NOVEL CHEMICAL TOOLS TO STUDY CATHEPSIN X ACTIVATION

Grant number: DE180100418 | Funding period: 2018 - 2023

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Abstract

This project aims to develop new chemical tools that can measure the specific activation of cathepsin X in cells, tissues, and live animals, as well as specific inhibitors for cathepsin X. The cysteine protease cathepsin X mediates basic biological functions that are essential for life, including cell communication, phagocytosis, immune maturation and neuritogenesis. The outcomes should benefit the wider research community. They could have long-term implications for health and disease, and deliver economic benefits through commercialisation of the novel tools.

Related publications (14)

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Protease-activated receptors in health and disease.

Chloe J Peach, Laura E Edgington-Mitchell, Nigel W Bunnett, Brian L Schmidt

2023-01-01

Proteases are signaling molecules that specifically control cellular functions by cleaving protease-activated receptors (PARs). Th..

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Ubiquitin-like protein 3 (UBL3) is required for MARCH ubiquitination of major histocompatibility complex class II and CD86

Haiyin Liu, Kayla R Wilson, Ashley M Firth, Christophe Macri, Patrick Schriek, Annabelle B Blum, Javiera Villar, Samuel Wormald, Mitch Shambrook, Bangyan Xu, Hui Jing Lim, Hamish EG McWilliam, Andrew F Hill, Laura E Edgington-Mitchell, Irina Caminschi, Mireille H Lahoud, Elodie Segura, Marco J Herold, Jose A Villadangos, Justine D Mintern

2022-04-11

The MARCH E3 ubiquitin (Ub) ligase MARCH1 regulates trafficking of major histocompatibility complex class II (MHC II) and CD86, mo..

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MHC Class II Ubiquitination Regulates Dendritic Cell Function and Immunity

Kayla R Wilson, Devi Jenika, Annabelle B Blum, Christophe Macri, Bangyan Xu, Haiyin Liu, Patrick Schriek, Dominik Schienstock, Lauren Francis, F Victor Makota, Satoshi Ishido, Scott N Mueller, Mireille H Lahoud, Irina Caminschi, Laura E Edgington-Mitchell, Jose A Villadangos, Justine D Mintern

2021-11-01

MHC class II (MHC II) Ag presentation by dendritic cells (DCs) is critical for CD4+ T cell immunity. Cell surface levels of MHC II..

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Cathepsin S Evokes PAR(2)-Dependent Pain in Oral Squamous Cell Carcinoma Patients and Preclinical Mouse Models

Huu Tu Nguyen, Kenji Inoue, Elyssa Chen, Bethany M Anderson, Caroline M Sawicki, Nicole N Scheff, Hung D Tran, Dong H Kim, Robel G Alemu, Lei Yang, John C Dolan, Cheng Z Liu, Malvin N Janal, Rocco Latorre, Dane D Jensen, Nigel W Bunnett, Laura E Edgington-Mitchell, Brian L Schmidt

2021-09-01

Oral squamous cell carcinoma (SCC) pain is more prevalent and severe than pain generated by any other form of cancer. We previousl..

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Legumain Induces Oral Cancer Pain by Biased Agonism of Protease-Activated Receptor-2

Nguyen Huu Tu, Dane D Jensen, Bethany M Anderson, Elyssa Chen, Nestor N Jimenez-Vargas, Nicole N Scheff, Kenji Inoue, Hung D Tran, John C Dolan, Tamaryn A Meek, Morley D Hollenberg, Cheng Z Liu, Stephen J Vanner, Malvin N Janal, Nigel W Bunnett, Laura E Edgington-Mitchell, Brian L Schmidt

2021-01-06

Oral squamous cell carcinoma (OSCC) is one of the most painful cancers, which interferes with orofacial function including talking..

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System-wide biochemical analysis reveals ozonide antimalarials initially act by disruptingPlasmodium falciparumhaemoglobin digestion

Carlo Giannangelo, Ghizal Siddiqui, Amanda De Paoli, Bethany M Anderson, Laura E Edgington-Mitchell, Susan A Charman, Darren J Creek

2020-06-01

Ozonide antimalarials, OZ277 (arterolane) and OZ439 (artefenomel), are synthetic peroxide-based antimalarials with potent activity..

