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职业迁徙
个人简介
The Koehler lab is focused on building chemical tools and methods for studying temporal aspects of transcriptional regulation in development and disease with a focus on cancer. The lab pursues these goals by discovering and developing direct small-molecule probes of proteins involved in transcriptional regulation such as transcription factors and chromatin modifying enzymes.
Transcription factors that become overactive in disease are promising yet untested targets for therapeutics. For example, 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 been a significant challenge 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 in cells using 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. For example, the group is pursuing compounds that bind and modulate various B-cell master regulators including c-Myc, NF-κB and Pax5.
Transcription factors that become overactive in disease are promising yet untested targets for therapeutics. For example, 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 been a significant challenge 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 in cells using 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. For example, the group is pursuing compounds that bind and modulate various B-cell master regulators including c-Myc, NF-κB and Pax5.
研究兴趣
论文共 62 篇作者统计合作学者相似作者
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Annual Review of Cancer Biologyno. 1 (2024)
Mohammed A Toure, Keisuke Motoyama, Yichen Xiang, Julie Urgiles,Florian Kabinger, Ann-Sophie Koglin, Ramya S Iyer, Kaitlyn Gagnon, Amruth Kumar,Samuel Ojeda, Drew A Harrison,Matthew G Rees,
biorxiv(2024)
Catherine C. Henry, Jasmin A. Kruell,Robert M. Wilson,Chia-Fu Chang,Christina M. Woo,Angela N. Koehler
BIOCONJUGATE CHEMISTRYno. 12 (2023): 2181-2186
Mohammed A Toure,Angela N Koehler
Cell reportsno. 4 (2022): 110752-110752
biorxiv(2021)
Madeleine J. Henley,Angela N. Koehler
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