Search Results - "Bradner, James E."

Selective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers by Lovén, Jakob, Hoke, Heather A., Lin, Charles Y., Lau, Ashley, Orlando, David A., Vakoc, Christopher R., Bradner, James E., Lee, Tong Ihn, Young, Richard A.

“…Chromatin regulators have become attractive targets for cancer therapy, but it is unclear why inhibition of these ubiquitous regulators should have…”
Get full text

Transcriptional Amplification in Tumor Cells with Elevated c-Myc by Lin, Charles Y., Lovén, Jakob, Rahl, Peter B., Paranal, Ronald M., Burge, Christopher B., Bradner, James E., Lee, Tong Ihn, Young, Richard A.

“…Elevated expression of the c-Myc transcription factor occurs frequently in human cancers and is associated with tumor aggression and poor clinical outcome. The…”
Get full text

Convergence of Developmental and Oncogenic Signaling Pathways at Transcriptional Super-Enhancers by Hnisz, Denes, Schuijers, Jurian, Lin, Charles Y., Weintraub, Abraham S., Abraham, Brian J., Lee, Tong Ihn, Bradner, James E., Young, Richard A.

“…Super-enhancers and stretch enhancers (SEs) drive expression of genes that play prominent roles in normal and disease cells, but the functional importance of…”
Get full text

RNA Exosome-Regulated Long Non-Coding RNA Transcription Controls Super-Enhancer Activity by Pefanis, Evangelos, Wang, Jiguang, Rothschild, Gerson, Lim, Junghyun, Kazadi, David, Sun, Jianbo, Federation, Alexander, Chao, Jaime, Elliott, Oliver, Liu, Zhi-Ping, Economides, Aris N., Bradner, James E., Rabadan, Raul, Basu, Uttiya

“…We have ablated the cellular RNA degradation machinery in differentiated B cells and pluripotent embryonic stem cells (ESCs) by conditional mutagenesis of core…”
Get full text

Phthalimide conjugation as a strategy for in vivo target protein degradation by Winter, Georg E., Buckley, Dennis L., Paulk, Joshiawa, Roberts, Justin M., Souza, Amanda, Dhe-Paganon, Sirano, Bradner, James E.

“…The development of effective pharmacological inhibitors of multidomain scaffold proteins, notably transcription factors, is a particularly challenging problem…”
Get full text

Functional Genomic Landscape of Human Breast Cancer Drivers, Vulnerabilities, and Resistance by Marcotte, Richard, Sayad, Azin, Brown, Kevin R., Sanchez-Garcia, Felix, Reimand, Jüri, Haider, Maliha, Virtanen, Carl, Bradner, James E., Bader, Gary D., Mills, Gordon B., Pe’er, Dana, Moffat, Jason, Neel, Benjamin G.

“…Large-scale genomic studies have identified multiple somatic aberrations in breast cancer, including copy number alterations and point mutations. Still,…”
Get full text

Sensitivity of human lung adenocarcinoma cell lines to targeted inhibition of BET epigenetic signaling proteins by Lockwood, William W., Zejnullahu, Kreshnik, Bradner, James E., Varmus, Harold

“…Bromodomain and extra terminal domain (BET) proteins function as epigenetic signaling factors that associate with acetylated histones and facilitate…”
Get full text

BET Bromodomain Inhibition Promotes Anti-tumor Immunity by Suppressing PD-L1 Expression by Zhu, Hengrui, Bengsch, Fee, Svoronos, Nikolaos, Rutkowski, Melanie R., Bitler, Benjamin G., Allegrezza, Michael J., Yokoyama, Yuhki, Kossenkov, Andrew V., Bradner, James E., Conejo-Garcia, Jose R., Zhang, Rugang

“…Restoration of anti-tumor immunity by blocking PD-L1 signaling through the use of antibodies has proven to be beneficial in cancer therapy. Here, we show…”
Get full text

Discovery and Characterization of Super-Enhancer-Associated Dependencies in Diffuse Large B Cell Lymphoma by Chapuy, Bjoern, McKeown, Michael R., Lin, Charles Y., Monti, Stefano, Roemer, Margaretha G.M., Qi, Jun, Rahl, Peter B., Sun, Heather H., Yeda, Kelly T., Doench, John G., Reichert, Elaine, Kung, Andrew L., Rodig, Scott J., Young, Richard A., Shipp, Margaret A., Bradner, James E.

“…Diffuse large B cell lymphoma (DLBCL) is a biologically heterogeneous and clinically aggressive disease. Here, we explore the role of bromodomain and…”
Get full text

The Myeloma Drug Lenalidomide Promotes the Cereblon-Dependent Destruction of Ikaros Proteins by Lu, Gang, Middleton, Richard E., Sun, Huahang, Naniong, MarkVic, Ott, Christopher J., Mitsiades, Constantine S., Wong, Kwok-Kin, Bradner, James E., Kaelin, William G.

“…Thalidomide-like drugs such as lenalidomide are clinically important treatments for multiple myeloma and show promise for other B cell malignancies. The…”
Get full text

Plasticity in binding confers selectivity in ligand-induced protein degradation by Nowak, Radosław P., DeAngelo, Stephen L., Buckley, Dennis, He, Zhixiang, Donovan, Katherine A., An, Jian, Safaee, Nozhat, Jedrychowski, Mark P., Ponthier, Charles M., Ishoey, Mette, Zhang, Tinghu, Mancias, Joseph D., Gray, Nathanael S., Bradner, James E., Fischer, Eric S.

