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Amy Barrios

Professor of Biochemistry

Professor of Medicinal Chemistry

Protein Phosphorylation, Chemical Probe Development, Metals in Medicine

Amy Barrios

 

Biological Chemistry Program

Education

B.S. University of Utah

Ph.D. Massachusetts Institute of Technology

 

Research

Despite the therapeutic relevance of many human protein phosphatases, our understanding of their biological substrates, substrate selectivity, cellular regulation and druggability is limited. Research in the Barrios lab focuses on addressing these challenges through the development and application of novel chemical probes, specifically 1) using fluorogenic probes to investigate protein phosphatase activity and regulation during cellular signaling, 2) investigating the impact of protein phosphorylation on structure and function and 3) identifying protein phosphatase inhibitors for use as therapeutic lead compounds. We are particularly interested in protein phosphatases involved in immune system dysregulation, cancer, and neurological disease. 

References (Selected Publications)

  1.  “An In Vitro Assay for Measuring Activity of Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase (LHPP)” E. D. Keyes, E. Starr, A. M. Barrios Invited submission for Histidine Phosphorylation Methods and Protocols, 2nd Edition; C. E. Eyers, Ed.; Methods in Molecular Biology in press.
  2.  “Inhibition of PHPT1 by Phenylarsonic Acids” E. D. Keyes, S. E. Hollow, P. Oblad, T. Johnstone, A. M. BarriosDalton Trans. 2026 55, 4196-4203. doi: 10.1039/d5dt03009a
  3. “Multipartite Fluorescent Sensors of Protein Tyrosine Phosphatase Activity” D. Hansen, J. Tu, A. W. Bouck, C. L. Mathis, A. M. BarriosChemBioChem 2024 25(24), e202400607. 10.1002/cbic.202400607 
  4.  “The Mechanism of Covalent Inhibition of LAR Phosphatase by Illudalic Acid” D. T. Hansen, N. J. Rueb, N. D. Levinzon, T. E. Cheatham, R. Gaston, Jr., Kh. T. Ahmed, S. Osburn-Staker, J. E. Cox, G. B. Dudley, A. M. BarriosBioorg. Med. Chem. Lett. 2024 (104), 129740
  5. “Gold(I) Ion and the Phosphine Ligand are Necessary for the anti-Toxoplasma gondii Activity of Auranofin.” C. I. Ma, J. A. Tirtorahardjo, S. S. Schweizer, J. Zhang, Z. Fang, L. Xing, M. Xu, D. Herman, M. T. Kleinman, B. S. McCullough, A. M. Barrios, R. M. Andrade. Microbiology Spectrum 2024 12(2), e0296823.
  6. “Derivatives of the Fungal Natural Product Illudalic Acid Inhibit the Activity of Protein Histidine Phosphatase PHPT1” H. Wang, R. Gaston, Jr., K. T. Ahmed, G. B Dudley, A. M. Barrios ChemMedChem 2023 18(15)e202300187 https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cmdc.202300187
    This article was highlighted in ChemistryViews (https://www.chemistryviews.org/new-inhibitors-based-on-illudalic-acid/) and selected for the cover of the print edition.
  7. “Inhibitor Screen Identifies Covalent Inhibitors of the Protein Histidine Phosphatase PHPT1” B. S. McCullough, H. Wang, A. M. Barrios ACS Med. Chem. Lett. 2022 13(7), 1198-1201. https://doi.org/10.1021/acsmedchemlett.2c00053
  8. “Small Molecules Targeting PTPs-Trk Interactions Promote Sympathetic Nerve Regeneration” M. R. Blake, R. T. Gardner, H. Jin, M. A. Staffenson, N. J. Rueb, A. M. Barrios, G. B. Dudley, M. S. Cohen, B. A. Habecker ACS Chem Neurosci. 202213(5), 688-699.
  9. “Synthesis of Illudalic Acid and Analogous Phosphatase Inhibitors” H. F. Fulo, N. J. Rueb, R. Gaston Jr., P. Batsomboon, K. T. Ahmed, A. M. Barrios, G. B. Dudley Org. & Biomol. Chem. 202119, 10596-10600.
  10. "Histidine Phosphorylation in Metalloprotein Binding Sites” C. L. Mathis and A. M. Barrios J. Inorg. Biochem. 2021 225, 111606.
  11. “PTPs: Degrading the Undruggable” A. M. Barrios J. Med. Chem. 202063(14), 7508-7509.
  12. “Fluorogenic Probes for Imaging Cellular Phosphatase Activity” B. S. McCullough and A. M. Barrios Curr. Opin. Chem. Biol. 202057, 34-40.
