www.wehi.edu.au/people/isabelle-lucet My laboratory investigates how defects in signalling molecules called protein kinases cause major human diseases. In a normal cell, protein kinases control cell behaviour by regulating many fundamental processes within the cell.
But when protein kinases are out of control, normal cell development goes awry and can lead to cancers and inflammatory disorders.
We study the molecular structure of protein kinases to fully unravel their mechanism of action. We aim to identify new kinase-controlled regulatory pathways and develop novel therapeutic strategies for the treatment of blood cancers, inflammatory disorders and infectious diseases.
Find out more about Isabelle Lucet's experience
Isabelle Lucet's highlights
Isabelle Lucet's selected work
CHAPTER 13: A Structural Perspective of the Pseudokinome: Defining the Targetable Space
Displaying the 47 most recent scholarly works by Isabelle Lucet.
Mapping and functional analysis of heterochromatin protein 1 phosphorylation in the malaria parasite Plasmodium falciparum
Hai TN Bui, Igor Niederwieser, Megan J Bird, Weiwen Dai, Nicolas MB Brancucci, Suzette Moes, Paul Jenoe, Isabelle S Lucet, Christian Doerig, Till S Voss
Journal article | 2019 | Scientific Reports
Previous studies in model eukaryotes have demonstrated that phosphorylation of heterochromatin protein 1 (HP1) is important for dy..
The PEAK family of pseudokinases, their role in cell signalling and cancer
Onisha Patel, Michael J Roy, James M Murphy, Isabelle S Lucet
Journal article | 2019 | The FEBS Journal
The study of pseudokinases has uncovered that catalysis-independent functions play a critical role in cell signalling regulation. ..
Viral MLKL Homologs Subvert Necroptotic Cell Death by Sequestering Cellular RIPK3
Emma J Petrie, Jarrod J Sandow, Wil IL Lehmann, Lung-Yu Liang, Diane Coursier, Samuel N Young, Wilhelmus JA Kersten, Cheree Fitzgibbon, Andre L Samson, Annette V Jacobsen, Kym N Lowes, Amanda E Au, Helene Jousset Sabroux, Najoua Lalaoui, Andrew I Webb, Guillaume Lessene, Gerard Manning, Isabelle S Lucet, James M Murphy
Journal article | 2019 | Cell Reports
Conformational switching of the pseudokinase domain promotes human MLKL tetramerization and cell death by necroptosis
Emma J Petrie, Jarrod J Sandowl, Annette Jacobsen, Brian J Smith, Michael DW Griffin, Isabelle S Lucet, Weiwen Dai, Samuel N Young, Maria C Tanzer, Ahmad Wardak, Lung-Yu Liang, Angus D Cowan, Joanne M Hildebrand, Wilhelmus JA Kersten, Guillaume Lessene, John Silke, Peter E Czabotar, Andrew Webb, James M Murphy
Journal article | 2018 | Nature Communications
Structure of SgK223 pseudokinase reveals novel mechanisms of homotypic and heterotypic association
Onisha Patel, Michael DW Griffin, Santosh Panjikar, Weiwen Dai, Xiuquan Ma, Howard Chan, Celine Zheng, Ashleigh Kropp, James M Murphy, Roger J Daly, Isabelle S Lucet
Journal article | 2017 | Nature Communications
Homo- and Heterotypic Association Regulates Signaling by the SgK269/PEAK1 and SgK223 Pseudokinases
Ling Liu, Yu Wei Phua, Rachel S Lee, Xiuquan Ma, Yiping Jenkins, Karel Novy, Emily S Humphrey, Howard Chan, Robert Shearer, Poh Chee Ong, Weiwen Dai, Darren N Saunders, Isabelle S Lucet, Roger J Daly
Journal article | 2016 | Journal of Biological Chemistry
Hierarchical phosphorylation of apical membrane antigen 1 is required for efficient red blood cell invasion by malaria parasites
Boris Prinz, Katherine L Harvey, Louisa Wilcke, Ulrike Ruch, Klemens Engelberg, Laura Biller, Isabelle Lucet, Steffen Erkelenz, Dorothee Heincke, Tobias Spielmann, Christian Doerig, Conrad Kunick, Brendan S Crabb, Paul R Gilson, Tim W Gilberger
Journal article | 2016 | Scientific Reports
Biochemical and Structural Insights into Doublecortin-like Kinase Domain 1
Onisha Patel, Weiwen Dai, Mareike Mentzel, Michael DW Griffin, Juliette Serindoux, Yoann Gay, Stefanie Fischer, Shoukat Sterle, Ashleigh Kropp, Christopher J Burns, Matthias Ernst, Michael Buchert, Isabelle S Lucet
Journal article | 2016 | Structure
Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond.
