Now showing items 1-20 of 29

    • Biased Multicomponent Reactions to Develop Novel Bromodomain Inhibitors 

      McKeown, Michael R; Shaw, Daniel L; Fu, Harry; Liu, Shuai; Xu, Xiang; Marineau, Jason J; Huang, Yibo; Zhang, Xiaofeng; Buckley, Dennis L; Kadam, Asha; Zhang, Zijuan; Blacklow, Stephen C; Qi, Jun; Zhang, Wei; Bradner, James E (American Chemical Society, 2014)
      BET bromodomain inhibition has contributed new insights into gene regulation and emerged as a promising therapeutic strategy in cancer. Structural analogy of early methyl-triazolo BET inhibitors has prompted a need for ...
    • Chemical genetic strategy identifies histone deacetylase 1 (HDAC1) and HDAC2 as therapeutic targets in sickle cell disease 

      Bradner, James Elliott; Mak, Raymond Heungwing; Tanguturi, Shyam Kumar; Mazitschek, Ralph; Haggarty, Stephen John; Ross, Kenneth N; Chang, Cindy Y.; Bosco, Jocelyn; West, Nathan; Morse, Elizabeth; Lin, Katherine; Shen, John Paul; Kwiatkowski, Nicholas Paul; Gheldof, Nele; Dekker, Job; DeAngelo, Daniel J.; Carr, Steven A.; Schreiber, Stuart L.; Golub, Todd Robert; Ebert, Benjamin L. (Proceedings of the National Academy of Sciences, 2010)
      The worldwide burden of sickle cell disease is enormous, with over 200,000 infants born with the disease each year in Africa alone. Induction of fetal hemoglobin is a validated strategy to improve symptoms and complications ...
    • Chemical Probes and the Exploration of Bromodomains in Cancer Biology 

      McKeown, Michael Robert (2014-06-06)
      The post-translational modification of histones and their interaction with transcription factors is essential to gene regulation. Furthermore, these targets would greatly benefit from probe molecules to fully elucidate ...
    • Clinicopathologic Features and Long-term Outcomes of NUT Midline Carcinoma 

      Bauer, Daniel Evan; Mitchell, C. M.; Strait, K. M.; Lathan, Christopher Scott; Stelow, E. B.; Luer, S. C.; Muhammed, S.; Evans, A. G.; Sholl, Lynette Marie; Rosai, J.; Giraldi, E.; Oakley, R. P.; Rodriguez-Galindo, C; London, Wendy B; Sallan, Stephen Earl; Bradner, James Elliott; French, Christopher Alexander (American Association for Cancer Research (AACR), 2012)
      Purpose NUT midline carcinoma (NMC) is a poorly differentiated squamous cancer characterized by rearrangement of the NUT gene. Research advances have provided opportunities for targeted therapy in NMC, yet the clinical ...
    • The Development of Chemical and Computational Tools to Study Transcriptional Regulation in Cancer 

      Federation, Alexander Joel (2015-05-01)
      Eukaryotic gene regulation is a complex process requiring the action of many multicomponent complexes in the cell. Specific inhibitors of chromatin-associated factors allow the functional study of protein domains without ...
    • Dose-dependent role of the cohesin complex in normal and malignant hematopoiesis 

      Viny, Aaron D.; Ott, Christopher J.; Spitzer, Barbara; Rivas, Martin; Meydan, Cem; Papalexi, Efthymia; Yelin, Dana; Shank, Kaitlyn; Reyes, Jaime; Chiu, April; Romin, Yevgeniy; Boyko, Vitaly; Thota, Swapna; Maciejewski, Jaroslaw P.; Melnick, Ari; Bradner, James E.; Levine, Ross L. (The Rockefeller University Press, 2015)
      Cohesin complex members have recently been identified as putative tumor suppressors in hematologic and epithelial malignancies. The cohesin complex guides chromosome segregation; however, cohesin mutant leukemias do not ...
    • Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition 

      Tang, Yujie; Gholamin, Sharareh; Schubert, Simone; Willardson, Minde I.; Lee, Alex; Bandopadhayay, Pratiti; Bergthold, Guillame; Masoud, Sabran; Nguyen, Brian; Vue, Nujsaubnusi; Balansay, Brianna; Yu, Furong; Oh, Sekyung; Woo, Pamelyn; Chen, Spenser; Ponnuswami, Anitha; Monje, Michelle; Atwood, Scott X.; Whitson, Ramon J.; Mitra, Siddhartha; Cheshier, Samuel H.; Qi, Jun; Beroukhim, Rameen; Tang, Jean Y.; Wechsler-Reya, Rob; Oro, Anthony E.; Link, Brian A.; Bradner, James E.; Cho, Yoon-Jae (2014)
      Hedgehog signaling drives oncogenesis in several cancers and strategies targeting this pathway have been developed, most notably through inhibition of Smoothened. However, resistance to Smoothened inhibitors occurs via ...
    • An epigenomic approach to therapy for tamoxifen-resistant breast cancer 

