John Riches

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 ...

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...

Inhibiting macrophage-derived lactate transport restores cGAS–STING signalling and enhances antitumour immunity in glioblastoma - Nature Cell Biology Li, Cui, Yang, Lu, Jiang, Zhang and colleagues identify a lactate transport mechanism from tumour-associated macrophages that regulates DNA repair and immune cell infiltration, which could be targeted...

This week's paper is by Daqi Li and Xiuxing Wang and team who show that tumour associated macrophages supply glioblastoma stem cells with lactate to promote their proliferation and induce KU70 lactylation to block cGAS-STING signalling and remodel the TME. Great work! www.nature.com/articles/s41...

This week my recommended cancer metabolism paper is by Azusa Terasaki and Derick Okwan-Duodo and team who report that mitochondrial transfer from immune cells to cancer cells facilitates lymph node metastasis via the cGAS/STING immune evasion pathway. doi.org/10.1016/j.cm...

Driving discoveries for tomorrow's cancer care at Barts Cancer Institute YouTube video by BCIQMUL

Today, on #WorldCancerDay, we’re taking you behind the scenes at Queen Mary's Barts Cancer Institute and introducing you to the people who are making progress possible.

Follow us to stay up to date with new developments.

🧪 #UnitedByUnique #MedSky #OncoSky @qmul.bsky.social @cancerresearchuk.org

Hexokinase detachment from mitochondria drives the Warburg effect to support compartmentalized ATP production - Nature Metabolism Hexokinase detachment from the outer mitochondrial membrane is shown to support aerobic glycolysis in cancer cells. Differential localization of the HK1 isoform to the outer mitochondrial membrane, co...

This week's top paper is by Kimberley Huggler and Jason Cantor and team who show that hexokinase (HK) 2-dependence of cancer cells in HPLM is due to the subcellular distribution of HK1, with cytosolic HK supporting the Warburg effect. Great work! www.nature.com/articles/s42...

This week's recommended read is by Jian Gu and LIng Lu and team who show that tumour-derived ammonia drives Treg-specific enrichment. Tregs detoxify ammonia via the urea cycle and spermine synthesis, boosting Tregs to drive resistance. Great work! doi.org/10.1016/j.ce...

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.

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...

Happy New Year All! My first recommended read for 2026 is by Yaqui Wang, Thirumala-Devi Kanneganti and team who identify a new lytic cell death pathway, mitoxyperilysis, triggered by the synergy of innate immune activation and metabolic stress. Great work! doi.org/10.1016/j.ce...

So this week's recommended paper is not about cancer metabolism - but a study reporting the effects of space travel on human biology is always a great read! Well done to Jessica Pham, Catrina Jamieson and team! doi.org/10.1016/j.st...

Innate immune and metabolic signals induce mitochondria-dependent membrane lysis via mitoxyperiosis Wang et al. identify a new lytic cell death pathway, mitoxyperilysis, triggered by the synergy of innate immune activation and metabolic stress. This process is regulated by mTORC2 and involves persis...

This weeks highly recommended read is by Yaqiu Wang, Thirumala-Devi Kannaganti and colleagues who describe mitoxyperilysis - a distinct form of lytic cell death induced by innate immune signaling and metabolic disruption. www.cell.com/cell/fulltex...

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...

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....

Glucose restriction shapes pre-metastatic innate immune landscapes in the lung through exosomal TRAIL While targeting glucose metabolism shows potential in cancer therapy, its clinical implications remain unclear. This study finds that low-carbohydrate diets or impaired glucose metabolism in cancer ce...

This week's recommended read is by Cai-Yang Wu and Dong-Ming Kuang and team who show that despite suppressing primary tumour growth, glucose deprivation promotes lung metastasis by depleting natural killer cells via lung macrophages. Read more at:
www.cell.com/cell/fulltex...

Leucine inhibits degradation of outer mitochondrial membrane proteins to adapt mitochondrial respiration - Nature Cell Biology Li et al. uncover a connection between metabolic cues and mitochondrial protein degradation, showing that specifically leucine stabilizes outer mitochondrial membrane proteins by inhibiting ubiquityla...

This week's recommended metabolism read is by Qiaocho Li, Thorsten Hoppe and team who show that leucine suppresses degradation of outer mitochondrial membrane proteins to enhance respiration - defects in leucine catabolism promote lung cancer resistance. www.nature.com/articles/s41556-025-01799-3

My fav paper this week is by Akiko Ogawa and Fan-Yan Wei and team who report that toxic RNA catabolites are detoxified by the sequential action of ADK and ADAL - disruption of this pathway leads to AMPK inhibition and metabolic dysfunction. Great work! doi.org/10.1016/j.ce...

2025 British Society for Haematology Guideline for the treatment of chronic lymphocytic leukaemia Click on the article title to read more.

The 2025 British Society for Haematology Guideline for the treatment of CLL is out. A big thank you to everyone involved - particularly Renata and Piers! onlinelibrary.wiley.com/doi/10.1111/...

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

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...

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.

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...

Rewiring of cortical glucose metabolism fuels human brain cancer growth - Nature The cortex fuels essential physiological processes with glucose-derived carbon, while gliomas fuel their aggressiveness by rerouting glucose carbon pathways and scavenging alternative carbon sources s...

This week my recommended read is a great paper by Andrew Scott and Daniel Wahl and team who show that glioblastomas prioritise serine uptake to support nucleotide synthesis making them sensitive to dietary serine-glycine restriction: www.nature.com/articles/s41...

