Laird, Charles

Dr. Laird's research focuses on fragile X syndrome, a complex genetic disease whose primary phenotype is intellectual and other developmental disabilities. This syndrome encompasses the new paradigms of triplet repeat diseases and imprinting disorders: it exhibits both an expansion of a CGG trinucleotide repeat, and the inactivation of a critical gene, FMR1, by hypermethylation. A long-term objective of Laird's research is to understand these two aspects of the etiology of fragile-X syndrome, their possible interrelationship, and their relevance to other epigenetic and triplet-repeat diseases. In addition, his lab's characterizations of methylation of FMR1 and of the relationship between DNA replication and the cell cycle are providing new insights into two normal processes: the nature of DNA replication very late in the cell cycle, and the fidelity of inheritance of methylation through somatic cell division. Laird’s most recent work on epigenetics is facilitated by development of three new methods that permit recognition of methylation patterns on both strands of individual DNA molecules. "Hairpin-bisulfite PCR" allows inference of regional rates of maintenance and de novo methylation for the FMR1 locus in leukocytes that were not subjected to cell culture or other manipulation. A "population-epigenetic" model of DNA methylation allows calculation of CpG site-specific methylation rates using new double-strand methylation data. Another method contributes to the authenticity of methylation data, and allows high confidence in the results.