  13. In vitro Assays for Measuring Protein Histidine Phosphatase Activity” B. S. McCullough and A. M. Barrios In Histidine Phosphorylation Methods and Protocols; C. E. Eyers, Ed.; Methods in Molecular Biology 2077; Humana Press: New York, NY, 2020; 109-120
  14. “Synthesis and PTP inhibitory activity of illudalic acid and its methyl ether, with insights into selectivity for LAR PTP over other tyrosine phosphatases under physiologically relevant conditions” B. S. McCullough, P. Batsomboon, K. B. Hutchinson, G. B. Dudley and A. M. Barrios J. Nat. Prod. 2019 82, 3386-3393.
  15. “Rational design of a SHP-2 targeted, fluorogenic peptide substrate” E. S. Ma and A. M. Barrios Bioorg. Med. Chem. Lett. 2019 29(17), 2452-2454.
  16. “Facile, Fluorogenic Assay for Protein Histidine Phosphatase Activity” B. S. McCullough and A. M. Barrios Biochem. 2018 57(18), 2584-2589.
  17.  “A luminogenic lanthanide-based probe for the highly selective detection of nanomolar sulfide levels in aqueous samples” M. L. Aulsebrook, S. Biswas, F. M. Leaver, M. R. Grace, B. Graham, A. M. Barrios, K. L. Tuck Chem. Commun. 201753, 4911-4914.
  18. “Dual Colorimetric and Fluorogenic Probes for Visualizing Tyrosine Phosphatase Activity and High Throughput Screening” S. Biswas, B. S. McCullough, C. W. Russell, D. G. Brown, J. L. Round, M. A. Mulvey, A. M. BarriosChem. Commun. 2017, 53, 2233-2236.
  19. “Lanthanide complexes as luminogenic probes to measure sulfide levels in industrial samples” M. K. Thorson, P. Ung, F. M. Leaver, T. S. Corbin, K. L. Tuck*, B. Graham*, A. M. Barrios* Anal. Chim. Acta 2015, 896, 160-165. 
  20. “Inhibition of the Lymphoid Tyrosine Phosphatase: The Effect of Zinc(II) ions and Chelating Ligand Fragments on Enzymatic Activity” M. K. Thorson, D. T. Puerta, S. M. Cohen, A. M. Barrios Bioorg. Med. Chem. Lett. 2014 24(16), 4019-4022.
  21. “Auranofin is an Apoptosis Stimulating Agent with in vitro and in vivo Anti-Leishmanial Activity” E. Sharlow, S. Leimgruber, S. Murray, A. Lira, R. Sciotti, M. Hickman, T. Hudson, S. Leed, D. Caridha, A. M. Barrios, D. Close, M. Grogl, J. Lazo ACS Chem. Biol. 2014 9(3), 663-672.
  22. “pCAP-Based Peptide Substrates: The New Tool in the Box of Tyrosine Phosphatase Assays” S. M. Stanford, D. Krishnamurthy, C. E. Karver, E. Bruenger, L. Walker, C.-T. Ma, T. D. Y. Chung, E. Sergienko, N. Bottini, A. M. BarriosMethods 2014 65, 165-174.
  23.  “Substrate Selection Influences Molecular Recognition in a Screen for Lymphoid Tyrosine Phosphatase Inhibitors” R. A. Kulkarni, N. A. Vellore, M. R. Bliss, S. M. Stanford, M. D. Falk, N. Bottini, R. Baron, A. M. Barrios ChemBioChem 2013 14(13), 1640-1647.
  24. “A Potent and Selective Small Molecular Inhibitor for the Lymphocyte-Specific Tyrosine Phosphatase (LYP), a Common Risk Factor Associated with Autoimmune Diseases” Y. He, S. Liu, A. Menon, S. M. Stanford, E. Oppong, A. M. Gunawan, L. Wu, A. M. Barrios, N. Bottini, A. C. B. Cato, Z.-Y. Zhang J. Med. Chem, 2013 56(12) 4990-5008.
  25. “Identification of Cystathionine beta-Synthase Inhibitors Using a Novel Hydrogen Sulfide Selective Probe” M. K. Thorson, T. Majtan, J. P. Kraus, A. M. Barrios Angew. Chem. 2013 52, 4641-4644.
  26. “High-Throughput Screen Using a Single-Cell Tyrosine Phosphatase Assay Reveals Biologically Active CD45 Inhibitors” S. M. Stanford, R. G. Panchal, L. M. Walker, M. D. Falk, S. Mitra, S. S. Damle, D. Ruble, T. Kaltcheva, S. Zhang, Z.-Y. Zhang, S. Bavari, A. M. Barrios, N. Bottini Proc. Natl. Acad. Sci. 2012109(35), 13972-13977.
  27. “A High-Throughput Drug Screen for Entamoeba histolytica identifies a new lead and target” A. Debnath, D. Parsonage, R. Andrade, C. He, E. Cobo, K. Hirata, S. Chen, G. Garcia-Rivera, E. Orozco, M. Martinez, S. Gunatilleke, A. M. Barrios, M. Arkin, L. Poole, J. McKerrow, S. Reed Nat. Med. 201218(6), 956-960.
Last Updated: 7/30/26