My research interests, broadly defined, are in the field of DNA structure and functioning. I am particularly interested in two problems. The first problem is the mechanisms responsible for the genomic instability of various DNA repeats. Uncontrollable expansions of simple DNA repeats causes almost thirty hereditary disorders in humans, including Fragile X mental retardation, Huntington's disease, myotonic dystrophy, and Friedreich's ataxia. My lab was the first to show that progression of the replication fork through those repeats is compromised due to the unusual structural features of repetitive DNA. This led us to propose the replication model for repeat expansions, stipulating that the replication fork stalling and restart are at heart of repeats' instability. We are in the process of substantiating this hypothesis in yeast and mammalian experimental systems.
