Metabolic Regulation of Epigenetic Signaling
Recent studies have shown that many enzymes active in epigenetic mechanisms of genomic regulation are sensitive to the metabolic state of the cell. A major aim of the lab is to understand the mechanisms by which metabolic perturbations influence genomic signaling mediated by chromatin modifying enzymes. Long term goals of this work include: 1) the discovery of biological mechanisms underlying oncometabolite-driven cancers, 2) the development of new diagnostics for cancers driven by metabolic mutations, and 3) the identification of small molecules which inhibit epigenetic modifications through metabolic disruption.
New Acetylation-Based Signaling Mechanisms
Acetyl-CoA links metabolism and signaling by mediating protein and nucleic acid modifications known as acetylations, whose modulation is an emerging paradigm in cancer treatment. A major focus of the laboratory is applying chemical approaches to discover and characterize new enzymatic and non-enzymatic acetylation mechanisms involved in fundamental biology and disease. By expanding the pharmacological map of acetylation-based signaling mechanisms in cancer, these studies aim to uncover new avenues for therapeutic development.
Fumarate Chemoproteomic Reactivity Database
To enable community efforts we have developed a web searchable database of FH-regulated cysteines identified by Kulkarni et al. (“A chemoproteomic portrait of the oncometabolite fumarate,” Nat. Chem Biol., 2019). It can be accessed at: https://ccr2.cancer.gov/resources/Cbl/Proteomics/Fumarate/
- Montgomery DC, Sorum AW, Meier JL. Chemoproteomic profiling of lysine acetyltransferases highlights an expanded landscape of catalytic acetylation. J Am Chem Soc. 2014;136(24):8669-76.
- Kang JS, Meier JL, Dervan PB. Design of sequence-specific DNA binding molecules for DNA methyltransferase inhibition. J Am Chem Soc. 2014;136(9):3687-94.
- Meier JL. Metabolic mechanisms of epigenetic regulation. ACS Chem Biol. 2013;8(12):2607-21.
- Meier JL, Yu AS, Korf I, Segal DJ, Dervan PB. Guiding the design of synthetic DNA-binding molecules with massively parallel sequencing. J Am Chem Soc. 2012;134(42):17814-22.
- Meier JL, Mercer AC, Rivera H Jr, Burkart MD. Synthesis and evaluation of bioorthogonal pantetheine analogues for in vivo protein modification. J Am Chem Soc. 2006;128(37):12174-84.
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This page was last updated on Friday, October 27, 2023