Barbara J. Graves

Barbara J. Graves, PhD

Languages spoken: English

Academic Information

Departments Emeritus - Oncological Sciences

Lab

Research Interests

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

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.

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.

Education History

Postdoctoral Fellowship Carnegie Institution
 Postdoctoral Fellow
Postdoctoral Fellowship Fred Hutchinson Cancer Research Center
 Postdoctoral Fellow
Doctoral Training University of Washington
 PhD
Undergraduate Rice University
 BA

Selected Publications

Journal Article

  1. 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. (Epub ahead of print) Nucleic Acids Res.
  2. Perez-Borrajero C, Lin CS, Okon M, Scheu K, Graves BJ, Murphy MEP, McIntosh LP (2018). The Biophysical Basis for Phosphorylation-Enhanced DNA-Binding Autoinhibition of the ETS1 Transcription Factor. J Mol Biol, 431(3), 593-614. (Read full article)
  3. Currie SL, Warner SL, Vankayalapati H, Liu X, Sharma S, Bearss DJ, Graves BJ (2018). Development of High-Throughput Screening Assays for Inhibitors of ETS Transcription Factors. SLAS Discov, 24(1), 77-85. (Read full article)
  4. Madison BJ, Clark KA, Bhachech N, Hollenhorst PC, Graves BJ, Currie SL (2018). Electrostatic repulsion causes anticooperative DNA binding between tumor suppressor ETS transcription factors and JUN-FOS at composite DNA sites. J Biol Chem, 293(48), 18624-18635. (Read full article)
  5. Currie SL, Doane JJ, Evans KS, Bhachech N, Madison BJ, Lau DKW, McIntosh LP, Skalicky JJ, Clark KA, Graves BJ (2017). ETV4 and AP1 Transcription Factors Form Multivalent Interactions with three Sites on the MED25 Activator-Interacting Domain. J Mol Biol, 429(20), 2975-2995. (Read full article)
  6. Currie SL, Lau DKW, Doane JJ, Whitby FG, Okon M, McIntosh LP, Graves BJ (2016). Structured and disordered regions cooperatively mediate DNA-binding autoinhibition of ETS factors ETV1, ETV4 and ETV5. Nucleic Acids Res, 45(5), 2223-2241. (Read full article)
  7. 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. (Read full article)
  8. 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. (Read full article)
  9. 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. (Read full article)
  10. 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. (Read full article)
  11. 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. (Read full article)
  12. 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. (Read full article)
  13. Seidel JJ, Graves BJ (2002). An ERK2 docking site in the Pointed domain distinguishes a subset of ETS transcription factors. Genes Dev, 16(1), 127-37. (Read full article)

Review

  1. 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. (Read full article)