We're hiring! We're recruiting a post-doc to join my lab at Barts Cancer Institute in London investigating amino acid metabolism in lymphoma biology. Apply here: qmul-jobs.tal.net/vx/mobile-0/...

Structural basis for the dynamic regulation of mTORC1 by amino acids - Nature Using cryo-electron microscopy, the interactions of Sestrin2 and CASTOR1 with GATOR2 were resolved, revealing how mTORC1 activation is regulated and how nutrient availability triggers signalling for c...

This week my top (cancer) metabolism paper is by Max Valenstein and Kacper Rogala and colleagues who describe the structural basis for the regulation of mTORC1 by leucine and arginine. Outstanding work! doi.org/10.1038/s415...

Mitochondria protect against an intracellular pathogen by restricting access to folate As major consumers of cellular metabolites, mitochondria are poised to compete with invading microbes for the nutrients that they need to grow. Whether cells exploit mitochondrial metabolism to protec...

Mitochondria protect against an intracellular pathogen by restricting access to folate | Science www.science.org/doi/10.1126/...

d-cysteine impairs tumour growth by inhibiting cysteine desulfurase NFS1 - Nature Metabolism Zangari et al. show that d-cysteine targets NFS1, thus affecting Fe–S cluster biogenesis and impairing tumour growth.

d-cysteine impairs tumour growth by inhibiting cysteine desulfurase NFS1
www.nature.com/articles/s42...

Derepressing nuclear pyruvate dehydrogenase induces therapeutic cancer cell reprogramming Zhao et al. uncovered a nuclear-restricted acetyl-CoA regulatory mechanism where nucleus-localized pyruvate dehydrogenase complex (nPDC) is constitutively bound and repressed by nuclear protein ELMSAN...

This week's paper is some great work by Ting Zhoa and David Scadden who show that derepressing nuclear pyruvate dehydrogenase by blocking its interaction with the nuclear protein ELMSAN1 induces therapeutic cancer cell reprogramming: www.cell.com/cell-metabol...

Could a breath test detect blood cancer? - Barts Cancer Institute - Queen Mary University of London Molecules exhaled in the breath may provide clues to detect blood cancer, according to new research by scientists at Barts Cancer Institute. The findings could enable the development of a blood cancer...

Very pleased to report that the results of our blood cancer breath testing study have been published in @Hemasphere_EHA www.bci.qmul.ac.uk/general-news...
A massive thank you to everyone involved - particularly the patients and healthy volunteers!

Could a breath test detect blood cancer? - Barts Cancer Institute - Queen Mary University of London Molecules exhaled in the breath may provide clues to detect blood cancer, according to new research by scientists at Barts Cancer Institute. The findings could enable the development of a blood cancer...

📰Could a breath test detect blood cancer? New research from @richeslab.bsky.social ‬funded by @bartscharity.bsky.social suggests molecules exhaled in the breath might enable development of a simple, low-cost test to diagnose lymphoma.

@qmul.bsky.social @qmulfmd.bsky.social #medsky #oncosky 🧪

Macrophage respiratory complex III governs immune evasion : Immunometabolism th important implications for the pathophysiology of inflammatory diseases and cancer. A recent study by Zotta and colleagues provides new insights into the role of mitochondrial complex III (CIII) in...

Please have a look at our commentary on a recent cool paper from @lukeanthonyoneill.bsky.social lab:

journals.lww.com/immunometabo...

Cytidine diphosphate diacylglycerol synthase 2 is a synthetic lethal target in mesenchymal-like cancers - Nature Genetics The paralogs cytidine diphosphate diacylglycerol synthase 1 and 2 form a potentially targetable synthetic lethal relationship in mesenchymal-like cancers that involves disruption of lipid metabolism.

www.nature.com/articles/s41...

Cytidine diphosphate diacylglycerol synthase 2 is a synthetic lethal target in mesenchymal-like cancers

RIPK1 senses S-adenosylmethionine scarcity to drive cell death and inflammation How cells sense nutrients to maintain homeostasis and prevent cell death is a fundamental question. Chen et al. reveal that cells use RIPK1 to sense levels of the nutrient methionine and its metabolit...

This week's paper presents some intriguing observations by Hongbo Chen and Daichao Xu and team who show that the enzyme RIPK1 senses S-adenosylmethionine scarcity to drive cell death and inflammation. Great work! www.cell.com/cell-metabol...

Nerve-to-cancer transfer of mitochondria during cancer metastasis - Nature A study reports the development of a method to trace intercellular transfer of mitochondria, and demonstrates that cancer cells that receive mitochondria from neurons have enhanced metastatic capabili...

It was tough to decide this week as so many great cancer metabolism papers! But cancer-associated neurons transferring mitochondria to cancer cells to enhance their metastatic potential - wow! Super interesting observations by Gregory Hoover, Simon Grelet and team!: www.nature.com/articles/s41...

Metformin reduces the competitive advantage of Dnmt3aR878H HSPCs - Nature Dnmt3a mutations in mouse haematopoietic stem and progenitor cells equivalent to R882 mutations in human cause increased mitochondrial respiration, suggesting that this is a mechanism of clonal h...

This week its 2 papers demonstrating a link between mitochondrial metabolism and DNMT3A mutations in clonal haematopoiesis and potential for metformin: one by Malgorzata Gozdecka/George Vassiliou, the other by Mohsen Hosseini/Steven Chan: www.nature.com/articles/s41...
www.nature.com/articles/s41...