Search

Your search keyword '"Garner, Amanda L."' showing total 390 results
Start Over Author "Garner, Amanda L."
390 results on '"Garner, Amanda L."'

1. MNK-driven eIF4E phosphorylation regulates the fibrogenic transformation of mesenchymal cells and chronic lung allograft dysfunction

Author

Walker, Natalie M., Ibuki, Yuta, McLinden, A. Patrick, Misumi, Keizo, Mitchell, Dylan C., Kleer, Gabriel G., Lock, Alison M., Vittal, Ragini, Sonenberg, Nahum, Garner, Amanda L., and Lama, Vibha N.

Subjects
Cell Signaling Technologies, Transplantation of organs, tissues, etc. -- Health aspects, Medical research -- Health aspects, Medicine, Experimental -- Health aspects, Genetic translation -- Health aspects, Stem cells -- Health aspects, Biotechnology industry -- Health aspects, Health care industry
Abstract

Tissue fibrosis remains unamenable to meaningful therapeutic interventions and is the primary cause of chronic graft failure after organ transplantation. Eukaryotic translation initiation factor (eIF4E), a key translational regulator, serves as convergent target of multiple upstream profibrotic signaling pathways that contribute to mesenchymal cell (MC) activation. Here, we investigate the role of MAP kinase-interacting serine/threonine kinase-induced (MNK-induced) direct phosphorylation of eIF4E at serine 209 (Ser209) in maintaining fibrotic transformation of MCs and determine the contribution of the MNK/ eIF4E pathway to the pathogenesis of chronic lung allograft dysfunction (CLAD). MCs from patients with CLAD demonstrated constitutively higher eIF4E phosphorylation at Ser209, and eIF4E phospho-Ser209 was found to be critical in regulating key fibrogenic protein autotaxin, leading to sustained p-catenin activation and profibrotic functions of CLAD MCs. MNK1 signaling was upregulated in CLAD MCs, and genetic or pharmacologic targeting of MNK1 activity inhibited eIF4E phospho- Ser209 and profibrotic functions of CLAD MCs in vitro. Treatment with an MNK1/2 inhibitor (eFT-508) abrogated allograft fibrosis in an orthotopic murine lung-transplant model. Together these studies identify what we believe is a previously unrecognized MNK/ eIF4E/ATX/[beta]-catenin signaling pathway of fibrotic transformation of MCs and present the first evidence, to our knowledge, for the utility of MNK inhibitors in fibrosis., Introduction Lung transplantation has the worst long-term prognosis among all solid-organ transplantations, with a 10-year survival of only 20% (1). The major cause of these poor long-term outcomes is progressive [...]

Published
2024
Full Text
View/download PDF

2. Approaches for the Discovery of Small Molecule Ligands Targeting microRNAs

Author

Lorenz, Daniel A., Garner, Amanda L., Bernstein, Peter R., Series editor, Georg, Gunda I., Series editor, Keller, Thomas, Series editor, Kobayashi, Toshi, Series editor, Lowe, John A., Series editor, Meanwell, Nicholas A., Series editor, Saxena, Anil Kumar, Series editor, Stilz, Ulrich, Series editor, Supuran, Claudiu T., Series editor, Zhang, Ao, Series editor, and Garner, Amanda L., editor

Published
2018
Full Text
View/download PDF

5. Empowering Voices: Inspiring Women in Medicinal Chemistry.

Author

Blanco, Maria-Jesus, Bronson, Joanne J., DiMauro, Erin F., Dzierba, Carolyn, Eggen, MariJean, Garner, Amanda L., Georg, Gunda, Giarolla, Jeanine, Goodwin, Nicole C., Grenier-Davies, Melissa C., Haskell-Luevano, Carrie, Holzgrabe, Ulrike, Huang, Rong, Lagiakos, H. Rachel, Leftheris, Katerina, Martin, Yvonne, Matos, Maria João, May-Dracka, Tricia L., Müller, Christa E., and Newman, Amy H.

Published
2024
Full Text
View/download PDF

13. Live cell screening to identify RNA-binding small molecule inhibitors of the pre-let-7–Lin28 RNA–protein interactionElectronic supplementary information (ESI) available: Material and methods, RiPCA HTS protocol, other assay protocols, supplemental figures and tables. See DOI: https://doi.org/10.1039/d4md00123k

Author

Rosenblum, Sydney L., Soueid, Dalia M., Giambasu, George, Vander Roest, Steve, Pasternak, Alexander, DiMauro, Erin F., Simov, Vladimir, and Garner, Amanda L.

