Amy M. Barrios

Last updated
Amy M. Barrios
Born
Salt Lake City, Utah, US
NationalityAmerican
Education
Occupation(s)Associate Dean for Postdoctoral Affairs, University of Utah
Website https://pharmacy.utah.edu/medchem/faculty/barrios-lab/

Amy M. Barrios is an American medicinal chemist working as a professor of Medicinal Chemistry and the Associate Dean for Postdoctoral Affairs for the University of Utah. [1] Barrios' research lab focuses on developing probes to study protein tyrosine phosphatase (PTP) activity and regulation.

Contents

Education

Amy Barrios graduated with her bachelor's degree in chemistry from the University of Utah in 1995, where she worked as an undergraduate researcher in the Department of Radiobiology under Scott C. Miller. [2] Barrios received the Hypercube Scholar Award from the University of Utah in 1995. She then attended graduate school at the Massachusetts Institute of Technology and received her Ph.D. in Inorganic Chemistry. In graduate school, she worked with Stephen J. Lippard [3] as her research advisor. She was awarded an NIH Predoctoral Fellowship at MIT, still working with Lippard, and then was awarded an NIH Postdoctoral Fellowship at the University of California, San Francisco working with Charles S. Craik. [4]

Career and research

Barrios started her career as an undergraduate researcher in the Department of Radiobiology under Professor Scott C. Miller [2] at the University of Utah. In this lab, she researched radiation poisoning toward the development of an oral medication that could bind to radioactive molecules to take out of the body. She continued her research career during her Ph.D. under Professor Stephen J. Lippard, [3] in the Department of Chemistry at MIT. At MIT, she worked on the metalloenzyme urease and created a compound to understand how the di-nickel center in urease hydrolyzes urea since the mechanism of action had not yet been discovered. While the synthetic compound allowed Barrios to determine the mechanism of action, this mechanism turned out to be similar to, but not the same, as the mechanism that urease uses. She worked on additional metalloenzymes that used iron and nickel during her graduate work. [5]

During her postdoctoral fellowship at the University of California under Professor Charles S. Craik, [4] she developed a method to assay the substrate specificity of proteolytic enzymes using lanthanide ion fluorescence. This method was used to develop peptide libraries to determine substrate specificity for proteolytic enzymes.

While at the University of Southern California as a Gabilan Assistant Professor of Chemistry, Barrios worked on a tool that allows the visualization of tyrosine phosphatase activity in cells in real-time using protein tyrosine phosphatases (PTPs). [6] This activity was used to determine and isolate cell-permeable inhibitors of PTPs that could be used as potential drugs later on, for example, working on CD45 and Bacillus anthracis. Related to this work on PTPs, in 2006, Barrios and Sayantan Mitra filed a patent for "Coumarin-based amino acids for used in enzyme activity and substrate specificity assay" which can be incorporated into peptides to visualize the hydrolyzation of PTPs. Additionally, in 2009, Barrios, Mitra, Stephanie Stanford, and Nunzio Bottini filed a patent for a "Method for monitoring intracellular tyrosine phosphatase activity". This invention was based on the CD45 probe used in the previously mentioned tyrosine phosphatases and is used to monitor "intracellular tyrosine dephosphorylation at the single-cell level" [7] and the potential development of novel therapeutics.

As assistant professor of Medicinal Chemistry at the University of Utah in 2012, Barrios worked on a drug to target a parasite known as Entamoeba histolytica. This parasite causes amebiasis which was the fourth leading cause of death world-wide caused by protozoan infections. [8] Metronidazole, the drug that was being used at the time, had adverse side effects and some resistance to the medication was on the rise. Barrios contributed to the development of a new anti-parasitic drug. Through a high-throughput drug screen, they found that auranofin, which is commonly used for rheumatoid arthritis, targets TrxR which decreases the parasite's ability to withstand oxidative stress. This research provided a new drug that could serve as a new treatment for amebiasis caused by the Entamoeba histolytica. [9] In 2017, auranofin completed phase I clinical trials against Entamoeba histolytica and Giardia [10]

The Barrios Lab in the Department of Pharmacy at the University of Utah largely focuses on developing chemical probes to study biological substrates, substrate selectivity, cellular regulation, and druggability for use in therapeutics. Human protein tyrosine phosphatases (PTPs) hold substantial relevance in human autoimmunity and T-cell receptor signaling, as well as cell signaling in diseases. Novel chemical probes to better understand the activity and regulation of this family of enzymes aids in developing human therapeutics. [11] These developments in the Barrios Lab include fluorogenic probes to investigate PTP activity, [12] along with profiling substrate selectivity for the use of developing potent, selective inhibitors. Additionally, the Barrios Lab also focuses on chemical tools used to study the therapeutic roles of metal ions as biological targets of gold-based compounds.

