Nature Search

De novo pyrimidine biosynthesis inhibition synergizes with BCL-X_L targeting in pancreatic cancer

Pharmacologic inhibition of dihydroorotate dehydrogenase (DHODH) shows limited efficacy in pancreatic ductal adenocarcinoma (PDAC) models. Here the authors find that targeting the anti-apoptotic protein BCL-XL synergizes with DHODH inhibition in promoting apoptosis in PDAC cells, patient-derived organoids, and PDAC mouse models.

Huan Zhang
Naiara Santana-Codina
Joseph D. Mancias
ResearchOpen Access30 Jul 2025
Nature Communications

Volume: 16, P: 1-18
Compensatory metabolic networks in pancreatic cancers upon perturbation of glutamine metabolism

Glutaminase inhibition (GLSi) has promising activity against certain cancers. Here, the authors show that GLSi has no effect on multiple mouse models of pancreatic cancer and characterize the metabolic pathways activated in response to GLSi whose concomitant inhibition may have therapeutic utility.

Douglas E. Biancur
Joao A. Paulo
Alec C. Kimmelman
ResearchOpen Access03 Jul 2017
Nature Communications

Volume: 8, P: 1-15
Structural basis for the intracellular regulation of ferritin degradation

Ferritin, the cellular iron storage complex, binds NCOA4 and is trafficked to the lysosome for degradation and iron release. Here, authors present the cryo-EM structure of the NCOA4-Ferritin complex with biophysical and cellular characterization.

Fabian Hoelzgen
Thuy T. P. Nguyen
Gabriel A. Frank
ResearchOpen Access07 May 2024
Nature Communications

Volume: 15, P: 1-10
Discovery of a selective inhibitor of doublecortin like kinase 1

A highly selective inhibitor of the DCLK1/2 kinases is used to uncover the consequences of DCLK1 inhibition on viability, phosphosignaling and the transcriptome in patient-derived organoid models of pancreatic ductal adenocarcinoma.

Fleur M. Ferguson
Behnam Nabet
Nathanael S. Gray
Research06 Apr 2020
Nature Chemical Biology

Volume: 16, P: 635-643
Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules

The dTAG system is used to rapidly deplete tagged target proteins in vitro and in vivo, but there are context- and protein-specific differences in its effectiveness. Here, the authors develop a second generation dTAG molecule that can degrade previously recalcitrant target proteins in cells and mice.

Behnam Nabet
Fleur M. Ferguson
Nathanael S. Gray
ResearchOpen Access18 Sept 2020
Nature Communications

Volume: 11, P: 1-8
Plasticity in binding confers selectivity in ligand-induced protein degradation

Selectivity of ligand-induced protein degradation and dimerization is conferred by plastic interprotein contacts. Computational protein–protein docking reveals the underlying interprotein contacts to inform the design of a BRD4 selective degrader.

Radosław P. Nowak
Stephen L. DeAngelo
Eric S. Fischer
Research11 Jun 2018
Nature Chemical Biology

Volume: 14, P: 706-714
Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I

Inhibition of the autophagy–lysosome system upregulates surface expression of MHC class I proteins and enhances antigen presentation, and evokes a potent anti-tumour immune response that is mediated by CD8⁺ T cells.

Keisuke Yamamoto
Anthony Venida
Alec C. Kimmelman
Research22 Apr 2020
Nature

Volume: 581, P: 100-105
Reimagining high-throughput profiling of reactive cysteines for cell-based screening of large electrophile libraries

An improved workflow enables a 42-fold higher throughput of activity-based protein profiling.

Miljan Kuljanin
Dylan C. Mitchell
Steven P. Gygi
Research04 Jan 2021
Nature Biotechnology

Volume: 39, P: 630-641
Mutations in RABL3 alter KRAS prenylation and are associated with hereditary pancreatic cancer

A mutation in RAS oncogene family-like 3 (RABL3) is discovered in a family with multiple cases of pancreatic cancer. Zebrafish modeling and biochemical approaches suggest that truncated RABL3 elevates KRAS activity via accelerated prenylation.

Sahar Nissim
Ignaty Leshchiner
Wolfram Goessling
Research12 Aug 2019
Nature Genetics

Volume: 51, P: 1308-1314
Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy

Through a quantitative proteomics analysis, a cohort of proteins is identified that associate with autophagosomes, among them a new cargo receptor called NCOA4 that, in response to iron deprivation, targets ferritin to autophagosomes and thereby releases iron.

Joseph D. Mancias
Xiaoxu Wang
Alec C. Kimmelman
Research30 Mar 2014
Nature

Volume: 509, P: 105-109
The phenotypic spectrum of Schaaf-Yang syndrome: 18 new affected individuals from 14 families

Michael D. Fountain
Emmelien Aten
Christian P. Schaaf
Research19 May 2016
Genetics in Medicine

Volume: 19, P: 45-52

Search

De novo pyrimidine biosynthesis inhibition synergizes with BCL-X_L targeting in pancreatic cancer

Compensatory metabolic networks in pancreatic cancers upon perturbation of glutamine metabolism

Structural basis for the intracellular regulation of ferritin degradation

Discovery of a selective inhibitor of doublecortin like kinase 1

Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules

Plasticity in binding confers selectivity in ligand-induced protein degradation

Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I

Reimagining high-throughput profiling of reactive cysteines for cell-based screening of large electrophile libraries

Mutations in RABL3 alter KRAS prenylation and are associated with hereditary pancreatic cancer

Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy

The phenotypic spectrum of Schaaf-Yang syndrome: 18 new affected individuals from 14 families

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