Abstract

Dysregulation of the networking of RNA-binding proteins (RBPs) and RNAs drives many human diseases, including cancers, and the targeting of RNA–protein interactions (RPIs) has emerged as an exciting area of RNA-targeted drug discovery. Accordingly, methods that enable the discovery of cell-active small molecule modulators of RPIs are needed to propel this emerging field forward. Herein, we describe the application of live-cell assay technology, RNA interaction with protein-mediated complementation assay (RiPCA), for high-throughput screening to identify small molecule inhibitors of the pre-let-7d–Lin28A RPI. Utilizing a combination of RNA-biased small molecules and virtual screening hits, we discovered an RNA-binding small molecule that can disrupt the pre-let-7–Lin28 interaction demonstrating the potential of RiPCA for advancing RPI-targeted drug discovery.

Published
2024
Full Text
View/download PDF

15. Enhancing the Visibility of Women in the ACS Division of Medicinal Chemistry (ACS MEDI)

Author

Aldrich, Jane, primary, Allen, Shelley, additional, Araujo, Erika, additional, Bronson, Joanne, additional, Bryant-Friedrich, Amanda, additional, Cyr, Shana K., additional, DiMauro, Erin F., additional, Dzierba, Carolyn, additional, Garner, Amanda L., additional, Georg, Gunda I., additional, Goodwin, Nicole C., additional, Haranahalli, Krupanandan, additional, Huang, Rong, additional, Leftheris, Katerina, additional, May-Dracka, Tricia L., additional, Olson, Margaret E., additional, and Blanco, Maria-Jesus, additional

Published
2023
Full Text
View/download PDF

18. MINCR is not a MYC-induced lncRNA

Author

Hart, Jonathan R., Weinberg, Marc S., Morris, Kevin V., Roberts, Thomas C., Janda, Kim D., Garner, Amanda L., and Vogt, Peter K.

Published
2016

21. Inhibitor of MYC identified in a Kröhnke pyridine library

Author

Hart, Jonathan R., Garner, Amanda L., Yu, Jing, Ito, Yoshihiro, Sun, Minghao, Ueno, Lynn, Rhee, Jin-Kyu, Baksh, Michael M., Stefan, Eduard, Hartl, Markus, Bister, Klaus, Vogt, Peter K., and Janda, Kim D.

Published
2014

24. A live-cell assay for the detection of pre-microRNA–protein interactions† †Electronic supplementary information (ESI) available: General methods and materials, assay protocols, and supplemental figures. See DOI: 10.1039/d0cb00055h

Author

Rosenblum, Sydney L., Lorenz, Daniel A., and Garner, Amanda L.

Subjects
Chemistry
Abstract

Leveraging bioorthogonal chemistry- and split-luciferase assay technologies, we have devised a new assay for the live-cell detection of RNA–protein interactions, RNA interaction with Protein-mediated Complementation Assay or RiPCA., Recent efforts in genome-wide sequencing and proteomics have revealed the fundamental roles that RNA-binding proteins (RBPs) play in the life cycle and function of coding and non-coding RNAs. While these methodologies provide a systems-level view of the networking of RNA and proteins, approaches to enable the cellular validation of discovered interactions are lacking. Leveraging the power of bioorthogonal chemistry- and split-luciferase-based assay technologies, we have devised a conceptually new assay for the live-cell detection of RNA–protein interactions (RPIs), RNA interaction with Protein-mediated Complementation Assay, or RiPCA. As proof-of-concept, we utilized the interaction of the pre-microRNA, pre-let-7, with its binding partner, Lin28. Using this system, we have demonstrated the selective detection of the pre-let-7-Lin28 RPI in both the cytoplasm and nucleus. Furthermore, we determined that this technology can be used to discern relative affinities for specific sequences as well as of individual RNA binding domains. Thus, RiPCA has the potential to serve as a useful tool in supporting the investigation of cellular RPIs.

Published
2020

25. RiPCA: An Assay for the Detection of RNA‐Protein Interactions in Live Cells

Author

Rosenblum, Sydney L. and Garner, Amanda L.

