Laboratory of DNA damage and repair and DNA-targeting drugs
Our research program aims to gain molecular-level insights into the mechanisms of DNA damage, repair, mutagenesis, translesion synthesis, and DNA-targeting anticancer drugs. We are particularly interested in oxidative (e.g., 8-halogenated guanine, 8-oxoguanine) and alkylative (e.g., N7-alkylguanine, intra- and interstrand cross-links) DNA lesions that are formed by a wide variety of mutagens (e.g., reactive oxygen or halogen species), carcinogens (e.g., nitrosamines, ptaquiloside) and chemotherapeutics (e.g., nitrogen mustards, platinum-based drugs). Our research questions include: How do oxidative or alkylative DNA lesions affect DNA structures and base pairing properties? What are the mechanisms by which DNA repair machineries (e.g., base and nucleotide excision DNA repair, interstrand cross-link repair) recognize and process their substrate lesions? How do translesion synthesis DNA polymerases (e.g., polη, polβ) accurate or promutagenic bypass of DNA lesions? How do DNA lesions induce mutagenesis and carcinogenesis? What are the molecular mechanisms by which mono-functional platinum-based chemotherapeutics induce cancer cell death? We utilize combined tools of synthetic chemistry, biochemistry, and structural, cellular and molecular biology to address these questions.