The Liau Lab conducts research at the interface of chemical biology and genomics. Our lab is collaborative and multidisciplinary, combining organic chemistry, cell and molecular biology, protein biochemistry, and large-scale genetic screening to dissect molecular mechanisms underpinning biological processes, cancer mutations, and drug mechanism of action. One major research focus is understanding protein complexes that control genome function, with the long-term goal of defining and targeting functional sites, mechanisms, and dependencies for small molecule development.


CHEMICAL GENOMICS

 
 

Our group embraces next-generation genome editing tools for chemical genetic approaches. In one major direction, we have advanced CRISPR mutational scanning approaches to interrogate protein structure-function and small molecule mechanism of action. These approaches enable the broad and systematic identification of functional mutations across endogenous proteins of interest. We study key mutations in deeper mechanistic studies using any method at our disposal, enabling us to deconvolute small molecule mechanism, uncover sites of protein functionality and allosteric regulation, and identify new cancer dependencies. We have expanded these approaches to investigate entire multi-subunit complexes and pathways, implement new forms of precision genome-editing and single-cell technologies, and explore the mechanisms of diverse small molecule modalities. Ongoing efforts are focused on exploring chromatin complexes, transcription factors, signaling molecules, and E3 ubiquitin ligases. Our long-term goal is to leverage large-scale chemical-genomic maps with mechanistic insight for the development of therapeutic approaches.

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Gene Regulatory Complexes

 
 

We investigate the mechanisms of protein complexes that control genome function and transcription, using mutational scanning to identify their functional sites and chemical biology approaches to manipulate their activities and interactions. In particular, we have growing interests in studying transcription factors, their intertwined interactions with epigenetic regulators, and strategies to target their activities using small molecules.

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TECHNOLOGY DEVELOPMENT

 
 
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We are developing molecular biology tools leveraged with next-generation sequencing to study different layers of gene regulation. To enable these and other efforts, we are interested in the chemical synthesis of small molecules and their functional derivatives.

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