The research focus of the Rizzo laboratory is on DNA damage. My laboratory studies the chemical mechanism by which electrophiles react with DNA to form DNA adducts and their subsequent enzymatic processing (replication and repair). We utilize the tools to synthetic chemistry to incorporate the lesions of interest into oligonucleotides in a sequence-specific manner. We then utilize the tools of biochemistry to examine how the lesions affects replication fidelity by DNA polymerases and the recognition of the lesion by DNA repair proteins. NMR and crystallographic methods are used in collaboration with other laboratories to determine the structural perturbation caused by the lesions. The relationship between structure and DNA processing is a central theme of the research program. Current projects involve DNA lesions derived from heterocyclic aromatic amines found in cooked meats, endogenous bis-electrophiles from lipid peroxidations (acrolein and 4-hydroxynonenal) and the degradation of carbohydrates (methylglyoxal), and DNA damaging agents used in chemotherapy (methylating agents and nitrogen mustards). We have a long-standing interest in bis-electrophiles that can form interstrand DNA cross-links and DNA-protein cross-links. The Rizzo laboratory is associated with the NIEHS supported Center in Molecular Toxicology (of which Prof. Rizzo serves as Co-Deputy Director and Leader of the DNA Damage and Genetic Instability Research Core), the NCI supported Vanderbilt-Ingram Cancer Center, and the Vanderbilt Institute for Chemical Biology.