Beth A. Sullivan, PhD
Associate Professor, Molecular Genetics and Microbiology
Beth Sullivan is an Associate Professor in Molecular Genetics and Microbiology and Co-Director of The Duke University Program in Genetics & Genomics (UPGG). She received her PhD in Human Genetics from the University of Maryland, Baltimore (UMAB). She did postdoctoral fellowships at the MRC Human Genetics Unit (Edinburgh, Scotland) and at the Salk Institute (La Jolla, CA), where she studied human and Drosophila chromosome and centromere biology. Prior to joining the Duke faculty in 2005, she was an Assistant Professor of Genetics and Genomics at Boston University School of Medicine. Her lab's research interests include centromere organization and function, chromatin dynamics, and formation and behavior of human chromosomal abnormalities.
Research in the Sullivan Lab involves studying how chromosomes are organized into inherited chromatin domains and understanding mechanisms of formation and behavior of chromosome abnormalities that are associated with birth defects, infertility, miscarriage, mental retardation, and cancer.
A major focus of the lab's research is the centromere, a specialized chromosomal site involved in chromosome architecture and movement, kinetochore function, heterochromatin assembly, and sister chromatid cohesion. Our experiments 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. Centromeres have historically been considered heterochromatic, however, we found that CEN chromatin contains euchromatic modifications of H3, signifying an open or flexible chromatin conformation. These studies are foundational to our current investigations of genomic and functional elements that define centromere identity.
Specifically, we study endogenous and engineered human chromosomes that contain two similar, adjacent blocks of centromeric satellite DNA arrays. On these chromosomes, called discentrics, usually only one satellite array is assembled into a functional centromere. We are testing how and why two physically linked satellite regions are functionally distinct and how the location of the centromere on this type of chromosome is determined. The lab also studies genome stability, specifically the formation and fate of human chromosomal abnormalities. During meiosis and mitosis, chromosome rearrangements often occur that produce dicentric chromosomes. Barbara McClintock, the famous cytogeneticist and Nobel prizewinner, studied dicentric chromosomes in maize (corn) in the 1930s. She described dicentrics as inherently unstable because the two centromeres often segregated to opposite spindle poles in anaphase, leading to repeated chromosome breakage. We have shown that in humans, however, dicentric chromosomes exhibit unprecedented stability because either both centromeres work together to may make a super-centromere, or one of the centromeres is shut off, so that the chromosome behaves as if it has only a single centromere. We are particularly interested in understanding the mechanism of centromere repression - how and when does it occur? To address these questions, we have developed novel ways to generate human dicentric chromosomes in the laboratory. Our current work includes dissecting the process of centromere inactivation, and testing how sequence variation, chromatin remodeling and chromosome structure impact centromeric identity and fate.
Learn more about Dr. Sullivan's research in GenomeLIFE
Earnshaw WC, Allshire RC, Black BE, Bloom K, Brinkley BR, Brown W, Cheeseman IM, Choo KH, Copenhaver GP, Deluca JG, Desai A, Diekmann S, Erhardt S, Fitzgerald-Hayes M, Foltz D, Fukagawa T, Gassmann R, Gerlich DW, Glover DM, Gorbsky GJ, Harrison SC, Heun P, Hirota T, Jansen LE, Karpen G, Kops GJ, Lampson MA, Lens SM, Losada A, Luger K, Maiato H, Maddox PS, Margolis RL, Masumoto H, McAinsh AD, Mellone BG, Meraldi P, Musacchio A, Oegema K, O'Neill RJ, Salmon ED, Scott KC, Straight AF, Stukenberg PT, Sullivan BA, Sullivan KF, Sunkel CE, Swedlow JR, Walczak CE, Warburton PE, Westermann S, Willard HF, Wordeman L, Yanagida M, Yen TJ, Yoda K, Cleveland DW,
Chromosome Res. 2013 Apr 12;. Abstract
Maloney KA, Sullivan LL, Matheny JE, Strome ED, Merrett SL, Ferris A, Sullivan BA,
Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):13704-9. Abstract
O'Neill RJ, Sullivan BA,
Chromosome Res. 2012 Jul;20(5):461-3. Abstract
Stimpson KM, Matheny JE, Sullivan BA,
Chromosome Res. 2012 Jul;20(5):595-605. Abstract
Stimpson KM, Sullivan BA,
Dev Cell. 2012 Jan 17;22(1):1-2. Abstract