Wesley C Van Voorhis, John H Adams, Roberto Adelfio, Vida Ahyong, Myles H Akabas, Pietro Alano, Aintzane Alday, Yesmalie Alemán Resto, Aishah Alsibaee, Ainhoa Alzualde, Katherine T Andrews, Simon V Avery, Vicky M Avery, Lawrence Ayong, Mark Baker, Stephen Baker, Choukri Ben Mamoun, Sangeeta Bhatia, Quentin Bickle, Lotfi Bounaadja, et al.
Journal article | 2016 | PLOS Pathogens
A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. M..
HSP90 activity is required for MLKL oligomerisation and membrane translocation and the induction of necroptotic cell death
AV Jacobsen, KN Lowes, MC Tanzer, IS Lucet, JM Hildebrand, EJ Petrie, MF van Delft, Z Liu, SA Conos, J-G Zhang, DCS Huang, J Silke, G Lessene, JM Murphy
Journal article | 2016 | Cell Death & Disease
Plasmodium falciparum Adhesins Play an Essential Role in Signalling and Activation of Invasion into Human Erythrocytes
Wai-Hong Tham, Nicholas TY Lim, Greta E Weiss, Sash Lopaticki, Brendan RE Ansell, Megan Bird, Isabelle Lucet, Dominique Dorin-Semblat, Christian Doerig, Paul R Gilson, Brendan S Crabb, Alan F Cowman
Journal article | 2015 | PLOS Pathogens
Genome-wide binding and mechanistic analyses of Smchd1-mediated epigenetic regulation
Kelan Chen, Jiang Hu, Darcy L Moore, Ruijie Liu, Sarah A Kessans, Kelsey Breslin, Isabelle S Lucet, Andrew Keniry, Huei San Leong, Clare L Parish, Douglas J Hilton, Richard JLF Lemmers, Silvere M van der Maarel, Peter E Czabotar, Renwick CJ Dobson, Matthew E Ritchie, Graham F Kay, James M Murphy, Marnie E Blewitt
Journal article | 2015 | Proceedings of the National Academy of Sciences
An Extensive Antigenic Footprint Underpins Immunodominant TCR Adaptability against a Hypervariable Viral Determinant
Usha K Nivarthi, Stephanie Gras, Lars Kjer-Nielsen, Richard Berry, Isabelle S Lucet, John J Miles, Samantha L Tracy, Anthony W Purcell, David S Bowden, Margaret Hellard, Jamie Rossjohn, James McCluskey, Mandvi Bharadwaj
Journal article | 2014 | The Journal of Immunology
Activation of the pseudokinase MLKL unleashes the four-helix bundle domain to induce membrane localization and necroptotic cell death
Joanne M Hildebrand, Maria C Tanzer, Isabelle S Lucet, Samuel N Young, Sukhdeep K Spall, Pooja Sharma, Catia Pierotti, Jean-Marc Garnier, Renwick CJ Dobson, Andrew I Webb, Anne Tripaydonis, Jeffrey J Babon, Mark D Mulcair, Martin J Scanlon, Warren S Alexander, Andrew F Wilks, Peter E Czabotar, Guillaume Lessene, James M Murphy, John Silke
Journal article | 2014 | Proceedings of the National Academy of Sciences
An exported kinase (FIKK4.2) that mediates virulence-associated changes in Plasmodium falciparum-infected red blood cells
Lev M Kats, Kate M Fernandez, Fiona K Glenister, Susann Herrmann, Donna W Buckingham, Ghizal Siddiqui, Laveena Sharma, Rebecca Bamert, Isabelle Lucet, Micheline Guillotte, Odile Mercereau-Puijalon, Brian M Cooke
Journal article | 2014 | International Journal for Parasitology
The Pseudokinase MLKL Mediates Necroptosis via a Molecular Switch Mechanism
James M Murphy, Peter E Czabotar, Joanne M Hildebrand, Isabelle S Lucet, Jian-Guo Zhang, Silvia Alvarez-Diaz, Rowena Lewis, Najoua Lalaoui, Donald Metcalf, Andrew I Webb, Samuel N Young, Leila N Varghese, Gillian M Tannahill, Esme C Hatchell, Ian J Majewski, Toru Okamoto, Renwick CJ Dobson, Douglas J Hilton, Jeffrey J Babon, Nicos A Nicola, et al.
