L
Leila N. Varghese
Researcher at Ludwig Institute for Cancer Research
Publications - 20
Citations - 2451
Leila N. Varghese is an academic researcher from Ludwig Institute for Cancer Research. The author has contributed to research in topics: Janus kinase & Cytokine receptor. The author has an hindex of 13, co-authored 20 publications receiving 1914 citations. Previous affiliations of Leila N. Varghese include Walter and Eliza Hall Institute of Medical Research & Université catholique de Louvain.
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Journal ArticleDOI
The Pseudokinase MLKL Mediates Necroptosis via a Molecular Switch Mechanism
James M. Murphy,Peter E. Czabotar,Peter E. Czabotar,Joanne M Hildebrand,Joanne M Hildebrand,Isabelle S Lucet,Jian-Guo Zhang,Jian-Guo Zhang,Silvia Alvarez-Diaz,Silvia Alvarez-Diaz,Rowena S. Lewis,Rowena S. Lewis,Najoua Lalaoui,Najoua Lalaoui,Donald Metcalf,Donald Metcalf,Andrew I. Webb,Andrew I. Webb,Samuel N. Young,Samuel N. Young,Leila N. Varghese,Leila N. Varghese,Gillian M. Tannahill,Gillian M. Tannahill,Esme C. Hatchell,Esme C. Hatchell,Ian J. Majewski,Ian J. Majewski,Toru Okamoto,Toru Okamoto,Renwick C. J. Dobson,Renwick C. J. Dobson,Douglas J. Hilton,Douglas J. Hilton,Jeffrey J. Babon,Jeffrey J. Babon,Nicos A. Nicola,Nicos A. Nicola,Andreas Strasser,Andreas Strasser,John Silke,John Silke,Warren S. Alexander,Warren S. Alexander +43 more
TL;DR: Structural-guided mutation of the MLKL pseudoactive site resulted in constitutive, RIPK3-independent necroptosis, demonstrating that modification ofMLKL is essential for propagation of the ne croptosis pathway downstream of RIPK 3.
Journal ArticleDOI
A robust methodology to subclassify pseudokinases based on their nucleotide-binding properties.
James M. Murphy,James M. Murphy,Qingwei Zhang,Samuel N. Young,Michael L. Reese,Fiona P. Bailey,Patrick A. Eyers,Daniela Ungureanu,Henrik Hammaren,Olli Silvennoinen,Leila N. Varghese,Leila N. Varghese,Kelan Chen,Kelan Chen,Anne Tripaydonis,Natalia Jura,Koichi Fukuda,Jun Qin,Zachary L. Nimchuk,Mary Beth Mudgett,Sabine Elowe,Christine L. Gee,Ling Liu,Roger J. Daly,Gerard Manning,Jeffrey J. Babon,Jeffrey J. Babon,Isabelle S Lucet +27 more
TL;DR: The thermal-shift assay is proposed to be adopted as the standard technique for establishing the nucleotide-binding and catalytic potential of kinase-like domains.
Journal ArticleDOI
Suppression of Cytokine Signaling by SOCS3: Characterization of the Mode of Inhibition and the Basis of Its Specificity
Jeffrey J. Babon,Nadia J. Kershaw,Nadia J. Kershaw,James M. Murphy,James M. Murphy,Leila N. Varghese,Leila N. Varghese,Artem Laktyushin,Samuel N. Young,Isabelle S Lucet,Raymond S. Norton,Raymond S. Norton,Nicos A. Nicola,Nicos A. Nicola +13 more
TL;DR: Surprisingly, it is found that SOCS3 simultaneously bound JAK and the cytokine receptor to which it is attached, revealing how specificity is generated in SOCS action and explaining why SOCS 3 inhibits only a subset of cytokines.
Journal ArticleDOI
The molecular regulation of Janus kinase (JAK) activation.
Jeffrey J. Babon,Jeffrey J. Babon,Isabelle S Lucet,Isabelle S Lucet,James M. Murphy,James M. Murphy,Nicos A. Nicola,Nicos A. Nicola,Leila N. Varghese,Leila N. Varghese +9 more
TL;DR: The JAK (Janus kinase) family members serve essential roles as the intracellular signalling effectors of cytokine receptors, and the current knowledge of their physiological functions and the causative role of activating and inactivating JAK mutations in human diseases is reviewed.
Journal ArticleDOI
SOCS3 binds specific receptor–JAK complexes to control cytokine signaling by direct kinase inhibition
Nadia J. Kershaw,James M. Murphy,James M. Murphy,Nicholas P. D. Liau,Nicholas P. D. Liau,Leila N. Varghese,Leila N. Varghese,Artem Laktyushin,Eden L Whitlock,Isabelle S Lucet,Nicos A. Nicola,Nicos A. Nicola,Jeffrey J. Babon,Jeffrey J. Babon +13 more
TL;DR: In this article, the crystal structure of SOCS3 bound to JAK2 and a fragment of the interleulkin-6 receptor reveals how it exerts its inhibitory activity by blocking substrate binding.