Ray Trievel

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Assistant Professor of Biological Chemistry

Office Location(s): 4412 Medical Science Building I
Phone: 734.647.0889
rtrievel@umich.edu

  • About

    Post-translational modifications of proteins play pivotal roles in governing a myriad of biological functions within the cell. Gene expression, the cell cycle, intracellular signaling cascades, cytoskeletal organization, and numerous metabolic pathways are just a few examples of cellular functions that are controlled by covalent modifications. Our laboratory is interested in understanding how protein modifications within the nucleus impact transcription and other genomic processes. Histones, the major scaffolding proteins that organize genomic DNA in chromatin, are enriched in modifications such as acetylation, methylation, phosphorylation and ubiquitination. Transcription factors and other components of the transcriptional machinery are subject to similar types of covalent modifications in vivo. These modifications collectively act as molecular switches that can either activate or repress gene expression, depending on the pattern of modifications established within a given gene locus. Aberrant histone modifications have been directly linked to carcinogenesis, underscoring the fundamental importance of these pathways in governing faithful gene expression.

    Our laboratory is currently investigating histone lysine methyltransferases (HKMTs), a group of enzymes that epigenetically regulate transcription, heterochromatin structure, DNA damage checkpoints, development, differentiation, and the cell cycle. Using structural and biochemical techniques, we have characterized the molecular basis of substrate recognition for several representative HKMTs in order to elucidate the mechanisms by which they catalyze site-specific lysine methylation in histones and other nuclear proteins. A thorough understanding of these specificities is critical to human health because aberrant HKMT activity has been clinically documented in a broad spectrum of cancers, including prostate, breast, lung, hepatic, and colorectal cancers. We envision that our research will enable us to develop HKMT inhibitors as novel chemotherapeutic agents and will also impact gene therapy and stem cell research due to the central importance of gene regulation to these fields.

  • Education
    • Ph.D., University of Pennsylvania
  • Selected Publications:
  • Articles