      Feng, Qin; Zhang, Zheng; Shea, Martin J; Creighton, Chad J; Coarfa, Cristian; Hilsenbeck, Susan G; Lanz, Rainer; He, Bin; Wang, Lei; Fu, Xiaoyong; Nardone, Agostina; Song, Yongcheng; Bradner, James; Mitsiades, Nicholas; Mitsiades, Constantine S; Osborne, C Kent; Schiff, Rachel; O'Malley, Bert W (Nature Publishing Group, 2014)
      Tamoxifen has been a frontline treatment for estrogen receptor alpha (ERα)-positive breast tumors in premenopausal women. However, resistance to tamoxifen occurs in many patients. ER still plays a critical role in the ...
    • From transcriptional regulation to drugging the cancer epigenome 

      Bradner, James E (BioMed Central, 2014)
      Jay Bradner discusses the opportunities and challenges for the study and therapeutic targeting of the cancer epigenome, as well as innovative approaches to drug discovery.
    • Genetic resistance to JAK2 enzymatic inhibitors is overcome by HSP90 inhibition 

      Weigert, Oliver; Bird, Liat; Kopp, Nadja; van Bodegom, Diederik; Marubayashi, Sachie; Christie, Amanda L.; Paranal, Ronald M.; Gaul, Christoph; Vangrevelinghe, Eric; Romanet, Vincent; Murakami, Masato; Tiedt, Ralph; Ebel, Nicolas; Evrot, Emeline; De Pover, Alain; Régnier, Catherine H.; Erdmann, Dirk; Hofmann, Francesco; Levine, Ross L.; Baffert, Fabienne; Radimerski, Thomas; Lane, Andrew Alan; Chapuy, Bjoern; Toms, Angela Vivian; McKeown, Michael Robert; Bradner, James Elliott; Yoda, Akinori; Eck, Michael Joseph; Sallan, Stephen Earl; Kung, Andrew; Weinstock, David Marc (The Rockefeller University Press, 2012)
      Enzymatic inhibitors of Janus kinase 2 (JAK2) are in clinical development for the treatment of myeloproliferative neoplasms (MPNs), B cell acute lymphoblastic leukemia (B-ALL) with rearrangements of the cytokine receptor ...
    • Genome-wide determination of drug localization 

      Anders, Lars; Guenther, Matthew G.; Qi, Jun; Fan, Zi Peng; Marineau, Jason J.; Rahl, Peter B.; Lovén, Jakob; Sigova, Alla A.; Smith, William B.; Lee, Tong Ihn; Bradner, James E.; Young, Richard A. (2014)
      A vast number of small-molecule ligands, including therapeutic drugs under development and in clinical use, elicit their effects by binding specific proteins associated with the genome. An ability to map the direct ...
    • HDAC2 Negatively Regulates Memory Formation and Synaptic Plasticity 

      Guan, Ji-Song; Giacometti, Emanuela; Dannenberg, Jan-Hermen; Joseph, Nadine; Gao, Jun; DePinho, Ronald A.; Jaenisch, Rudolf; Tsai, Li-Huei; Haggarty, Stephen John; Nieland, Thomas; Zhou, Ying; Wang, Xinyu; Mazitschek, Ralph; Bradner, James Elliott (Nature Publishing Group, 2012)
      Chromatin modifications, especially histone-tail acetylation, have been implicated in memory formation. Increased histone-tail acetylation induced by inhibitors of histone deacetylases (HDACis) facilitates learning and ...
    • Identification and Characterization of Small Molecule Inhibitors of a Class I Histone Deacetylase from Plasmodium falciparum 

      Nguyen, Cokey; Urgaonkar, Sameer; Cortese, Joseph; Barker, Robert H.; Greenberg, Edward; Tang, Weiping; Patel, Vishal; Mazitschek, Ralph; Coleman, Bradley Ian; Bradner, James Elliott; Schreiber, Stuart L.; Duraisingh, Manoj T.; Wirth, Dyann Fergus; Clardy, Jon C. (American Chemical Society, 2009)
      A library of approximately 2000 small molecules biased toward inhibition of histone deacetylases was assayed for antimalarial activity in a high-throughput P. falciparum viability assay. Active compounds were cross-analyzed ...
    • Lessons From Cyclosporine A: Structural Determinants of Conformation-Switching and Passive Membrane Penetration 

      May, Erin Mallory (2015-10-15)
      The structural complexity of ‘beyond-rule-of-5’ compounds, such as peptide macrocycles, may facilitate access to additional biological target space beyond the enzymatic active site. Naturally occurring cyclic peptides, in ...
    • MYB-QKI rearrangements in Angiocentric Glioma drive tumorigenicity through a tripartite mechanism 

