Brian J. Abraham, PhD
Brian J. Abraham, PhD

Brian J. Abraham, PhD

Assistant Member, St. Jude Faculty

  • Course Director, Computational Biology, St. Jude Graduate School of Biomedical Sciences

Departments

Education

BS - Rochester Institute of Technology
PhD - Boston University / National Institutes of Health (Graduate Partnerships Program)
Postdoctoral Training - Whitehead Institute for Biomedical Research

Research Interests

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, 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, targetable protein nodes in cancers, and important mutations in tumor genomes.  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.    

Abraham Lab

Contact Information

Brian J. Abraham, PhD Computational Biology MS 1135, Room IA6050 St. Jude Children's Research Hospital 262 Danny Thomas Place Memphis, TN 38105-3678

St. Jude Faculty List

Related Topics

News Releases

Selected Publications

Prutsch N, He S, Berezovskaya A, Durbin AD, Dharia NV, Maher KA, Matthews JD, Hare L, Turner SD, Stegmaier K, Kenner L, Merkel O, Look AT, Abraham BJ, Zimmerman MW. STAT3 couples activated tyrosine kinase signaling to the oncogenic core transcriptional regulatory circuitry of anaplastic large cell lymphoma. Cell Rep Med Mar 19;5(3):101472, 2024. doi: 10.1016/j.xcrm.2024.101472. PMID: 38508140; PMCID: PMC10983107.

Durbin AD, Wang T, Wimalasena VK, Zimmerman MW, Li D, Dharia NV, Mariani L, Shendy NAM, Nance S, Patel AG, Shao Y, Mundada M, Maxham L, Park PMC, Sigua LH, Morita K, Conway AS, Robichaud AL, Perez-Atayde AR, Bikowitz MJ, Quinn TR, Wiest O, Easton J, Schönbrunn E, Bulyk ML, Abraham BJ, Stegmaier K, Look AT, Qi J. EP300 Selectively Controls the Enhancer Landscape of MYCN-Amplified Neuroblastoma. Cancer Discov Mar 1;12(3):730-751, 2022 . doi: 10.1158/2159-8290.CD-21-0385. PMID: 34772733; PMCID: PMC8904277.

Adetunji MO, Abraham BJ. SEAseq: a portable and cloud-based chromatin occupancy analysis suite. BMC Bioinformatics Feb 23;23(1):77, 2022. doi: 10.1186/s12859-022-04588-z. PMID: 35193506; PMCID: PMC8864840.

Reddy J, Fonseca MAS, Corona RI, Nameki R, Segato Dezem F, Klein IA, Chang H, Chaves-Moreira D, Afeyan LK, Malta TM, Lin X, Abbasi F, Font-Tello A, Sabedot T, Cejas P, Rodríguez-Malavé N, Seo JH, Lin DC, Matulonis U, Karlan BY, Gayther SA, Pasaniuc B, Gusev A, Noushmehr H, Long H, Freedman ML, Drapkin R, Young RA, Abraham BJ, Lawrenson K. Predicting master transcription factors from pan-cancer expression data. Sci Adv Nov 26;7(48):eabf6123, 2021. doi: 10.1126/sciadv.abf6123. Epub Nov 24, 2021. PMID: 34818047; PMCID: PMC8612691.

Zimmerman MW, Durbin AD, He S, Oppel F, Shi H, Tao T, Li Z, Berezovskaya A, Liu Y, Zhang J, Young RA, Abraham BJ, Look AT. Retinoic acid rewires the adrenergic core regulatory circuitry of childhood neuroblastoma. Sci Adv Oct 22;7(43):eabe0834, 2021. doi: 10.1126/sciadv.abe0834. Epub Oct 20, 2021. PMID: 34669465; PMCID: PMC8528416.

Choudhuri A, Trompouki E, Abraham BJ, Colli LM, Kock KH, Mallard W, Yang ML, Vinjamur DS, Ghamari A, Sporrij A, Hoi K, Hummel B, Boatman S, Chan V, Tseng S, Nandakumar SK, Yang S, Lichtig A, Superdock M, Grimes SN, Bowman TV, Zhou Y, Takahashi S, Joehanes R, Cantor AB, Bauer DE, Ganesh SK, Rinn J, Albert PS, Bulyk ML, Chanock SJ, Young RA, Zon LI. Common variants in signaling transcription-factor-binding sites drive phenotypic variability in red blood cell traits. Nat Genet Dec;52(12):1333-1345, 2020. doi: 10.1038/s41588-020-00738-2. Epub Nov 23, 2020. PMID: 33230299; PMCID: PMC7876911.

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 Aug 20, 2018.

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 Mar 19, 2015.

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 Jun 22, 2014.

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 Nov 13, 2014..

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 Oct 10, 2013.

Last update: April 2024

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