Associate Professor of Molecular Genetics and Microbiology
Research in the Sullivan Lab is focused on chromosome organization, with a specific emphasis on the genomics and epigenetics of the chromosomal locus called the centromere and the formation and fate of chromosome abnormalities that are associated with birth defects, reproductive abnormalities, and cancer. The centromere is a specialized chromosomal site involved in chromosome architecture and movement, kinetochore function, heterochromatin assembly, and sister chromatid cohesion. Our experiments have uncovered a unique type of chromatin (CEN chromatin) formed exclusively at the centromere by replacement of core histone H3 by the centromeric histone variant CENP-A. We are currently exploring the composition of CEN chromatin and its relationship to the underlying alpha satellite DNA at the centromere. Recently, we discovered that the amount and type of genomic variation within alpha satellite DNA affects centromere location and chromosome stability. Variation within the repetitive portion of the human genome has not been well studied, primarily because alpha satellite DNA is part of the 10% of the human genome that has been excluded from the contiguous genome assembly. We are currently using endogenous chromosomes and human artificial chromosomes (HACs) to investigate how alpha satellite variation affects centromeric transcription, recruitment of centromere proteins, <em>de novo</em> centromere assembly, kinetochore architecture, and ultimately, chromosome stability. Finally, the lab studies human chromosomal abnormalities with two centromeres, called dicentric chromosomes. Originally described by Barbara McClintock in the 1930s, dicentrics have been considered inherently unstable chromosomes that trigger genome instability. However, dicentric chromosomes in humans are very stable and often transmitted through the germ line. Using several approaches to experimentally reproduce dicentric chromosome rearrangements in human cells, we are exploring dicentric formation and fate, using genome engineering (CRISPR), live cell imaging, and quantitative microscopy.