Angela N. Koehler, Ph.D.
Research group web site
Office: Koch Institute, 76-361C
Phone: (617) 324-7631
Koch Institute Administrative Assistant: Paul Thompson
Administrative Assistant Phone: (617) 258-0480
Broad Institute Administrative Assistant: Kristina Wright
Administrative Assistant Phone: (617) 714-7344
Research in our group is focused on building chemical tools and methods for studying temporal aspects of transcriptional regulation in development and cancer. Transcription factors that become overactive in disease are promising yet untested targets for therapeutics. These proteins mediate the excessive transcription of genes whose products are required for tumor growth and metastasis. Unlike enzymes, directly modulating the function of a transcription factor requires specific disruption or recruitment of DNA-protein or protein-protein interactions. The discovery or design of small molecules that specifically disrupt or promote these interactions has thus far proven challenging and the protein class is often perceived to be 'undruggable.' While a handful of successes have been published, the chemical biology community has yet to develop general and systematic strategies for directly modulating the function of transcription factors with drug-like small molecules. Our team is developing a general approach to small-molecule probe discovery for transcription factors by coupling direct binding assays with functional assays involving transcriptional and other phenotypic readouts. We use newly discovered probes to study the precise roles of specific oncogenic transcription factors and to address therapeutic hypotheses in cancer. Selected probes may be developed into imaging agents, diagnostic tools, or therapeutic leads.
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