Our Research
The temporally specific and tissue specific expression of genotypes to phenotypes is a tightly regulated at the chromatin.
We use chemical tools to 1) expand the repertoire of chemical probes to study native protein interactions and 2) define chromatin remodeling and repair mechanisms in response to metabolic stress.
Chemical biology and quantitative mass spectrometry approaches are applied to generate functional predictions about chromatin maintenace and regulation. These observations are validated using biochemistry and cell-based experiments. Characterization of domain-specific interactions will serve to improve our fundamental understanding macromolecular recognition events, cancer development and serve as the basis for generating synthetic chemical probes, such as PROTACs, to modulate epigenetic activity driving development and progression of disease. The projects provide students with essential training in medicinal chemistry as they learn to think critically to address questions of chromatin homeostasis.
Chromatin Markers of DNA Damage
Elevated levels of reactive glycolysis intermediates lead to formation of toxic DNA-protein cross-links (DPCs) and is associated with cancer, diabetes and neurological diseases. We use biochemical and quantitative techniques to define DNA-protein interactions contributing to disease progression. In this work, students will define formation and repair kinetics of DNA-protein cross-links formed by metabolic by-products. These quantitative approaches will be used to assess disease risk and therapeutic interventions to limit formation of DNA lesions.
Protein-protein interactions driving disease progression
A major gap in knowledge in the field of epigenetics is an understanding of chemical motifs controlling protein-protein interactions. We will be designing, synthesizing, and deploying engineered protein-selective chimera ligands capable of tagging native protein interactions for characterization by quantitative mass spectrometry. Students will expand the use of these highly adaptable tools to identify and interrogate domain-specific interactions that mediate enzymatic activity driving development and progression of cancer.
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