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Amy Barrios

Professor of Biochemistry

Professor of Medicinal Chemistry

Associate Dean of Postdoc Affairs

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

 

Links

Lab Page 

PubMed Literature Search

amy.barrios@utah.edu

 

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. “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  in press  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.
  2. “Inhibitor Screen Identifies Covalent Inhibitors of the Protein Histidine Phosphatase PHPT1” B. S. McCullough, H. Wang, A. M. Barrios ACS Med. Chem. Lett.202213(7), 1198-1201. https://doi.org/10.1021/acsmedchemlett.2c00053
  3. “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.2022, 13(5), 688-699.
  4. “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. 2021, 19, 10596-10600.
  5. “Histidine Phosphorylation in Metalloprotein Binding Sites” C. L. Mathis and A. M. BarriosJ. Inorg. Biochem.2021225, 111606.
  6. “PTPs: Degrading the Undruggable” A. M. BarriosJ. Med. Chem.2020, 63(14), 7508-7509.
  7. “Fluorogenic Probes for Imaging Cellular Phosphatase Activity” B. S. McCullough and A. M. BarriosCurr. Opin. Chem. Biol.2020, 57, 34-40.
  8. “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.
  9. “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. BarriosJ. Nat. Prod.2019 82, 3386-3393.
  10. “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.
  11. “Facile, Fluorogenic Assay for Protein Histidine Phosphatase Activity” B. S. McCullough and A. M. BarriosBiochem.2018 57(18), 2584-2589.
  12. “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.2017, 53, 4911-4914.
  13. “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.
  14. “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. Acta2015, 896, 160-165.
  15. “Marine Natural Products as Inhibitors of Cystathionine beta-Synthase Activity” M. K. Thorson, R. M. Van Wagoner, M. K. Harper, C. M. Ireland, T. Majtan, J. P. Kraus, A. M. BarriosBioorg. Med. Chem. Lett.2015, 25, 1064-1066.
  16. “Early Endosomal Escape of a Cyclic Cell-Penetrating Peptide Enables Effective Cytosolic Cargo Delivery” Z. Qian, J. LaRochelle, B. Jiang, W. Lian, R. Hard, N. G. Selner, R. Leuchapanichkul, A. M. Barrios, D. Pei Biochem. 2014 53(24), 4034-4046.
  17. “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. BarriosBioorg. Med. Chem. Lett.201424(16), 4019-4022.
  18. “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.
  19. “Monitoring Intracellular Protein Tyrosine Phosphatase Activity” S. M. Stanford, V. F. Ahmed, N. Bottini, A. M. BarriosAntioxidants and Redox Signaling 2014 20(14), 2160-2178.
  20. “Covalent Inhibition of the Lymphoid Tyrosine Phosphatase” V. F. Ahmed, N. Bottini & A. M. BarriosChemMedChem2014 9(2), 296-299. 
  21. “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.
  22. “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 201314(13), 1640-1647.
  23. “Thiuram Disulfides as Irreversible Inhibitors of the Lymphoid Tyrosine Phosphatase” R. A. Kulkarni, S. M. Stanford, N. A. Vellore, M. R. Bliss, D. Krishnamurthy, R. Baron, N. Bottini, A. M. BarriosChemMedChem 2013 8(9), 1561-1568.
  24. “Medicinal Inorganic Chemistry: a web themed issue” A. M. Barrios, S. M. Cohen, M. H. Lim Chem. Commun.2013 49, 5910-5911.
  25. “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.
  26. “Identification of Cystathionine beta-Synthase Inhibitors Using a Novel Hydrogen Sulfide Selective Probe” M. K. Thorson, T. Majtan, J. P. Kraus, A. M. BarriosAngew. Chem. 201352, 4641-4644.
  27. “Efficient Delivery of Cyclic Peptides into Mammalian Cells with Short Sequence Motifs” Z. Qian, T. Liu, Y.-Y. Liu, R. Briesewitz, A. M. Barrios, S. M. Jhiang, D. Pei ACS Chem. Biol.20138(2), 423-431.
  28. “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.2012, 109(35), 13972-13977.
Last Updated: 8/30/24