Awards and honors

Bibliography

Related Research Articles

A protein phosphatase is a phosphatase enzyme that removes a phosphate group from the phosphorylated amino acid residue of its substrate protein. Protein phosphorylation is one of the most common forms of reversible protein posttranslational modification (PTM), with up to 30% of all proteins being phosphorylated at any given time. Protein kinases (PKs) are the effectors of phosphorylation and catalyse the transfer of a γ-phosphate from ATP to specific amino acids on proteins. Several hundred PKs exist in mammals and are classified into distinct super-families. Proteins are phosphorylated predominantly on Ser, Thr and Tyr residues, which account for 79.3, 16.9 and 3.8% respectively of the phosphoproteome, at least in mammals. In contrast, protein phosphatases (PPs) are the primary effectors of dephosphorylation and can be grouped into three main classes based on sequence, structure and catalytic function. The largest class of PPs is the phosphoprotein phosphatase (PPP) family comprising PP1, PP2A, PP2B, PP4, PP5, PP6 and PP7, and the protein phosphatase Mg2+- or Mn2+-dependent (PPM) family, composed primarily of PP2C. The protein Tyr phosphatase (PTP) super-family forms the second group, and the aspartate-based protein phosphatases the third. The protein pseudophosphatases form part of the larger phosphatase family, and in most cases are thought to be catalytically inert, instead functioning as phosphate-binding proteins, integrators of signalling or subcellular traps. Examples of membrane-spanning protein phosphatases containing both active (phosphatase) and inactive (pseudophosphatase) domains linked in tandem are known, conceptually similar to the kinase and pseudokinase domain polypeptide structure of the JAK pseudokinases. A complete comparative analysis of human phosphatases and pseudophosphatases has been completed by Manning and colleagues, forming a companion piece to the ground-breaking analysis of the human kinome, which encodes the complete set of ~536 human protein kinases.

<span class="mw-page-title-main">Protein tyrosine phosphatase</span> Class of enzymes

Protein tyrosine phosphatases (EC 3.1.3.48, systematic name protein-tyrosine-phosphate phosphohydrolase) are a group of enzymes that remove phosphate groups from phosphorylated tyrosine residues on proteins:

<span class="mw-page-title-main">Phytase</span> Class of enzymes

A phytase is any type of phosphatase enzyme that catalyzes the hydrolysis of phytic acid – an indigestible, organic form of phosphorus that is found in many plant tissues, especially in grains and oil seeds – and releases a usable form of inorganic phosphorus. While phytases have been found to occur in animals, plants, fungi and bacteria, phytases have been most commonly detected and characterized from fungi.

<span class="mw-page-title-main">Receptor tyrosine kinase</span> Class of enzymes

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins. Receptor tyrosine kinases have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Mutations in receptor tyrosine kinases lead to activation of a series of signalling cascades which have numerous effects on protein expression. The receptors are generally activated by dimerization and substrate presentation. Receptor tyrosine kinases are part of the larger family of protein tyrosine kinases, encompassing the receptor tyrosine kinase proteins which contain a transmembrane domain, as well as the non-receptor tyrosine kinases which do not possess transmembrane domains.

<span class="mw-page-title-main">Auranofin</span> Chemical compound

Auranofin is a gold salt classified by the World Health Organization as an antirheumatic agent. It has the brand name Ridaura.

<span class="mw-page-title-main">PTPRC</span> Mammalian protein found in Homo sapiens

Protein tyrosine phosphatase, receptor type, C also known as PTPRC is an enzyme that, in humans, is encoded by the PTPRC gene. PTPRC is also known as CD45 antigen, which was originally called leukocyte common antigen (LCA).

<i>para</i>-Nitrophenylphosphate Chemical compound

para-Nitrophenylphosphate (pNPP) is a non-proteinaceous chromogenic substrate for alkaline and acid phosphatases used in ELISA and conventional spectrophotometric assays. Phosphatases catalyze the hydrolysis of pNPP liberating inorganic phosphate and the conjugate base of para-nitrophenol (pNP). The resulting phenolate is yellow, with a maximal absorption at 405 nm. This property can be used to determine the activity of various phosphatases including alkaline phosphatase (AP) and protein tyrosine phosphatase (PTP).

<span class="mw-page-title-main">ACP1</span> Protein-coding gene in humans

Low molecular weight phosphotyrosine protein phosphatase is an enzyme that in humans is encoded by the ACP1 gene.

<span class="mw-page-title-main">Methionine gamma-lyase</span>

The enzyme methionine γ-lyase (EC 4.4.1.11, MGL) is in the γ-family of PLP-dependent enzymes. It degrades sulfur-containing amino acids to α-keto acids, ammonia, and thiols:

<span class="mw-page-title-main">PTPN12</span> Protein-coding gene in the species Homo sapiens

Tyrosine-protein phosphatase non-receptor type 12 is an enzyme that in humans is encoded by the PTPN12 gene.

