UNDERSTANDING CELL SIGNALLING AS A BASIS FOR NEW THERAPEUTICS

Translating the biology of B common receptor- engaging cytokines into clinical medicine

Harshita Pant, Timothy R Hercus, Damon J Tumes, Kwok Ho Yip, Michael W Parker, Catherine M Owczarek, Angel F Lopez, David P Huston

2023-02-03

The family of cytokines that comprises IL-3, IL-5, and GM-CSF was discovered over 30 years ago, and their biological activities an..

Reaction hijacking of tyrosine tRNA synthetase as a new whole-of-life-cycle antimalarial strategy

Stanley C Xie, Riley D Metcalfe, Elyse Dunn, Craig J Morton, Shih-Chung Huang, Tanya Puhalovich, Yawei Du, Sergio Wittlin, Shuai Nie, Madeline R Luth, Liting Ma, Mi-Sook Kim, Charisse Flerida A Pasaje, Krittikorn Kumpornsin, Carlo Giannangelo, Fiona J Houghton, Alisje Churchyard, Mufuliat T Famodimu, Daniel C Barry, David L Gillett

2022-06-03

Aminoacyl transfer RNA (tRNA) synthetases (aaRSs) are attractive drug targets, and we present class I and II aaRSs as previously u..

Structural biology of cell surface receptors implicated in Alzheimer's disease.

Stefan J Hermans, Tracy L Nero, Craig J Morton, Jonathan H Gooi, Gabriela AN Crespi, Nancy C Hancock, Chen Gao, Kenta Ishii, Jasmina Markulić, Michael W Parker

2022-02-01

Alzheimer's disease is a common and devastating age-related disease with no effective disease-modifying treatments. Human genetics..

Messing with beta c: A unique receptor with many goals

Winnie L Kan, Karen S Cheung Tung Shing, Tracy L Nero, Timothy R Hercus, Denis Tvorogov, Michael W Parker, Angel F Lopez

2021-12-08

Our understanding of the biological role of the βc family of cytokines has evolved enormously since their initial identification a..

Structure of native HIV-1 cores and their interactions with IP6 and CypA

Tao Ni, Yanan Zhu, Zhengyi Yang, Chaoyi Xu, Yuriy Chaban, Tanya Nesterova, Jiying Ning, Till Bocking, Michael W Parker, Christina Monnie, Jinwoo Ahn, Juan R Perilla, Peijun Zhang

2021-11-01

The viral capsid plays essential roles in HIV replication and is a major platform engaging host factors. To overcome challenges in..

Design of proteasome inhibitors with oral efficacy in vivo against Plasmodium falciparum and selectivity over the human proteasome

Stanley C Xie, Riley D Metcalfe, Hirotake Mizutani, Tanya Puhalovich, Eric Hanssen, Craig J Morton, Yawei Du, Con Dogovski, Shih-Chung Huang, Jeffrey Ciavarri, Paul Hales, Robert J Griffin, Lawrence H Cohen, Bei-Ching Chuang, Sergio Wittlin, Ioanna Deni, Tomas Yeo, Kurt E Ward, Daniel C Barry, Boyin Liu

2021-09-28

The Plasmodium falciparum proteasome is a potential antimalarial drug target. We have identified a series of amino-amide boronates..

Development of [F-18]MIPS15692, a radiotracer with in vitro proof-of-concept for the imaging of MER tyrosine kinase (MERTK) in neuroinflammatory disease

Siu Wai Wong, Lucy Vivash, Ramesh Mudududdla, Nghi Nguyen, Stefan J Hermans, David M Shackleford, Judith Field, Lian Xue, Andrea Aprico, Nancy C Hancock, Mohammad Haskali, Michael A Stashko, Stephen Frye, Xiaodong Wang, Michele D Binder, Uwe Ackermann, Michael W Parker, Trevor J Kilpatrick, Jonathan B Baell

2021-09-23

MER tyrosine kinase (MERTK) upregulation is associated with M2 polarization of microglia, which plays a vital role in neuroregener..

Repurposing of drugs as STAT3 inhibitors for cancer therapy

Pathum S Thilakasiri, Rhynelle S Dmello, Tracy L Nero, Michael W Parker, Matthias Ernst, Ashwini L Chand

2021-02-02

Drug repurposing is a valuable approach in delivering new cancer therapeutics rapidly into the clinic. Existing safety and patient..

X-ray crystallography shines a light on pore-forming toxins

Bronte A Johnstone, Michelle P Christie, Craig J Morton, Michael W Parker

2021-01-01

A common form of cellular attack by pathogenic bacteria is to secrete pore-forming toxins (PFTs). Capable of forming transmembrane..

A Key Motif in the Cholesterol-Dependent Cytolysins Reveals a Large Family of Related Proteins

Jordan C Evans, Bronte A Johnstone, Sara L Lawrence, Craig J Morton, Michelle P Christie, Michael W Parker, Rodney K Tweten

2020-09-01

The cholesterol-dependent cytolysins (CDCs) are bacterial, β-barrel, pore-forming toxins. A central enigma of the pore-forming mec..

