Barbara J. Graves, Ph.D.

Research Interests

  • Signal Transduction
  • ETS Family
  • Transcription
  • DNA-Protein Interactions

Labs

Lab Website

Languages

  • English

Academic Information

  • Departments: Oncological Sciences - Professor
  • Cancer Center Programs: Nuclear Control of Cell Growth & Differentiation

Academic Office Information

  • (801) 581-7308
  • Huntsman Cancer Institute
    2000 Circle of Hope, Room: 4380
    Salt Lake City, UT 84112

Research Statement

We have set as a long-term goal to understand how a family of highly related DNA binding factors is utilized in biological regulation using the ETS family as a model system. Do individual ETS proteins have unique roles or are there redundancies of function within the family? Specificity would require both a divergence of functionality of individual family members as well as pathways to direct different family members to different gene promoter targets. There is extensive co-expression of ETS family members in a diverse sampling of human cell types. Genome-wide analysis of promoter targets in several of the cell types shows that, in some cases, there is specific matching between specific ETS proteins and specific targets. In other cases, there is co-occupancy by multiple ETS proteins at a specific promoter. We are currently investigating mechanisms of specificity for multiple family members including Ets-1, ETV6, ETV1, ETV4 and ETV5.

Academic Bio

Barbara Graves, PhD, is professor of the Department of Oncological Sciences at the University of Utah School of Medicine. She is a member of the Nuclear Control Program of the Huntsman Cancer Institute. Dr. Graves joined the faculty of the University of Utah in 1986 in the Department of Cellular, Viral and Molecular Biology. Upon the foundation of the Huntsman Cancer Institute in 1994 she became one of the founding members of the Department of Oncological Sciences. She served as Department Chair for 10 years as well as Senior Director for Basic Science at HCI for 4 years. Graves research focuses on how genes are turned on and off by regulatory proteins called transcription factors. Transcription is the process by which genetic code information passes from one cell to another. This gene expression process is essential for normal cell behavior and often goes awry in a cancer cell. A thorough understanding of how transcription factors and other molecular mechanisms control gene expression can lead to innovative new therapies and treatments for a variety of cancers. Graves's current focus is ETS transcription factors which are altered in human sarcomas, prostate cancer, and a variety of hematological malignancies.A graduate of Rice University, Graves earned her PhD from the University of Washington and completed postdoctoral training at the Fred Hutchinson Cancer Center and the Carnegie Institute of Washington. Dr. Graves currently spends part of her time in the Washington, DC area serving as a Senior Scientific Officer of the Howard Hughes Medical Institute.

Education History

Type School Degree
Postdoctoral Fellowship Carnegie Institution
Molecular Biology
Postdoctoral Fellow
Postdoctoral Fellowship Fred Hutchinson Cancer Research Center
Molecular Biology
Postdoctoral Fellow
Doctoral Training University of Washington
Developmental Biology
Ph.D.
Undergraduate Rice University
Biology
B.A.

Selected Publications

Journal Article

  1. Autoinhibition of ETV6 DNA Binding Is Established by the Stability of Its Inhibitory Helix.De S, Okon M, Graves BJ, McIntosh LP (2016). Autoinhibition of ETV6 DNA Binding Is Established by the Stability of Its Inhibitory Helix. J Mol Biol, 428(8), 1515-30.
  2. Conformational Dynamics and the Binding of Specific and Nonspecific DNA by the Autoinhibited Transcription Factor Ets-1.Desjardins G, Okon M, Graves BJ, McIntosh LP (2016). Conformational Dynamics and the Binding of Specific and Nonspecific DNA by the Autoinhibited Transcription Factor Ets-1. Biochemistry, 55(29), 4105-18.
  3. Synergy of aromatic residues and phosphoserines within the intrinsically disordered DNA-binding inhibitory elements of the Ets-1 transcription factor.Desjardins G, Meeker CA, Bhachech N, Currie SL, Okon M, Graves BJ, McIntosh LP (2014). Synergy of aromatic residues and phosphoserines within the intrinsically disordered DNA-binding inhibitory elements of the Ets-1 transcription factor. Proc Natl Acad Sci U S A, 111(30), 11019-24.
  4. Autoinhibition of ETV6 (TEL) DNA binding: appended helices sterically block the ETS domain.Coyne HJ 3rd, De S, Okon M, Green SM, Bhachech N, Graves BJ, McIntosh LP (2012). Autoinhibition of ETV6 (TEL) DNA binding: appended helices sterically block the ETS domain. J Mol Biol, 421(1), 67-84.
  5. Oncogenic ETS proteins mimic activated RAS/MAPK signaling in prostate cells.Hollenhorst PC, Ferris MW, Hull MA, Chae H, Kim S, Graves BJ (2011). Oncogenic ETS proteins mimic activated RAS/MAPK signaling in prostate cells. Genes Dev, 25(20), 2147-57.
  6. DNA binding by the ETS protein TEL (ETV6) is regulated by autoinhibition and self-association.Green SM, Coyne HJ 3rd, McIntosh LP, Graves BJ (2010). DNA binding by the ETS protein TEL (ETV6) is regulated by autoinhibition and self-association. J Biol Chem, 285(24), 18496-504.
  7. Simon L Currie, Desmond K Lau, Jedediah J Doane, Frank G Whitby, Mark Okon, Lawrence P McIntosh, and Barbara J Graves (In Press). Structured and disordered regions cooperatively mediate DNA-binding autoinhibition of ETS factors ETV1, ETV4, and ETV5. Nucleic Acids Res.

Review

  1. Genomic and biochemical insights into the specificity of ETS transcription factors.Hollenhorst PC, McIntosh LP, Graves BJ (2011). Genomic and biochemical insights into the specificity of ETS transcription factors. [Review]. Annu Rev Biochem, 80, 437-71.