Raymond C Trievel
Professor of Biological Chemistry
Department of Biological Chemistry
1150 West Medical Center Drive
Ann Arbor, MI 48109
[email protected]

Available to mentor

Raymond C Trievel
Professor
  • About
  • Links
  • Qualifications
  • Center Memberships
  • Research Overview
  • Recent Publications
  • About

    Our laboratory uses a combination of structural and biochemical approaches to study the structures, substrate specificities, and mechanisms of a variety of enzymes, with a particular focus on enzymes involved in gene regulation. Techniques used in the lab include crystallography, enzymology, calorimetry and high throughput screening.

    Links
    • Trievel Laboratory
    Qualifications
    • NIH IRTA Postdoctoral Fellow
      National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2003
    • PhD
      University of Pennsylvania, Philadelphia, 2000
    • BS
      University of Delaware, Newark, 1995
    Center Memberships
    • Center Member
      Caswell Diabetes Institute
    Research Overview

    1) Structural and biochemical studies of chromatin modifying enzymes: Our laboratory utilizes biochemical and structural approaches to investigate the mechanisms of enzymes that catalyze chromatin modifications with a particular emphasis on SET domain lysine methyltransferases. We are also developing new assays and reagents that will facilitate high-throughput characterization of these enzymes. Our collective efforts are yielding insights into the molecular mechanisms underlying the establishment and maintenance of chromatin modification states and will furnish new avenues for developing novel therapeutics that target lysine methyltransferases to treat cancer and other protein methylation-linked diseases.

    2) Structural and functional characterization of Nocturnin, a deadenylase linked to obesity: Obesity is a growing worldwide epidemic that impacts the health and lifespan of affected individuals, increasing the risk of cardiovascular disease, high blood pressure, diabetes, and certain cancers. Discovering the underlying genetic and biochemical mechanisms that control metabolism and adipogenesis is fundamental to developing new therapeutics to combat this epidemic and to preventing diseases associated with obesity. Previous studies have revealed multiple genes in mammals that contribute to obesity, including the gene encoding Nocturnin. Mice bearing a knockout of the Nocturnin gene are resistant to diet-induced obesity, suggesting that this protein regulates specific genes that control fat uptake and metabolism. Nocturnin shares sequence homology with deadenylases that regulate the translation of mRNAs by degrading their 3' polyadenosine tails. In collaboration with Dr. Aaron Goldstrohm (University of Minnesota) and Dr. Peter Freddolino (UM Department of Biological Chemistry), we determined the first crystal structure of Nocturnin, revealing a protein fold and active site that is conserved in related deadenylases. Tethered function reporter assays demonstrate that Nocturnin represses translation in cells and that this repression is dependent on the structure of the 3' end of the mRNA. Together, these results demonstrate that Nocturnin functions as an exoribonuclease that can degrade mRNAs to inhibit protein expression and provide a foundation for elucidating Nocturnin’s biological functions in regulating fat metabolism and adipogenesis.

    3) Discovery and development of novel therapeutics to treat chronic kidney disease: Chronic kidney disease (CKD) ranks among the most common and deadly non-communicable degenerative diseases, affecting ~10% of the world population. At present there are no cures or medications available to combat CKD, and patients are typically treated through chronic dialysis or kidney transplants. To address this unmet clinical need, our laboratory is collaborating with Dr. Mathias Kretzler (UM Department of Internal Medicine), Dr. Jeanne Stuckey (UM Department of Biological Chemistry and the Life Sciences Institute), and Dr. Vincent Groppi (UM Center for the Discover of New Medicines and the Life Sciences Institute) to investigate a target for treating CKD. Our research team recently established an academic-industrial collaboration with AstraZeneca Pharmaceuticals with the overall goal of developing the first in class drug to treat CKD.

    Recent Publications See All Publications
    • Journal Article
      An optimized purification protocol for enzymatically synthesized S-adenosyl-L-methionine (SAM) for applications in solution state infrared spectroscopic studies.
      Odeyemi I, Douglas TA, Igie NF, Hargrove JA, Hamilton G, Bradley BB, Thai C, Le B, Unjia M, Wicherts D, Ferneyhough Z, Pillai A, Koirala S, Hagge LM, Polara H, Trievel RC, Fick RJ, Stelling AL. Spectrochim Acta A Mol Biomol Spectrosc, 2024 Mar 15; 309: 123816 DOI:10.1016/j.saa.2023.123816
      PMID: 38198991
    • Journal Article
      Intrinsic catalytic properties of histone H3 lysine-9 methyltransferases preserve monomethylation levels under low S-adenosylmethionine.
      Haws SA, Miller LJ, La Luz DR, Kuznetsov VI, Trievel RC, Craciun G, Denu JM. J Biol Chem, 2023 Jul; 299 (7): 104938 DOI:10.1016/j.jbc.2023.104938
      PMID: 37331600
    • Preprint
      Intrinsic catalytic properties of histone H3 lysine-9 methyltransferases preserve monomethylation levels under low S-adenosylmethionine
      Haws SA, Miller LJ, La Luz DR, Kuznetsov VI, Trievel RC, Craciun G, Denu JM. bioRxiv, DOI:10.1101/2022.09.09.507378
    • Journal Article
      EZH2 T367 phosphorylation activates p38 signaling through lysine methylation to promote breast cancer progression.
      Gonzalez ME, Naimo GD, Anwar T, Paolì A, Tekula SR, Kim S, Medhora N, Leflein SA, Itkin J, Trievel R, Kidwell KM, Chen Y-C, Mauro L, Yoon E, Andò S, Kleer CG. iScience, 2022 Aug 19; 25 (8): 104827 DOI:10.1016/j.isci.2022.104827
      PMID: 35992062
    • Presentation
      "Structure and Function of Legionella pneumophila Lysine Methyltransferases: How Bacteria Read and Write Histone Modifications"
      2022 Jul 1;
    • Journal Article
      Detection of cofactor conformer exchange in the active sites of methyltransferases with vibrational spectroscopy
      Bradley B, Hamilton G, Douglas T, Pillai A, Fick R, Hargrove D, Le B, Unjia M, Trievel R, Stelling A. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2022 May 1; 36: DOI:10.1096/fasebj.2022.36.S1.R2674
    • Journal Article
      H3K9me3 binding analysis of the isolated PHD and TTD domains of UHRF2
      Miller I, Khuansanguan P, Ginnard S, Winkler A, Heyl D, Trievel R. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2022 May 1; 36: DOI:10.1096/fasebj.2022.36.S1.R2539
    • Journal Article
      Investigating the structure of UHRF2 TTD-PHD with H3K9me3
      Konopka S, Trievel R, Albaugh B. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2022 May 1; 36: DOI:10.1096/fasebj.2022.36.S1.R3932