The structure of the extracellular domains of human interleukin 11? receptor reveals mechanisms of cytokine engagement

Riley D Metcalfe, Kaheina Aizel, Courtney O Zlatic, Paul M Nguyen, Craig J Morton, Daisy Sio-Seng Lio, Heung-Chin Cheng, Renwick CJ Dobson, Michael W Parker, Paul R Gooley, Tracy L Putoczki, Michael DW Griffin

2020-06-12

Interleukin (IL) 11 activates multiple intracellular signaling pathways by forming a complex with its cell surface α-receptor, IL-..

Monoubiquitination by the human Fanconi anemia core complex clamps FANCI: FANCD2 on DNA in filamentous arrays

Winnie Tan, Sylvie van Twest, Andrew Leis, Rohan Bythell-Douglas, Vincent J Murphy, Michael Sharp, Michael W Parker, Wayne Crismani, Andrew J Deans

2020-03-13

FANCI:FANCD2 monoubiquitination is a critical event for replication fork stabilization by the Fanconi anemia (FA) DNA repair pathw..

The structure of the PA28-20S proteasome complex from Plasmodium falciparum and implications for proteostasis

Stanley C Xie, Riley D Metcalfe, Eric Hanssen, Tuo Yang, David L Gillett, Andrew P Leis, Craig J Morton, Michael J Kuiper, Michael W Parker, Natalie J Spillman, Wilson Wong, Christopher Tsu, Lawrence R Dick, Michael DW Griffin, Leann Tilley

2019-11-01

The activity of the proteasome 20S catalytic core is regulated by protein complexes that bind to one or both ends. The PA28 regula..

An Intermolecular pi-Stacking Interaction Drives Conformational Changes Necessary to beta-Barrel Formation in a Pore-Forming Toxin

Joshua R Burns, Craig J Morton, Michael W Parker, Rodney K Tweten

2019-07-01

The crystal structures of the soluble monomers of the pore-forming cholesterol-dependent cytolysins (CDCs) contain two α-helical b..

EPO does not promote interaction between the erythropoietin and beta-common receptors (vol 8, 12457, 2018)

Karen S Cheung Tung Shing, Sophie E Broughton, Tracy L Nero, Kevin Gillinder, Melissa D Ilsley, Hayley Ramshaw, Angel F Lopez, Michael DW Griffin, Michael W Parker, Andrew C Perkins, Urmi Dhagat

2019-05-21

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been..

Repurposing the selective estrogen receptor modulator bazedoxifene to suppress gastrointestinal cancer growth.

Pathum Thilakasiri, Jennifer Huynh, Ashleigh R Poh, Chin Wee Tan, Tracy L Nero, Kelly Tran, Adam C Parslow, Shoukat Afshar-Sterle, David Baloyan, Natalie J Hannan, Michael Buchert, Andrew Mark Scott, Michael Dw Griffin, Frederic Hollande, Michael W Parker, Tracy L Putoczki, Matthias Ernst, Ashwini L Chand

2019-04-01

Excessive signaling through gp130, the shared receptor for the interleukin (IL)6 family of cytokines, is a common hallmark in soli..

Reaction mechanism of the bioluminescent protein mnemiopsin1 revealed by X-ray crystallography and QM/MM simulations

Maryam Molakarimi, Michael A Gorman, Ammar Mohseni, Zaiddodine Pashandi, Majid Taghdir, Hossein Naderi-Manesh, Reza H Sajedi, Michael W Parker

2019-01-04

Bioluminescence of a variety of marine organisms, mostly cnidarians and ctenophores, is carried out by Ca2+-dependent photoprotein..

Cholesterol-dependent cytolysins: from water-soluble state to membrane pore.

Michelle P Christie, Bronte A Johnstone, Rodney K Tweten, Michael W Parker, Craig J Morton

2018-10-01

The cholesterol-dependent cytolysins (CDCs) are a family of bacterial toxins that are important virulence factors for a number of ..

EPO does not promote interaction between the erythropoietin and beta-common receptors

Karen S Cheung Tung Shing, Sophie E Broughton, Tracy L Nero, Kevin Gillinder, Melissa D Ilsley, Hayley Ramshaw, Angel F Lopez, Michael DW Griffin, Michael W Parker, Andrew C Perkins, Urmi Dhagat

2018-08-20

A direct interaction between the erythropoietin (EPOR) and the beta-common (βc) receptors to form an Innate Repair Receptor (IRR) ..

The mechanism of GM-CSF inhibition by human GM-CSF auto-antibodies suggests novel therapeutic opportunities

Urmi Dhagat, Timothy R Hercus, Sophie E Broughton, Tracy L Nero, Karen S Cheung Tung Shing, Emma F Barry, Christy A Thomson, Steve Bryson, Emil F Pai, Barbara J McClure, John W Schrader, Angel F Lopez, Michael W Parker

2018-01-01

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor that can stimulate a variety of cells, ..