<span class="mw-page-title-main">PTPRA</span> Protein-coding gene in the species Homo sapiens

Receptor-type tyrosine-protein phosphatase alpha is an enzyme that in humans is encoded by the PTPRA gene.

<span class="mw-page-title-main">PTPN2</span> Protein-coding gene in the species Homo sapiens

Tyrosine-protein phosphatase non-receptor type 2 is an enzyme that in humans is encoded by the PTPN2 gene.

<span class="mw-page-title-main">PTPRN</span> Protein-coding gene in the species Homo sapiens

Receptor-type tyrosine-protein phosphatase-like N, also called "IA-2", is an enzyme that in humans is encoded by the PTPRN gene.

<span class="mw-page-title-main">PTPRM</span> Protein-coding gene in the species Homo sapiens

Receptor-type tyrosine-protein phosphatase mu is an enzyme that in humans is encoded by the PTPRM gene.

<span class="mw-page-title-main">PTPRU</span> Protein-coding gene in the species Homo sapiens

Receptor-type tyrosine-protein phosphatase PCP-2, is an enzyme that in humans is encoded by the PTPRU gene.

<span class="mw-page-title-main">PTPRK</span> Protein-coding gene in the species Homo sapiens

Receptor-type tyrosine-protein phosphatase kappa is an enzyme that in humans is encoded by the PTPRK gene. PTPRK is also known as PTPkappa and PTPκ.

<span class="mw-page-title-main">PTPRT</span> Protein-coding gene in the species Homo sapiens

Receptor-type tyrosine-protein phosphatase T is an enzyme that in humans is encoded by the PTPRT gene.

<span class="mw-page-title-main">PTPN5</span> Protein-coding gene in the species Homo sapiens

Protein tyrosine phosphatase non-receptor type 5 is an enzyme that in humans is encoded by the PTPN5 gene.

<span class="mw-page-title-main">Stephen J. Lippard</span> American chemist

Stephen James Lippard is the Arthur Amos Noyes Emeritus Professor of Chemistry at the Massachusetts Institute of Technology. He is considered one of the founders of bioinorganic chemistry, studying the interactions of nonliving substances such as metals with biological systems. He is also considered a founder of metalloneurochemistry, the study of metal ions and their effects in the brain and nervous system. He has done pioneering work in understanding protein structure and synthesis, the enzymatic functions of methane monooxygenase (MMO), and the mechanisms of cisplatin anticancer drugs. His work has applications for the treatment of cancer, for bioremediation of the environment, and for the development of synthetic methanol-based fuels.

<span class="mw-page-title-main">YopH, N-terminal</span>

In molecular biology, YopH, N-terminal refers to an evolutionary conserved protein domain. This entry represents the N-terminal domain of YopH protein tyrosine phosphatase (PTP).

References

  1. ↑ "Amy Barrios". University of Utah College of Pharmacy.
  2. 1 2 "Scott C. Miller". University of Utah School of Medicine.
  3. 1 2 "Lippard Lab". Lippard Lab.
  4. 1 2 "Craik Lab". University of California San Francisco.
  5. ↑ "Amy Barrios". scholar.google.com. Retrieved 2021-04-29.
  6. ↑ "Staff Q&A: Mark Karver, PhD, director of the Peptide Synthesis Core". Northwestern Medicine.
  7. ↑ "Method for monitoring intracellular tyrosine phosphatase activity". United States Patent and Trademark Office.
  8. ↑ The World Health Report 1998 (PDF). World Health Organization 1998.
  9. ↑ "Drug Found for Parasite that is Major Cause of Death Worldwide" (PDF). UC San Diego Health.
  10. ↑ Capparelli, Edmund V.; Bricker-Ford, Robin; Rogers, M. John; McKerrow, James H.; Reed, Sharon L. (27 December 2016). "Phase I Clinical Trial Results of Auranofin, a Novel Antiparasitic Agent". Antimicrobial Agents and Chemotherapy. 61 (1): e01947-16. doi: 10.1128/AAC.01947-16 . PMC   5192119 . PMID   27821451.
  11. ↑ Barrios, Amy. "Chemical Probes of Protein Tyrosine Phosphatase Activity". Grantome.
  12. ↑ "Pharm Sci Seminar - Dr. Amy Barrios". School of Pharmacy University of Wisconsin-Madison.
  13. ↑ "Previous Distinguished Mentor Recipients". The University of Utah.
  14. ↑ "MUSE Professors". MUSE.
  15. ↑ "2016 Presidential Scholars". @TheU.
  16. ↑ "Teva Pharmaceuticals Marc A. Goshko Memorial Grant Program Awardees 2015 - 2018". American Chemical Society.
  17. ↑ "Metals in Medicine". Gordon Research Conference.
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