of specific DNA adducts produced from tobacco smoke.

The Spratt Lab uses a chemical biology approach, in which modified nucleotides are designed and synthesized to elucidate specific aspects of the active site chemistry of DNA repair proteins and polymerases. In early work, the mechanism of action of O6-alkylguanine –DNA alkyltransferase, a critical DNA repair protein, was examined. More recently, critical protein-DNA and DNA-DNA interactions during the replication of undamaged and carcinogen-damage DNA have been identified.

Current research involves designing polymerase-specific substrates to probe the multi-faceted roles of translesion DNA polymerases in vivo.