Paul Modrich is a distinguished American biochemist renowned for his transformative contributions to understanding cellular DNA maintenance mechanisms. He currently serves as the James B. Duke Professor of Biochemistry at Duke University Medical Center and has been an Investigator at the Howard Hughes Medical Institute since 1995. After earning his bachelor's degree in biology from the Massachusetts Institute of Technology in 1968, he pursued doctoral studies at Stanford University, where he received his PhD in biochemistry in 1973 amid groundbreaking discoveries in DNA replication. Modrich began his independent research career at the University of California, Berkeley in 1974 before joining Duke University's faculty in 1976, where he established his pioneering laboratory investigating DNA repair processes.
Dr. Modrich's seminal achievement was the discovery and biochemical characterization of the DNA mismatch repair system, a critical mechanism by which cells identify and correct errors introduced during DNA replication. His meticulous research demonstrated how methyl groups attached to DNA serve as molecular signals that guide repair proteins to excise mismatched base pairs, reducing DNA replication error rates by a factor of one thousand. This work provided the molecular explanation for how cells maintain genomic fidelity across generations and established the fundamental connection between mismatch repair defects and Lynch syndrome, the most prevalent form of hereditary colorectal cancer. For these paradigm-shifting discoveries that revolutionized our understanding of cellular genome maintenance, he was awarded the Nobel Prize in Chemistry in 2015 jointly with Tomas Lindahl and Aziz Sancar.
Beyond his experimental breakthroughs, Modrich has profoundly shaped cancer research by elucidating the molecular basis for hereditary cancer syndromes and establishing critical links between DNA repair deficiencies and disease pathogenesis. His rigorous biochemical methodologies have set enduring standards for molecular studies of DNA repair mechanisms and continue to guide researchers worldwide in understanding genome stability. As a dedicated mentor, he has trained generations of scientists who now lead laboratories investigating DNA repair and cancer biology across prestigious institutions. Modrich's ongoing research continues to explore the intricate molecular details of mismatch repair and its broader implications for human health, including connections to neurodegenerative conditions, cementing his legacy as a meticulous experimentalist whose work continues to transform biomedical science.
