• Publications
  • Influence
A SARS-CoV-2 Protein Interaction Map Reveals Targets for Drug-Repurposing
TLDR
A human–SARS-CoV-2 protein interaction map highlights cellular processes that are hijacked by the virus and that can be targeted by existing drugs, including inhibitors of mRNA translation and predicted regulators of the sigma receptors. Expand
IRE1 Signaling Affects Cell Fate During the Unfolded Protein Response
TLDR
There is a causal link between the duration of UPR branch signaling and life or death cell fate after ER stress, and key findings from studies in cell culture were recapitulated in photoreceptors expressing mutant rhodopsin in animal models of retinitis pigmentosa. Expand
Active-Site Inhibitors of mTOR Target Rapamycin-Resistant Outputs of mTORC1 and mTORC2
TLDR
This work uses two novel and specific mTOR kinase domain inhibitors (PP242 and PP30) to show that pharmacological inhibition of mTOR blocks the phosphorylation of Akt at S473 and prevents its full activation, and shows that the TORKinib PP242 is a more effective mTORC1 inhibitor than rapamycin. Expand
RAF inhibitors transactivate RAF dimers and ERK signaling in cells with wild-type BRAF
TLDR
Because RAF inhibitors do not inhibit ERK signalling in other cells, the model predicts that they would have a higher therapeutic index and greater antitumour activity than mitogen-activated protein kinase (MEK) inhibitors, but could also cause toxicity due to MEK/ERK activation. Expand
Targets of the cyclin-dependent kinase Cdk1
TLDR
The identities of these substrates reveal that Cdk1 employs a global regulatory strategy involving phosphorylation of other regulatory molecules as well as phosphorylated of the molecular machines that drive cell-cycle events. Expand
Escape from HER family tyrosine kinase inhibitor therapy by the kinase inactive HER3
TLDR
The experimental abrogation of HER3 resistance by small interfering RNA knockdown restores potent pro-apoptotic activity to otherwise cytostatic HER TKIs, re-affirming the oncogene-addicted nature of HER2-driven tumours and the therapeutic promise of this oncoprotein target. Expand
A Pharmacological Map of the PI3-K Family Defines a Role for p110α in Insulin Signaling
TLDR
It is found that p110alpha is the primary insulin-responsive PI3-K in cultured cells, whereas p110beta is dispensable but sets a phenotypic threshold for p110 alpha activity, which illustrates systematic target validation using a matrix of inhibitors that span a protein family. Expand
The translational landscape of mTOR signalling steers cancer initiation and metastasis
TLDR
A clinically relevant ATP site inhibitor of mTOR, INK128, is developed, which reprograms this gene expression signature with therapeutic benefit for prostate cancer metastasis, for which there is presently no cure. Expand
A chemical switch for inhibitor-sensitive alleles of any protein kinase
TLDR
A chemical genetic strategy for sensitizing protein kinases to cell-permeable molecules that do not inhibit wild-type kinases is described, allowing for rapid functional characterization of members of this important gene family. Expand
Control of landmark events in meiosis by the CDK Cdc28 and the meiosis-specific kinase Ime2.
TLDR
It is speculated that several unique features of the meiotic cell division reflect a division of labor and regulatory coordination between Ime2 and Cdc28, which have critical roles in meiotic S phase and M phase. Expand
...
1
2
3
4
5
...