John Riches

@richeslab.bsky.social

Clinical Reader and Consultant Haemato-oncologist at Barts Cancer Institute/Barts Hospital Specialist interest in chronic lymphocytic leukaemia and lymphoma with a particular focus on cancer and immuno-metabolism

This weeks recommended paper is by Samuel Witus and Michael Rapé +team who show that purine nucleotides stabilise the PPAT–NUDT5 complex to provide feedback control of purine biosynthesis, while thiopurines exploit the same interface with greater potency: www.nature.com/articles/s41...

Metabolite glues as a means of purine sensing and chemotherapeutic response - Nature

Purines can act as endogenous molecular glues in human cells by anchoring a rate-limiting enzyme in purine biosynthesis to its inhibitor, and modifying this mechanism could provide a way to improve th...

nature.com

This weeks recommended paper is by Samuel Witus and Michael Rapé +team who show that purine nucleotides stabilise the PPAT–NUDT5 complex to provide feedback control of purine biosynthesis, while thiopurines exploit the same interface with greater potency: www.nature.com/articles/s41...

Metabolite glues as a means of purine sensing and chemotherapeutic response - Nature

Purines can act as endogenous molecular glues in human cells by anchoring a rate-limiting enzyme in purine biosynthesis to its inhibitor, and modifying this mechanism could provide a way to improve th...

nature.com

This week my recommended read is by Ivan Montes, Hesham Sadek and team who show that mitochondria interact with nuclear pores via VDAC1–RANBP2. This contact fuels nuclear energetics, regulates gene expression, and is essential for cell differentiation. www.nature.com/articles/s41...

Mitochondria directly interact with the nuclear pore complex - Nature

Mitochondria interact directly with the nuclear pore complex via VDAC1–RANBP2 binding to sustain nuclear ATP levels.

nature.com

This week's recommended read is by Lennart Hoffmann, Tanja Maritzen and team who show that aldolase links metabolism to cell adhesion, with FBP acting as a signal to boost Rac1 activity to reorganize actin, enhance adhesion, and drive cell protrusion. www.nature.com/articles/s41...

Fructose-1,6-bisphosphate couples glycolytic activity to cell adhesion - Nature Cell Biology

Hoffmann et al. show that the glycolytic intermediate fructose-1,6-bisphosphate, which accumulates in the absence of aldolase, regulates focal adhesions by relieving RCC2-mediated Rac1 inhibition.

nature.com

This week's paper is by Anna Bång-Rudenstam and Mattias Belting and team who show a chondroitin sulfate–rich glycocalyx in glioblastoma blocks lipid uptake, protects from ferroptosis, and drives survival. Targeting this => lipid peroxidation & cell death. www.nature.com/articles/s41...

Tumour acidosis remodels the glycocalyx to control lipid scavenging and ferroptosis - Nature Cell Biology

Bång-Rudenstam et al. report that the acidic tumour microenvironment facilitates the assembly of chondroitin sulfate-enriched glycocalyx to disrupt lipid scavenging and prevent ferroptosis, thereby pr...

nature.com

This week's recommended paper is by Naiqi Wang and Di Yu and team who show that dietary PUFAs and MUFAs influence T cell lipid composition and resistance to ferroptosis, to regulate immune responses, with implications for vaccines and immunotherapies www.nature.com/articles/s41...

Lipid metabolism drives dietary effects on T cell ferroptosis and immunity - Nature

The susceptibility of mouse and human T cells to ferroptosis is determined by the balance of systemic polyunsaturated and monounsaturated fatty acids, highlighting a key role for lipid metabolism and ...

nature.com

This week's recommended read is by Amaia Zabala-Letona, Arkaitz Carracedo and team who have shown that polyamines (spermidine & spermine) regulate alternative splicing by binding to splicing factors to prevent the action of upstream kinases. Great work! www.nature.com/articles/s41...

Polyamine-dependent metabolic shielding regulates alternative splicing - Nature

Polyamines prevent the action of kinases on acidic phosphorylatable motifs in spliceosomal proteins, thus providing a mechanism for metabolite-mediated regulation of alternative splicing in cells.

nature.com

This week's paper is by Yajing Gao, Peter Tontonoz and team who show that the lipid transporter Aster-A limits excess accumulation of cholesterol in the membrane of Th17 cells dampening TCR-signalling to guard against excessive Th17-cell responses. www.science.org/doi/epdf/10....

T cell cholesterol transport links intestinal immune responses to dietary lipid absorption

The intrinsic pathways that control membrane organization in immune cells and their impact on cellular functions are poorly defined. We found that the nonvesicular cholesterol transporter Aster-A link...

science.org

This weeks paper is by Joey Li and Timothy O'Sullivan and team who show that while activated murine NK cells can perform de novo serine synthesis, human NKs can't - highlighting a species-specific sensitivity to environmental serine availability. www.nature.com/articles/s42...

Species-specific serine metabolism differentially controls natural killer cell functions - Nature Metabolism

Li et al. characterize overlapping and divergent metabolic requirements of human and murine NK cells in response to activation, with a focus on serine metabolism

nature.com

This week my paper of choice is by Faith Kaluba and Evan Lien and team who show that beta-hydroxybutyrate can be used by cancer cells to generate cytosolic acetyl-CoA via a non-canonical route that avoids oxidation in the mitochondria. Great work! doi.org/10.1038/s422...

An alternative route for β-hydroxybutyrate metabolism supports cytosolic acetyl-CoA synthesis in cancer cells - Nature Metabolism

Kaluba, Rogers et al. show that in cancer cells that can metabolize ketones, they may reroute them to produce cytosolic acetyl-CoA and support tumour growth.

doi.org