Journal article | 2013 | Immunity
Plasmodium kinases as targets for new-generation antimalarials.
Isabelle S Lucet, Andrew Tobin, David Drewry, Andrew F Wilks, Christian Doerig
Journal article | 2012 | Future Medicinal Chemistry
There is an urgent need for the development of new antimalarial drugs with novel modes of actions. The malarial parasite, Plasmodi..
Differential Recognition of CD1d-alpha-Galactosyl Ceramide by the V beta 8.2 and V beta 7 Semi-invariant NKT T Cell Receptors
Daniel G Pellicci, Onisha Patel, Lars Kjer-Nielsen, Siew Siew Pang, Lucy C Sullivan, Konstantinos Kyparissoudis, Andrew G Brooks, Hugh H Reid, Stephanie Gras, Isabelle S Lucet, Ruide Koh, Mark J Smyth, Thierry Mallevaey, Jennifer L Matsuda, Laurent Gapin, James McCluskey, Dale I Godfrey, Jamie Rossjohn
Journal article | 2009 | Immunity
Dissecting specificity in the Janus kinases: the structures of JAK-specific inhibitors complexed to the JAK1 and JAK2 protein tyrosine kinase domains.
Neal K Williams, Rebecca S Bamert, Onisha Patel, Christina Wang, Patricia M Walden, Andrew F Wilks, Emmanuelle Fantino, Jamie Rossjohn, Isabelle S Lucet
Journal article | 2009 | Journal of Molecular Biology
The Janus kinases (JAKs) are a pivotal family of protein tyrosine kinases (PTKs) that play prominent roles in numerous cytokine si..
Crystal structures of the Lyn protein tyrosine kinase domain in its Apo- and inhibitor-bound state.
Neal K Williams, Isabelle S Lucet, S Peter Klinken, Evan Ingley, Jamie Rossjohn
Journal article | 2009 | Journal of Biological Chemistry
The Src-family protein-tyrosine kinase (PTK) Lyn is the most important Src-family kinase in B cells, having both inhibitory and st..
The 2.7 A crystal structure of the autoinhibited human c-Fms kinase domain.
Mark Walter, Isabelle S Lucet, Onisha Patel, Sophie E Broughton, Rebecca Bamert, Neal K Williams, Emmanuelle Fantino, Andrew F Wilks, Jamie Rossjohn
Journal article | 2007 | Journal of Molecular Biology
c-Fms, a member of the Platelet-derived Growth Factor (PDGF) receptor family of receptor tyrosine kinases (RTKs), is the receptor ..
Hijacking of a substrate-binding protein scaffold for use in mycobacterial cell wall biosynthesis.
Zara Marland, Travis Beddoe, Leyla Zaker-Tabrizi, Isabelle S Lucet, Rajini Brammananth, James C Whisstock, Matthew CJ Wilce, Ross L Coppel, Paul K Crellin, Jamie Rossjohn
Journal article | 2006 | Journal of Molecular Biology
The waxy cell wall is crucial to the survival of mycobacteria within the infected host. The cell wall is a complex structure rich ..
Two distinct regions of the large serine recombinase TnpX are required for DNA binding and biological function.
Vicki Adams, Isabelle S Lucet, Fleur E Tynan, Martina Chiarezza, Pauline M Howarth, Jonathan Kim, Jamie Rossjohn, Dena Lyras, Julian I Rood
Journal article | 2006 | Molecular Microbiology
The large serine recombinase, TnpX, from the Clostridium perfringens integrative mobilizable element Tn4451, consists of three dom..
