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Discovery of a ZIP7 inhibitor from a Notch pathway screen

A cell-based phenotypic screen identifying inhibitors of Notch signaling led to the discovery of NVS-ZP7-4, which blocks the activity of the zinc transporter SLC39a7 (ZIP7) and induces cell death through an ER stress mechanism.

Erin Nolin
Sara Gans
Christy J. Fryer
Research14 Jan 2019
Nature Chemical Biology

Volume: 15, P: 179-188
Extracellular modulation of TREK-2 activity with nanobodies provides insight into the mechanisms of K2P channel regulation

K2P channels are important regulators of cellular electrical activity. Here the authors show how nanobody fragments can be used to detect and modulate TREK2 K2P channel activity to provide insight into the mechanism of gating.

Karin E. J. Rödström
Alexander Cloake
Stephen J. Tucker
ResearchOpen Access16 May 2024
Nature Communications

Volume: 15, P: 1-13
The structural basis of lipid scrambling and inactivation in the endoplasmic reticulum scramblase TMEM16K

TMEM16K is a member of the TMEM16 family of integral membrane proteins that are either lipid scramblases or chloride channels. Here the authors combine cell biology, electrophysiology measurements, X-ray crystallography, cryo-EM and MD simulations to structurally characterize TMEM16K and show that it is an ER-resident lipid scramblase.

Simon R. Bushell
Ashley C. W. Pike
Elisabeth P. Carpenter
ResearchOpen Access02 Sept 2019
Nature Communications

Volume: 10, P: 1-16
Structure and function of the SIT1 proline transporter in complex with the COVID-19 receptor ACE2

The SIT1-ACE2 complex transports the amino acid proline and is the receptor of SARS-CoV-2. Here, the authors identify specific sequence requirements for proline transport and explain for how a missense mutation causes iminoglycinuria.

Huanyu Z. Li
Ashley C. W. Pike
David B. Sauer
ResearchOpen Access29 Jun 2024
Nature Communications

Volume: 15, P: 1-11
The structural basis of fatty acid elongation by the ELOVL elongases

ELOVLs are membrane-embedded enzymes that elongate very long chain fatty acids, precursors of sphingolipids and ceramides. The first crystal structure of a human ELOVL reveals an unexpected reaction mechanism, suggesting potential approaches for inhibition in disease.

Laiyin Nie
Tomas C. Pascoa
Elisabeth P. Carpenter
Research10 Jun 2021
Nature Structural & Molecular Biology

Volume: 28, P: 512-520
The amino acid transporter SLC7A5 is required for efficient growth of KRAS-mutant colorectal cancer

Colorectal tumors with mutated KRAS and APC require the amino acid transporter SLC7A5 to drive tumorigenesis. Mechanistically, SLC7A5 drives transcriptional and metabolic reprogramming by maintaining intracellular amino acid levels, leading to enhanced protein synthesis.

Arafath K. Najumudeen
Fatih Ceteci
Owen J. Sansom
Research07 Jan 2021
Nature Genetics

Volume: 53, P: 16-26
Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis

Here the authors uncovered CNOT3, a subunit of the CCR4-NOT complex, as an essential modulator of translation in leukemia. The work pointed to the potential of targeting the posttranscriptional circuitry via CNOT3 as a therapeutic vulnerability in acute myeloid leukemia.

Maryam Ghashghaei
Yilin Liu
Ly P. Vu
ResearchOpen Access15 Mar 2024
Nature Communications

Volume: 15, P: 1-18
A systematic CRISPR screen defines mutational mechanisms underpinning signatures caused by replication errors and endogenous DNA damage

Nik-Zainal and colleagues leverage CRISPR–Cas9 and whole-genome sequencing to examine mutational patterns following knockout of 42 human DNA repair genes. They further develop and validate a clinically relevant tool to detect mismatch repair-deficient tumors.

Xueqing Zou
Gene Ching Chiek Koh
Serena Nik-Zainal
Research26 Apr 2021
Nature Cancer

Volume: 2, P: 643-657
Genome-wide discovery of somatic regulatory variants in diffuse large B-cell lymphoma

The driver mutations for the two main molecular subgroups of diffuse large B-cell lymphoma (DLBCL) are poorly defined. Here, an integrative genomics analysis identifies 3′ UTR NFKBIZ mutations within the activated B-cell DLBCL subgroup and small FCGR2B amplifications in the germinal centre B-cell DLBCL subgroup.

Sarah E. Arthur
Aixiang Jiang
Ryan D. Morin
ResearchOpen Access01 Oct 2018
Nature Communications

Volume: 9, P: 1-14
Metabolic profiling stratifies colorectal cancer and reveals adenosylhomocysteinase as a therapeutic target

In this study, Vande Voorde et al. investigate the potential of untargeted metabolomics as a stratification tool for colorectal cancer (CRC). They present a comprehensive pipeline to uncover metabolic vulnerabilities in CRC based on its genetic origin. With this approach, they show perturbations in methionine metabolism linked to APC deficiency, and identify adenosylhomocysteinase as an actionable therapeutic target.

Johan Vande Voorde
Rory T. Steven
Owen J. Sansom
ResearchOpen Access14 Aug 2023
Nature Metabolism

Volume: 5, P: 1303-1318
Degradation of eukaryotic polypeptide chain initiation factor (eIF) 4G in response to induction of apoptosis in human lymphoma cell lines

Michael J Clemens
Martin Bushell
Simon J Morley
Research07 Dec 1998
Oncogene

Volume: 17, P: 2921-2931
Targeted error-suppressed quantification of circulating tumor DNA using semi-degenerate barcoded adapters and biotinylated baits

Miguel Alcaide
Stephen Yu
Ryan D. Morin
ResearchOpen Access05 Sept 2017
Scientific Reports

Volume: 7, P: 1-19

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