BS - Rochester Institute of Technology
PhD - Boston University / National Institutes of Health (Graduate Partnerships Program)
Postdoctoral Training - Whitehead Institute for Biomedical Research
To produce the right complements of proteins that enable cell type-specific behaviors, cells interpret the instructions in DNA through gene "transcription" or "expression." Proper gene expression depends on complex rules and physical interactions between a multitude of components. Improper transcription of genes or proper transcription of broken genes is central to many human diseases.
The Abraham lab studies how gene transcription is controlled, including how the genome is organized in the nucleus and how specific genes are regulated by environmental cues. We also study how transcriptional processes are altered in disease to either understand the disease or to suggest treatments. We develop and deploy computational pipelines to synthesize and distill complicated transcriptional processes and how they go awry in diseased cells. Much of our work centers on the study of super-enhancers [https://en.wikipedia.org/wiki/Super-enhancer], arrangements of transcription-regulating DNA elements that allow genes especially important for a cell's identity to be tightly controlled by the cell's environment. These super-enhancers have proven useful for identifying regulators of cell identity , regulation of genes by signaling pathways , genes required for tumor cell survival [3, 4], targetable protein nodes in cancers , and important mutations in tumor genomes [6, 7]. Super-enhancers and their associated genes can be aggregated to computationally model the core regulatory circuitry dictating the identities of specific cell types.
Super-enhancers are also physical entities in cell nuclei that are important contributors to structuring the genome within the nucleus. Our goals are to identify loci in the nucleus where transcriptional enhancers interact to form super-enhancers using genome structure data, and to uncover genes regulated by these structures in healthy and diseased cells. We are developing algorithms that leverage high-throughput sequencing data to identify these collections, the genes that they control, and the processes that mediate their functions.
Durbin AD, Zimmerman MW, Dharia NV, Abraham BJ, Iniguez AB, Weichert-Leahey N, He S, Krill-Burger JM, Root DE, Vazquez F, Tsherniak A, Hahn WC, Golub TR, Young RA, Look AT, Stegmaier K. Selective gene dependencies in MYCN-amplified neuroblastoma include the core transcriptional regulatory circuitry. Nat Genet Sep;50(9):1240-1246, 2018. doi: 10.1038/s41588-018-0191-z. Epub 2018 Aug 20.
Abraham BJ, Hnisz D, Weintraub AS, Kwiatkowski N, Li CH, Li Z, Weichert-Leahey N, Rahman S, Liu Y, Etchin J, Li B, Shen S, Lee TI, Zhang J, Look AT, Mansour MR, Young RA. Small genomic insertions form enhancers that misregulate oncogenes. Nat Commun Feb 9;8:14385, 2017. doi: 10.1038/ncomms14385.
Hnisz D, Schuijers J, Lin CY, Weintraub AS, Abraham BJ, Lee TI, Bradner JE, Young RA. Convergence of developmental and oncogenic signaling pathways at transcriptional super-enhancers. Mol Cell Apr 16;58(2):362-70, 2015. doi: 10.1016/j.molcel.2015.02.014. Epub 2015 Mar 19.
Kwiatkowski N, Zhang T, Rahl PB, Abraham BJ, Reddy J, Ficarro SB, Dastur A, Amzallag A, Ramaswamy S, Tesar B, Jenkins CE, Hannett NM, McMillin D, Sanda T, Sim T, Kim ND, Look T, Mitsiades CS, Weng AP, Brown JR, Benes CH, Marto JA, Young RA, Gray NS. Targeting transcription regulation in cancer with a covalent CDK7 inhibitor. Nature Jul 31;511(7511):616-20, 2014. doi: 10.1038/nature13393. Epub 2014 Jun 22.
Mansour MR, Abraham BJ, Anders L, Berezovskaya A, Gutierrez A, Durbin AD, Etchin J, Lawton L, Sallan SE, Silverman LB, Loh ML, Hunger SP, Sanda T, Young RA, Look AT. An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element. Science Dec 12;346(6215):1373-7, 2014. doi: 10.1126/science.1259037. Epub 2014 Nov 13.
Whyte WA, Orlando DA, Hnisz D, Abraham BJ, Lin CY, Kagey MH, Rahl PB, Lee TI, Young RA. Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell Apr 11;153(2):307-19, 2013. doi: 10.1016/j.cell.2013.03.035.
Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-André V, Sigova AA, Hoke HA, Young RA. Super-enhancers in the control of cell identity and disease. Cell Nov 7;155(4):934-47, 2013. doi: 10.1016/j.cell.2013.09.053. Epub 2013 Oct 10.
Last update: April 2019