The structural basis of Janus kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor.
Isabelle S Lucet, Emmanuelle Fantino, Michelle Styles, Rebecca Bamert, Onisha Patel, Sophie E Broughton, Mark Walter, Christopher J Burns, Herbert Treutlein, Andrew F Wilks, Jamie Rossjohn
Journal article | 2006 | Blood
JAK2, a member of the Janus kinase (JAK) family of protein tyrosine kinases (PTKs), is an important intracellular mediator of cyto..
Identification of the structural and functional domains of the large serine recombinase TnpX from Clostridium perfringens.
Isabelle S Lucet, Fleur E Tynan, Vicki Adams, Jamie Rossjohn, Dena Lyras, Julian I Rood
Journal article | 2005 | Journal of Biological Chemistry
Members of the large serine resolvase family of site-specific recombinases are responsible for the movement of several mobile gene..
DNA binding properties of TnpX indicate that different synapses are formed in the excision and integration of the Tn4451 family.
Vicki Adams, Isabelle S Lucet, Dena Lyras, Julian I Rood
Journal article | 2004 | Molecular Microbiology
Site-specific recombination is an important mechanism for genetic exchange. Insertional recombination mediated by the recently del..
The large resolvase TnpX is the only transposon-encoded protein required for transposition of the Tn4451/3 family of integrative mobilizable elements.
Dena Lyras, Vicki Adams, Isabelle Lucet, Julian I Rood
Journal article | 2004 | Molecular Microbiology
Chloramphenicol resistance in Clostridium perfringens and Clostridium difficile is often encoded by catP genes located within the ..
The FxRxHrS motif: a conserved region essential for DNA binding of the VirR response regulator from Clostridium perfringens.
Sheena McGowan, Isabelle S Lucet, Jackie K Cheung, Milena M Awad, James C Whisstock, Julian I Rood
Journal article | 2002 | Journal of Molecular Biology
The VirSR two-component signal transduction pathway regulates virulence and toxin production in Clostridium perfringens, the causa..
Cytological and biochemical characterization of the FtsA cell division protein of Bacillus subtilis.
A Feucht, I Lucet, MD Yudkin, J Errington
Journal article | 2001 | Molecular Microbiology
The actin-like protein FtsA is present in many eubacteria, and genetic experiments have shown that it plays an important, sometime..
Fate of the SpoIIAB*-ADP liberated after SpoIIAB phosphorylates SpoIIAA of Bacillus subtilis.
CS Lee, I Lucet, MD Yudkin
Journal article | 2000 | Journal of Bacteriology
Phosphorylation of SpoIIAA catalyzed by SpoIIAB helps to regulate the first sporulation-specific sigma factor, sigma(F), of Bacill..
Direct interaction between the cell division protein FtsZ and the cell differentiation protein SpoIIE.
I Lucet, A Feucht, MD Yudkin, J Errington
Journal article | 2000 | The EMBO Journal
SpoIIE is a bifunctional protein with two critical roles in the establishment of cell fate in Bacillus subtilis. First, SpoIIE is ..
Genotype, phenotype, and protein structure in a regulator of sporulation: effects of mutations in the spoIIAA gene of Bacillus subtilis.
D Barillà, I Lucet, A Kuhlmann, MD Yudkin
Journal article | 1999 | Journal of Bacteriology
SpoIIAA, a phosphorylatable protein, is essential to the regulation of sigmaF, the first sporulation-specific transcription factor..
The Bacillus subtilis regulator protein SpoIIE shares functional and structural similarities with eukaryotic protein phosphatases 2C.
R Schroeter, S Schlisio, I Lucet, M Yudkin, R Borriss
Journal article | 1999 | FEMS Microbiology Letters
Dephosphorylation of SpoIIAA-P by SpoIIE is strictly dependent on the presence of the bivalent metal ions Mn2+ or Mg2+. Replacemen..
Purification, kinetic properties, and intracellular concentration of SpoIIE, an integral membrane protein that regulates sporulation in Bacillus subtilis.
I Lucet, R Borriss, MD Yudkin
Journal article | 1999 | Journal of Bacteriology
SpoIIE is a bifunctional protein which controls sigmaF activation and formation of the asymmetric septum in sporulating Bacillus s..