Researcher

Thomas Lindahl

Profile

Thomas Lindahl is a Swedish-British biochemist at The Francis Crick Institute who shared the 2015 Nobel Prize in Chemistry with Paul Modrich and Aziz Sancar for their mechanistic studies of DNA repair. Lindahl's pioneering contribution was the discovery of base excision repair (BER)—a DNA repair pathway that corrects the spontaneous chemical damage to DNA bases that occurs thousands of times per day in every cell. His seminal insight was that DNA is intrinsically unstable and that cells must continuously repair it to maintain genetic integrity. He purified the first mammalian DNA glycosylase enzymes and reconstituted the entire BER pathway in vitro. The BER pathway removes oxidized, alkylated, and deaminated DNA bases, and its dysfunction contributes to cancer, neurodegeneration, and aging. Lindahl's work established the molecular basis for the synergy between chemotherapy agents that damage DNA and inhibitors of DNA repair (e.g., PARP inhibitors, which target the BER pathway). PARP inhibitors are now approved for BRCA-mutated ovarian and breast cancers, and the rational exploitation of BER inhibition in cancer therapy owes much to his foundational biochemistry.

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