      Bandopadhayay, Pratiti; Ramkissoon, Lori A.; Jain, Payal; Bergthold, Guillaume; Wala, Jeremiah; Zeid, Rhamy; Schumacher, Steven E.; Urbanski, Laura; O’Rourke, Ryan; Gibson, William J.; Pelton, Kristine; Ramkissoon, Shakti H.; Han, Harry J.; Zhu, Yuankun; Choudhari, Namrata; Silva, Amanda; Boucher, Katie; Henn, Rosemary E.; Kang, Yun Jee; Knoff, David; Paolella, Brenton R.; Gladden-Young, Adrianne; Varlet, Pascale; Pages, Melanie; Horowitz, Peleg M.; Federation, Alexander; Malkin, Hayley; Tracy, Adam; Seepo, Sara; Ducar, Matthew; Hummelen, Paul Van; Santi, Mariarita; Buccoliero, Anna Maria; Scagnet, Mirko; Bowers, Daniel C.; Giannini, Caterina; Puget, Stephanie; Hawkins, Cynthia; Tabori, Uri; Klekner, Almos; Bognar, Laszlo; Burger, Peter C.; Eberhart, Charles; Rodriguez, Fausto J.; Hill, D. Ashley; Mueller, Sabine; Haas-Kogan, Daphne A.; Phillips, Joanna J.; Santagata, Sandro; Stiles, Charles D.; Bradner, James E.; Jabado, Nada; Goren, Alon; Grill, Jacques; Ligon, Azra H.; Goumnerova, Liliana; Waanders, Angela J.; Storm, Phillip B.; Kieran, Mark W.; Ligon, Keith L.; Beroukhim, Rameen; Resnick, Adam C. (2016)
      Angiocentric gliomas are pediatric low-grade gliomas (PLGGs) without known recurrent genetic drivers. We performed genomic analysis of new and published data from 249 PLGGs including 19 Angiocentric Gliomas. We identified ...
    • Notch Inhibition Allows Oncogene-Independent Generation of iPS Cells 

      Ichida, Justin K.; TCW, Julia; Williams Gonzalez, Luis Alberto; Carter, Ava; Shi, Yingxiao; Moura, Marcelo T.; Ziller, Michael Johannes; Singh, Sean; Amabile, Giovanni; Bock, Christoph; Umezawa, Akihiro; Rubin, Lee; Bradner, James Elliott; Akutsu, Hidenori; Meissner, Alexander; Eggan, Kevin Carl (Nature Publishing Group, 2014)
      The reprogramming of somatic cells to pluripotency using defined transcription factors holds great promise for biomedicine. However, human reprogramming remains inefficient and relies either on the use of the potentially ...
    • An oncogenic Ezh2 mutation cooperates with particular genetic alterations to induce tumors in mice and redistributes H3K27 trimethylation throughout the genome 

      Souroullas, George P.; Jeck, William R.; Parker, Joel S.; Simon, Jeremy M.; Liu, Jie-Yu; Paulk, Joshiawa; Xiong, Jessie; Clark, Kelly S.; Fedoriw, Yuri; Qi, Jun; Burd, Christin E.; Bradner, James E.; Sharpless, Norman E. (2016)
      B-cell lymphoma and melanoma harbor recurrent mutations in the gene encoding the EZH2 histone methyltransferase, but the carcinogenic role of these mutations is unclear. Here we describe a mouse model in which the most ...
    • An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma 

      Drier, Yotam; Cotton, Matthew J.; Williamson, Kaylyn E.; Gillespie, Shawn M.; Ryan, Russell J.H.; Kluk, Michael J.; Carey, Christopher D.; Rodig, Scott J.; Sholl, Lynette M; Afrogheh, Amir H.; Faquin, William C.; Queimado, Lurdes; Qi, Jun; Wick, Michael J.; El-Naggar, Adel K.; Bradner, James E.; Moskaluk, Christopher A.; Aster, Jon C.; Knoechel, Birgit; Bernstein, Bradley E. (2016)
      Translocation events are frequent in cancer and may create chimeric fusions or ‘regulatory rearrangements’ that drive oncogene overexpression. Here we identify super-enhancer translocations that drive overexpression of the ...
    • Regulation of MYC Expression and Differential JQ1 Sensitivity in Cancer Cells 

      Fowler, Trent; Ghatak, Payel; Price, David H.; Conaway, Ronald; Conaway, Joan; Chiang, Cheng-Ming; Bradner, James E.; Shilatifard, Ali; Roy, Ananda L. (Public Library of Science, 2014)
      High level MYC expression is associated with almost all human cancers. JQ1, a chemical compound that inhibits MYC expression is therapeutically effective in preclinical animal models in midline carcinoma, and Burkitt’s ...
    • Repression of BIM mediates survival signaling by MYC and AKT in high-risk T-cell acute lymphoblastic leukemia 

      Reynolds, Christine; Roderick, Justine E.; LaBelle, James L.; Bird, Gregory; Mathieu, Ronald; Bodaar, Kimberly; Colon, Diana; Pyati, Ujwal; Stevenson, Kristen E.; Qi, Jun; Harris, Marian; Silverman, Lewis B.; Sallan, Stephen E.; Bradner, James E.; Neuberg, Donna S.; Look, A. Thomas; Walensky, Loren D.; Kelliher, Michelle A.; Gutierrez, Alejandro (2014)
      Treatment resistance in T-cell acute lymphoblastic leukemia (T-ALL) is associated with PTEN deletions and resultant PI3K-AKT pathway activation, as well as MYC overexpression, and these pathways repress mitochondrial ...