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Lysosomal degradation products induce Coxiella burnetii virulence

Patrice Newton, David R Thomas, Shawna CO Reed, Nicole Lau, Bangyan Xu, Sze Ying Ong, Shivani Pasricha, Piyush B Madhamshettiwar, Laura E Edgington-Mitchell, Kaylene J Simpson, Craig R Roy, Hayley J Newton

2020-03-24

Coxiella burnetii is an intracellular pathogen that replicates in a lysosome-like vacuole through activation of a Dot/Icm-type IVB..

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Application of a Sulfoxonium Ylide Electrophile to Generate Cathepsin X-Selective Activity-Based Probes

Simon J Mountford, Bethany M Anderson, Bangyan Xu, Elean S Tay, Monika Szabo, Hoang My-Linh, Jiayin Diao, Luigi Aurelio, Rhiannon Campden, Erik Lindstrom, Erica K Sloan, Robin M Yates, Nigel W Bunnett, Philip E Thompson, Laura E Edgington-Mitchell

2020-03-20

Cathepsin X/Z/P is cysteine cathepsin with unique carboxypeptidase activity. Its expression is associated with cancer and neurodeg..

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High-Resolution Confocal Fluorescence Imaging of Serine Hydrolase Activity in Cryosections - Application to Glioma Brain Unveils Activity Hotspots Originating from Tumor-Associated Neutrophils

Niina Aaltonen, Prosanta K Singha, Hermina Jakupovic, Thomas Wirth, Haritha Samaranayake, Sanna Pasonen-Seppanen, Kirsi Rilla, Markku Varjosalo, Laura E Edgington-Mitchell, Paulina Kasperkiewicz, Marcin Drag, Sara Kalvala, Eemeli Moisio, Juha R Savinainen, Jarmo T Laitinen

2020-03-15

BACKGROUND: Serine hydrolases (SHs) are a functionally diverse family of enzymes playing pivotal roles in health and disease and h..

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Proteomics and Imaging in Crohn's Disease: TAILS of Unlikely Allies

Barbara Mainoli, Simon Hirota, Laura E Edgington-Mitchell, Cathy Lu, Antoine Dufour

2020-02-01

Crohn's disease (CD) is a chronic relapsing inflammatory bowel disease (IBD) that may be marked by debilitating symptoms of abdomi..

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N-Terminomics/TAILS Profiling of Macrophages after Chemical Inhibition of Legumain

Bethany M Anderson, Luiz GN de Almeida, Henna Sekhon, Daniel Young, Antoine Dufour, Laura E Edgington-Mitchell

2020-01-28

Legumain (asparaginyl endopeptidase) is the only protease with a preference for cleavage after asparagine residues. Increased legu..

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Loss of O-Linked Protein Glycosylation in Burkholderia cenocepacia Impairs Biofilm Formation and Siderophore Activity and Alters Transcriptional Regulators

Cameron C Oppy, Leila Jebeli, Miku Kuba, Clare V Oates, Richard Strugnell, Laura E Edgington-Mitchell, Miguel A Valvano, Elizabeth L Hartland, Hayley J Newton, Nichollas E Scott

2019-11-01

O-linked protein glycosylation is a conserved feature of the Burkholderia genus. The addition of the trisaccharide β-Gal-(1,3)-α-G..

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N-Terminomics/TAILS Profiling of Proteases and Their Substrates in Ulcerative Colitis

Marilyn H Gordon, Anthonia Anowai, Daniel Young, Nabangshu Das, Rhiannon I Campden, Henna Sekhon, Zoe Myers, Barbara Mainoli, Sameeksha Chopra, Peter S Thuy-Boun, Jayachandran Kizhakkedathu, Gurmeet Bindra, Humberto B Jijon, Steven Heitman, Robin Yates, Dennis W Wolan, Laura E Edgington-Mitchell, Wallace K MacNaughton, Antoine Dufour

2019-11-01

Dysregulated protease activity is often implicated in the initiation of inflammation and immune cell recruitment in gastrointestin..

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Application of a chemical probe to detect neutrophil elastase activation during inflammatory bowel disease

Bethany M Anderson, Daniel P Poole, Luigi Aurelio, Garrett Z Ng, Markus Fleischmann, Paulina Kasperkiewicz, Celine Morissette, Marcin Drag, Ian R van Driel, Brian L Schmidt, Stephen J Vanner, Nigel W Bunnett, Laura E Edgington-Mitchell

2019-09-16

Neutrophil elastase is a serine protease that has been implicated in the pathogenesis of inflammatory bowel disease. Due to post-t..