BBS Faculty Member - James Bradner

James Bradner

Department of Medicine, HMS
Division of Hematologic Neoplasia, DFCI

Dana Farber Cancer Institute
Armenise Building, Room 641
210 Longwood Ave.
Boston, MA 02115
Tel: 617-632-6629
Fax: 617-582-7370
Email: james_bradner@dfci.harvard.edu
Visit my lab page here.



The Bradner Laboratory studies gene regulatory pathways using the emerging discipline of chemical biology. We focus on cancer, as cancer is a dreadful disease which remains largely incurable. We choose to study cancer biology with chemistry, because if we are successful in controlling cell identity in this manner, new types of chemical probes and therapeutics will emerge directly from these efforts.

We consider cancer as a disease of cell state, caused by genetic alterations but influenced also by the cell type of origin and the manner in which the genome is packaged. The insight that no known set of genetic alterations are capable of causing cancer in all cell types establishes the plausibility that reprogramming the cell's fundamental identity may subvert the aggressive behavior of cancer.

In addition, recent research has observed high genetic complexity, heterogeneity, plasticity and redundancy of signaling networks in cancer. These findings further establish the pressing need for molecules directed against the master regulatory proteins maintaining cancer cell identity.

We have initiated research aimed at three sets of targets:

1. Transcription Factors

2. Chromatin modifying enzymes

3. Histone binding modules

In the post-genomic era, the discovery of cancer genes has become relatively straightforward. Cancer biologists and geneticists now race, like modern cartographers, to assimilate this information as a unified geography of cell signaling pathways. For the cancer patient, these advances allow a detailed, highly individualized understanding of cancer's hard-wiring. Unfortunately, the delay in the discovery and delivery of targeted therapeutics remains a significant concern. We invoke a utilitarian model of drug discovery which is not restricted by any individual chemistry or technology. We support a collaborative, creative approach to drug discovery focused on the most pressing targets irrespective of perceived 'druggability' or profitability. We perform this research at the Dana-Farber Cancer Institute and the Harvard Medical School, in close collaborative proximity of scientists, clinicians and patients.



Last Update: 8/9/2013



Publications

For a complete listing of publications click here.

 


 

Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, Morse EM, Keates T, Hickman TT, Felletar I, Philpott M, Munro S, West N, Cameron MJ, Heightman TD, La Thangue N, Kung A, French CA, Wiest O, Knapp S, Bradner JE. Selective inhibition of BET bromodomains. Nature. 2010 Dec 23;468(7327):1067-73. Epub 2010 Sep 24.

Moellering RE, Cornejo M, Davis TN, Del Bianco C, Aster JC, Blacklow SC, Kung AL, Gilliland DG, Verdine GL, Bradner JE. Direct inhibition of the NOTCH transcription factor complex. Nature. 2009 Nov 12;462(7270):182-8.

Bowers A, Greshock TJ, West N, Estiu G, Schreiber SL, Wiest O, Williams, RM and Bradner JE. Synthesis and Conformation-Activity Relationships of the Peptide Isosteres of FK228 and Largazole. J Am Chem Soc. 2009 Feb 4.

Bradner JE*, West N, Grachan ML, Greenberg EF, Haggarty SJ, Warnow T, Mazitschek R*. Chemical phylogenetics of histone deacetylases. (*Co-corresponding authors).
Nat Chem Biol. 2010 Mar;6(3):238-243. Epub 2010 Feb 7.



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