Education, Honors, Awards

  • Assistant Professor, James Madison University, Harrisonburg, VA (2012-present)
  • Ruth L. Kirschstein National Research Service Award  (2009 – 2011)
  • Johns Hopkins University School of Medicine and the Howard Hughes Medical Institute (2008 – 2012)
  • Ph.D., Biomolecular Chemistry, University of Wisconsin-Madison School of Medicine, Madison, WI (2008)
  • American Heart Association Pre-Doctoral Fellow (2007 – 2008)
  • B.S., Chemistry, Roanoke College, Roanoke, VA (2003)

Research Interests

The effects of post-translational modification of protein lysine residues on cellular function focusing on:
  • Mechanistic enzymology of the modifying proteins
  • Chemical and Chemo-enzymatic methods to create substrates and/or inhibitors of modifying enzymes
  • X-ray crystallography to determine the structure of modifying enzymes and their substrates

Research Description

The presence of DNA damaging agents or moving from fed to fasting states requires the cell to respond to rapidly changing conditions. These changes require an efficient system to regulate the proteins that are involved in metabolism, damage repair, and the cell cycle. Rather than transcribe and translate a new protein in response to a new stimulus (which is VERY slow!), cells modify the amino acid side chains of existing proteins with chemical tags, resulting in a rapid change of protein function. The Berndsen lab studies the enzymes that catalyze modification of protein lysine side chains with ubiquitin, which is a protein, and lysine acetyltransferases (KATs).  Defects in acetylation and ubiquitination are linked to anemia, insomnia, and cancer therefore knowledge of the catalytic mechanism provides insight into the biochemical basis of these syndromes.  
 
We study the chemical mechanism of the ubiquitination and acetyltransfer enzymes through biochemical assays of protein function, X-ray crystallography and NMR of the protein structure, computer modeling, and other biochemical and biophysical techniques. 
 
A second project involves the protein Tetherin, which alters viral release from cells.  The activity of Tetherin has been linked to HIV, Ebola, Influenza, Herpes and other enveloped viruses.  We aim to study the structure of Tetherin and how viral proteins antagonize this structure leading to blocking of Tetherin's anti-viral budding activity.
 

Selected Recent Publications

  • Berndsen CE, Wolberger C. "New insights into ubiquitin E3 ligase mechanism." Nat Struct Mol Biol. 2014 Apr;21(4):301-7. doi: 10.1038/nsmb.2780. 
  • Taylor MS, Ruch TR, Hsiao PY, Hwang Y, Zhang P, Dai L, Huang CR, Berndsen CE, Kim MS, Pandey A, Wolberger C, Marmorstein R, Machamer C, Boeke JD, Cole PA. "Architectural organization of the metabolic regulatory enzyme ghrelin O-acyltransferase."  J Biol Chem. 2013 Nov 8;288(45):32211-28. doi: 10.1074/jbc.M113.510313.
  • Berndsen CE, Wiener R, Yu IW, Ringel AE, Wolberger C.  "A conserved asparagine has a structural role in ubiquitin-conjugating enzymes."  Nat Chem Biol. 2013 Mar;9(3):154-6. doi: 10.1038/nchembio.1159.
  • Guzzo CM, Berndsen CE, Zhu J, Gupta V, Datta A, Greenberg RA, Wolberger C, Matunis MJ.  "RNF4-dependent hybrid SUMO-ubiquitin chains are signals for RAP80 and thereby mediate the recruitment of BRCA1 to sites of DNA damage." Sci Signal. 2012 Dec 4;5(253):ra88. doi: 10.1126/scisignal.2003485.
  • Andrew AJ, Berndsen CE, Kao S, Strebel K. "The size and conservation of a coiled-coil structure in the ectodomain of human BST-2/tetherin is dispensable for inhibition of HIV-1 virion release."  J Biol Chem. 2012 Dec 28;287(53):44278-88. doi: 10.1074/jbc.M112.418822.
  • Berndsen CE, Wolberger C., "A spectrophotometric assay for conjugation of ubiquitin and ubiquitin-like proteins." (2011) Anal Biochem. Nov 1;418(1):102-10.
  • Samara NL, Datta AB, Berndsen CE, Zhang X, Yao T, Cohen RE, Wolberger C. "Structural insights into the assembly and function of the SAGA deubiquitinating module." (2010Science. May 21;328(5981):1025-9.
  • Berndsen CE, Tsubota T, Lindner SE, Lee S, Holton JM, Kaufman PD, Keck JL, Denu JM. "Molecular functions of the histone acetyltransferase chaperone complex Rtt109-Vps75." (2008Nat Struct Mol Biol. Sep;15(9):948-56.
  • Tsubota T, Berndsen CE, Erkmann JA, Smith CL, Yang L, Freitas MA, Denu JM, Kaufman PD. "Histone H3-K56 acetylation is catalyzed by histone chaperone-dependent complexes. " (2007) Mol Cell. Mar 9;25(5):703-12.
  • Berndsen CE, Selleck W, McBryant SJ, Hansen JC, Tan S, Denu JM. "Nucleosome recognition by the Piccolo NuA4 histone acetyltransferase complex." (2007) Biochemistry Feb 27;46(8):2091-9.
  • Berndsen CE, Albaugh BN, Tan S, Denu JM. "Catalytic mechanism of a MYST family histone acetyltransferase. " (2007) Biochemistry Jan 23;46(3):623-9.

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