Cynthia Wolberger, Ph.D.

Headshot of Cynthia Wolberger
  • Director of the Department of Biophysics and Biophysical Chemistry
  • Professor of Biophysics and Biophysical Chemistry

Research Interests

Mechanism of ubiquitin signaling in transcription and the DNA damage response; Structural and biochemical studies of enzyme complexes involved in ubiquitin signaling and chromatin modification; cross-talk between histone modifications. ...read more

Background

Dr. Cynthia Wolberger holds the Brown Advisory Colleagues Professorship in Scientific Innovation. She is Director and Professor of the Department of Biophysics and Biophysical Chemistry at the Johns Hopkins University School of Medicine. Her research focuses on structural biology, ubiquitin signaling and regulation of transcription.

Dr. Wolberger received her undergraduate degree in physics from Cornell University and earned her Ph.D. in biophysics at Harvard University. She completed postdoctoral work at the University of California, San Francisco, and the Johns Hopkins School of Medicine. Dr. Wolberger joined the Johns Hopkins faculty in 1991.

Dr. Wolberger studies how DNA packaging proteins—which coil DNA into neat, compact bundles in the cell—turn genes on or off, or initiate broken DNA repair. These DNA packaging proteins, aka histones, are called to action by the addition of chemical tags, like ubiquitin protein or acetyl chemical groups. To determine the structure of the histones and which chemical tags they use, Dr. Wolberger employs x-ray crystallography and cryo-electron microscopy, techniques that allows researchers to develop three-dimensional models of proteins.

Dr. Wolberger is a member of the National Academy of Sciences and the American Academy of Arts and Sciences. She is also a Fellow of the American Association for the Advancement of Science and of the Biophysical Society. She has been recognized with the Dorothy Crowfoot Hodgkin Award by The Protein Society for her work in determining the structure of proteins involved in transcriptional regulation.

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Titles

  • Director of the Department of Biophysics and Biophysical Chemistry
  • Brown Advisory Colleagues Professor in Scientific Innovation
  • Professor of Biophysics and Biophysical Chemistry
  • Professor of Oncology

Departments / Divisions

  • Biophysics and Biophysical Chemistry
  • Oncology

Centers & Institutes

Education

Degrees

  • A.B.; Cornell University (New York) (1979)
  • Ph.D.; Harvard University (Massachusetts) (1987)

Additional Training

  • University of California, San Francisco, CA, 1989; Johns Hopkins School of Medicine, Baltimore, MD, 1991

Research & Publications

Research Summary

Dr. Wolberger and her lab are interested in the structural and mechanistic basis for transcriptional regulation and ubiquitin signaling. Protein function is dynamically regulated in the cell by the attachment and subsequent removal of covalent posttranslational modifications. Acetylation and ubiquitination both occur in chromatin, the nucleoprotein complex into which eukaryotic DNA is packaged. Acetylation of the histone proteins in chromatin is associated with activation of transcription, whereas ubiquitination can be either an activating or a repressive mark, depending on which histone protein is modified. Ubiquitination of chromatin also plays a role in the response to DNA double-strand breaks, helping to recruit proteins that are required for DNA repair. They are interested in the molecular basis for these events, which ensure the integrity and expression of the genome. They use x-ray crystallography, enzymology, and a variety of biophysical tools to gain insights into the mechanisms underlying these essential cellular processes.

Lab

Lab Website: Wolberger Lab

Selected Publications

View all on PubMed

Worden EJ, Zhang X, Wolberger C. (2020) Structural basis for COMPASS recognition of an H2B-ubiquitinated nucleosome. Elife. 2020 Jan 10;9. pii: e53199. doi: 10.7554/eLife.53199

Worden EJ, Hoffmann N, Wolberger C. (2019) Mechanism of cross-talk between H2B ubiquitination and H3 methylation by Dot1L. Cell, 176(6):1490-1501

Morgan M, Haj-Yahya M, Ringel AE, Bandi P, Brik A, Wolberger C. (2016) Structural basis for histone H2B deubiquitination by the SAGA DUB module. Science 351:725-8

Wiener R, Zhang X, Wang T, Wolberger C. (2012) The mechanism of OTUB1-mediated inhibition of ubiquitination. Nature. 483:618-22

Samara NL, Datta AB, Berndsen CE, Zhang X, Yao T, Cohen RE, Wolberger C (2010) Structural insights into the assembly and function of the SAGA deubiquitinating module. Science 328: 1025-1029

Contact for Research Inquiries

725 N. Wolfe Street
714 WBSB
Baltimore, MD 21205 map
Phone: 410-955-0728

Email me

Academic Affiliations & Courses

Graduate Program Affiliation

Program in Biochemistry, Cellular and Molecular Biology (BCMB)

Program in Molecular Biophysics (PMB)

Chemistry-Biology Interface (CBI)

Activities & Honors

Honors

  • Received A.B. cum laude in Physics and With Distinction in all subjects, 1979
  • Damon Runyon - Fund Fellow, Walter Winchell Cancer Research, 1987 - 1990
  • David and Lucile Packard Fellowship for Science and Engineering, 1992 - 1997
  • Basil O’Connor Starter Scholar Award, March of Dimes, 1992 - 1994
  • Junior Faculty Award, American Cancer Society , 1993 - 1994
  • Howard Hughes Medical Institute Investigator, 1994 - 2004
  • Dorothy Crowfoot Hodgkin Award, Protein Society, 2013
  • Member, National Academy of Sciences, 2019
  • Member, American Academy of Arts and Sciences, 2019
  • Fellow, Biophysical Society, 2020
  • Award for Outstanding Achievement in Chemistry in Cancer Research, American Association for Cancer Research, 2021

Memberships

  • American Association for the Advancement of Science
  • American Crystallographic Association
  • American Society for Biochemistry and Molecular Biology
  • Biophysical Society
  • Protein Society

Professional Activities

  • Board on Life Sciences, National Academy of Sciences, 2007 - 2013
  • Chair, RCSB Protein Data Bank Advisory Committee, 2012
  • Editorial board, Current Opinions in Structural Biology, 2012
  • Editorial board, Protein Science, 2011
  • Editorial board, Annual Reviews in Biophysics, 2004 - 2013
  • Faculty of 1000 section head, Transcription and Translation, 2001
  • Molecular Biophysics Advisory Panel, National Science Foundation, 1996 - 2001
  • Senior editor, eLife, 2018

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