Beth Sullivan, PhD
Assistant Professor

Research in my laboratory focuses on chromosome organization and segregation and genome stability. Specifically, we study how chromosomes are epigenetically assembled and organized into inherited chromatin domains, and the extent to which key organizational and functional aspects of centromeres are conserved between the fruit fly, Drosophila melanogaster, and humans. We are studying how a unique type of chromatin organization is established at centromeres, how epigenetic signatures produced from distinctive histone modifications contribute to centromere identity, regulation of the dynamic interplay between centromeric chromatin and heterochromatin, and the effect of centromeric chromatin on gene expression. Current projects include studying the mechanisms that regulate the exclusive deposition of the variant histone CENP-A at centromeres and identifying factors that monitor stability and dynamics of centromeric chromatin domains. We have developed assays to functionally test the roles of specific structural elements in chromosome assembly and plan to use genomic and proteomic techniques to integrate chromatin architecture and genomic structure at centromeres.

Chromosome dysfunction is associated with disease states, such as birth defects and cancer, and reproductive phenotypes, such as infertility and miscarriage. Current efforts are aimed at altering chromosomal regions using RNAi and/or genetic and chromosomal mutants to understand the basis of chromosome dysfunction in disease states. In flies, we use a series of deleted minichromosomes to investigate chromatin organization, centromere function, gene expression, and chromosome stability. In humans, we study patient-derived and engineered chromosome rearrangements to determine how underlying chromatin structure predisposes chromosomes to rearrangement and contributes to aneuploidy and chromosome instability. Human chromosomal rearrangements are also being used to understand how the genome is partitioned into functional nuclear compartments.