Subjects
Medical Laboratory Technology, General Immunology and Microbiology, General Neuroscience, RNA, RNA-Binding Proteins, Biological Assay, Health Informatics, General Pharmacology, Toxicology and Pharmaceutics, Luciferases, Article, General Biochemistry, Genetics and Molecular Biology
Abstract

Increasing interest in studying and modulating the interactions between RNAs and their RNA-binding proteins (RBPs) has borne the need for enabling technologies. Existing means of detecting RNA-protein interactions (RPIs) are often limited to biochemical or post-lysis methods or cell-based methods that require the addition of an RNA-based affinity tag, such as the MS2 hairpin, precluding them from use in detecting small or highly processed RNAs. Taking advantage of bioorthogonal chemistry- and split-luciferase-based technologies, we developed an assay for the detection of RPIs in live cells. This article details the protocol and design considerations for RiPCA, RNA interaction with Protein-mediated Complementation Assay. Basic Protocol 1: Design and optimization of a cellular assay for the detection of RNA-protein interactions

Published
2022

29. Discovery of Surfactins as Inhibitors of MicroRNA Processing Using Cat-ELCCA

Author

Robertson, Andrew W., primary, Sandoval, Jorge, additional, Mohamed, Osama G., additional, Zhuang, Yihao, additional, Gallagher, Erin E., additional, Schmidt, Jennifer, additional, Caratelli, Lisa, additional, Menon, Arya, additional, Schultz, Pamela J., additional, Torrez, Rachel M., additional, Hay, Catherine L., additional, Bell, Bailey A., additional, Price, Paul A., additional, Garner, Amanda L., additional, and Tripathi, Ashootosh, additional

Published
2021
Full Text
View/download PDF

41. Cyclin‐dependent kinase 4 inhibits the translational repressor 4E‐BP1 to promote cap‐dependent translation during mitosis–G1 transition.

Author

Mitchell, Dylan C., Menon, Arya, and Garner, Amanda L.

Subjects
GENETIC translation, CELL cycle regulation, TRANSLATIONS, PROTEIN synthesis, OCCUPATIONAL roles
Abstract

Phosphorylation of translational repressor eukaryotic translation initiation factor 4E (eIF4E)‐binding protein 1 (4E‐BP1) controls the initiation of cap‐dependent translation, a type of protein synthesis that is frequently upregulated in human diseases such as cancer. Because of its critical cellular function, it is not surprising that multiple kinases can post‐translationally modify 4E‐BP1 to drive aberrant cap‐dependent translation. We recently reported a site‐selective chemoproteomic method for uncovering kinase–substrate interactions, and using this approach, we discovered the cyclin‐dependent kinase (CDK)4 as a new 4E‐BP1 kinase. Herein, we describe our extension of this work and reveal the role of CDK4 in modulating 4E‐BP1 activity in the transition from mitosis to G1, thereby demonstrating a novel role for this kinase in cell cycle regulation. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

46. Enhancement of a catalysis-based fluorometric detection method for palladium through rational fine-tuning of the palladium species

Author

Garner, Amanda L., Fengling Song, and Koide, Kazunori

Subjects
Allylic compounds -- Structure, Allylic compounds -- Chemical properties, Catalysis -- Analysis, Coordination compounds -- Structure, Coordination compounds -- Chemical properties, Oxidation-reduction reaction -- Analysis, Palladium -- Chemical properties, Palladium -- Optical properties, Chemistry
Abstract

The improvement of the catalysis-based fluorescent probe for palladium is described by rationally fine-tuning the redox and coordination chemistries of the palladium species involved in the O-deallylation reaction. The studies have shown palladium detection in various active pharmaceutical ingredients, spent catalytic converter materials and a metal scavenger resin.

Published
2009

47. Oxidation state-specific fluorescent method for palladium(II) and platinum(IV) based on the catalyzed aromatic Claisen rearrangement

Author

Garner, Amanda L. and Koide, Kazunori

Subjects
Oxidation-reduction reaction -- Analysis, Palladium -- Chemical properties, Palladium -- Optical properties, Platinum -- Chemical properties, Platinum -- Optical properties, Chemistry
Abstract

The fluorogenic probe is used for detecting [Pd.sup.II/IV] and [Pt.sup.IV] via Claisen rearrangement to fluorescent green-yellow compound even in functionalized compounds and [Pt.sup.0]-water, each without sample preparation steps. This method can also be used in the pharmaceutical industry, the environment, and Pd/Pt quality control.

Published
2008

48. A highly sensitive fluorescent sensor for palladium based on the allylic oxidative insertion mechanism

Author

Song, Fengling, Garner, Amanda L., and Koide, Kazunori

Subjects
Palladium -- Optical properties, Chemical detectors -- Usage, Fluorescein -- Optical properties, Chemistry
Abstract

The development of a new fluorescent sensor for detecting palladium (Pd) based on the allylic oxidative insertion mechanism is described. The sensor is highly sensitive and robust and hence can be used in pharmaceutical and mining industries.

Published
2007

Catalog

Books, media, physical & digital resources
See catalog results