“…Heterobifunctional small-molecule degraders that induce protein degradation through ligase-mediated ubiquitination have shown considerable promise as a new…”
Get full text

YY1 Is a Structural Regulator of Enhancer-Promoter Loops by Weintraub, Abraham S., Li, Charles H., Zamudio, Alicia V., Sigova, Alla A., Hannett, Nancy M., Day, Daniel S., Abraham, Brian J., Cohen, Malkiel A., Nabet, Behnam, Buckley, Dennis L., Guo, Yang Eric, Hnisz, Denes, Jaenisch, Rudolf, Bradner, James E., Gray, Nathanael S., Young, Richard A.

“…There is considerable evidence that chromosome structure plays important roles in gene control, but we have limited understanding of the proteins that…”
Get full text

BET Bromodomains Mediate Transcriptional Pause Release in Heart Failure by Anand, Priti, Brown, Jonathan D., Lin, Charles Y., Qi, Jun, Zhang, Rongli, Artero, Pedro Calderon, Alaiti, M. Amer, Bullard, Jace, Alazem, Kareem, Margulies, Kenneth B., Cappola, Thomas P., Lemieux, Madeleine, Plutzky, Jorge, Bradner, James E., Haldar, Saptarsi M.

“…Heart failure (HF) is driven by the interplay between regulatory transcription factors and dynamic alterations in chromatin structure. Pathologic gene…”
Get full text

NF-κB Directs Dynamic Super Enhancer Formation in Inflammation and Atherogenesis by Brown, Jonathan D., Lin, Charles Y., Duan, Qiong, Griffin, Gabriel, Federation, Alexander J., Paranal, Ronald M., Bair, Steven, Newton, Gail, Lichtman, Andrew H., Kung, Andrew L., Yang, Tianlun, Wang, Hong, Luscinskas, Francis W., Croce, Kevin J., Bradner, James E., Plutzky, Jorge

“…Proinflammatory stimuli elicit rapid transcriptional responses via transduced signals to master regulatory transcription factors. To explore the role of…”
Get full text

A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia by Gröschel, Stefan, Sanders, Mathijs A, Hoogenboezem, Remco, de Wit, Elzo, Bouwman, Britta A M, Erpelinck, Claudia, van der Velden, Vincent H J, Havermans, Marije, Avellino, Roberto, van Lom, Kirsten, Rombouts, Elwin J, van Duin, Mark, Döhner, Konstanze, Beverloo, H Berna, Bradner, James E, Döhner, Hartmut, Löwenberg, Bob, Valk, Peter J M, Bindels, Eric M J, de Laat, Wouter, Delwel, Ruud

“…Chromosomal rearrangements without gene fusions have been implicated in leukemogenesis by causing deregulation of proto-oncogenes via relocation of cryptic…”
Get full text

Quantitative ChIP-Seq Normalization Reveals Global Modulation of the Epigenome by Orlando, David A., Chen, Mei Wei, Brown, Victoria E., Solanki, Snehakumari, Choi, Yoon J., Olson, Eric R., Fritz, Christian C., Bradner, James E., Guenther, Matthew G.

“…Epigenomic profiling by chromatin immunoprecipitation coupled with massively parallel DNA sequencing (ChIP-seq) is a prevailing methodology used to investigate…”
Get full text

Degradation of the BAF Complex Factor BRD9 by Heterobifunctional Ligands by Remillard, David, Buckley, Dennis L., Paulk, Joshiawa, Brien, Gerard L., Sonnett, Matthew, Seo, Hyuk‐Soo, Dastjerdi, Shiva, Wühr, Martin, Dhe‐Paganon, Sirano, Armstrong, Scott A., Bradner, James E.

“…The bromodomain‐containing protein BRD9, a subunit of the human BAF (SWI/SNF) nucleosome remodeling complex, has emerged as an attractive therapeutic target in…”
Get full text

Small-Molecule Inhibition of BRDT for Male Contraception by Matzuk, Martin M., McKeown, Michael R., Filippakopoulos, Panagis, Li, Qinglei, Ma, Lang, Agno, Julio E., Lemieux, Madeleine E., Picaud, Sarah, Yu, Richard N., Qi, Jun, Knapp, Stefan, Bradner, James E.

“…A pharmacologic approach to male contraception remains a longstanding challenge in medicine. Toward this objective, we explored the spermatogenic effects of a…”
Get full text

Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation by Olson, Calla M, Jiang, Baishan, Erb, Michael A, Liang, Yanke, Doctor, Zainab M, Zhang, Zinan, Zhang, Tinghu, Kwiatkowski, Nicholas, Boukhali, Myriam, Green, Jennifer L, Haas, Wilhelm, Nomanbhoy, Tyzoon, Fischer, Eric S, Young, Richard A, Bradner, James E, Winter, Georg E, Gray, Nathanael S

“…A selective small-molecule degrader of CDK9 was generated by conjugating an imide to SNS-032, a promiscuous ATP-site-directed CDK binder. The pharmacological…”
Get full text

Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules by Nabet, Behnam, Ferguson, Fleur M., Seong, Bo Kyung A., Kuljanin, Miljan, Leggett, Alan L., Mohardt, Mikaela L., Robichaud, Amanda, Conway, Amy S., Buckley, Dennis L., Mancias, Joseph D., Bradner, James E., Stegmaier, Kimberly, Gray, Nathanael S.

“…Chemical biology strategies for directly perturbing protein homeostasis including the degradation tag (dTAG) system provide temporal advantages over genetic…”
Get full text