Peter Kreuzaler
@kreuzaler
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Incoming Junior PI @CECAD, with interest in #SpatialMetabolomics; #TME, and #immunometabolism. Always up for a chat.
Köln
Joined August 2016
JOB ALERT (9 days to go) We are looking for a computational postdoc to lead on the analysis of the NMGN Ageing Cluster spatial transcriptomics dataset. Start date: Flexible Tenure: 3 years Deadline: 28th Feb 2025 Informal queries welcome! Please RT
JOB ALERT We are seeking a Computational Research Assistant or Research Associate to help drive an ambitious multiomics ageing project part of the NMGN Mouse Ageing Cluster. https://t.co/l18v0LS1cJ
@MRCMouseNetwork @UnivCamPharm @SCICambridge
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Do you want to work with us as our scientific coordinator? Look no further! Apply here, we need you:
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Watch this space, my feeling is that this might not be the last you will hear about vitamins, spatial metabolomics and cancer.
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None of this would have been possible without the amazing support from the @CancerGrand, @TheCrick, Mariia Yuneva, the WHOLE team Rosetta, the data wizards Paolo Inglese and @avi_ghanate, the amazing STPs at the Crick and far too many to mention.🙏🙏🙏
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So there you have it, Myc increased SLC5A6 transcription, allowing more pantothenic acid influx and CoA synthesis. This fuels a biosynthetic metabolism required for efficient growth. This dependency can be exploited therapeutically by pantothenic acid withdrawal.
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In a reversal of events, overexpressing SLC5A6 alone was enough to increase tumour growths in otherwise Myc low cells. Who would have thought that a single vitamin is REQUIRED for efficient growth and SUFFICIENT for increased proliferation?
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Knock, knock. Who’s there? What’s the mechani….. We are scientists, of course we want to know the mechanism. To cut a very long story short, Myc can directly activate SLC5A6 transcription, the ONLY transporter for Pantothenic acid, and the floodgates are OPEN!
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Amazingly, the normally faster growing Myc high clones had lost all their proliferative advantage with the withdrawal of this one metabolite. 😮
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We next wanted to test, how much tumours require pantothenic acid for their growth. Well, quite a bit. A couple of months on a pantothenic acid free diet did not seem to harm the our animals, but breast cancer growth slowed significantly.👏
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A little sceptical, we wanted to see the differences in nutrient uptake CELL BY CELL. Back to our NanoSIMS workflow we could show that Myc high clones grow more avidly and incorporate more glucose and glutamine in the process.
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But does that mean their metabolism is quicker? Yes it does. We traced glucose and glutamine using DESI MSI, and Myc high clones show LESS lactate production and MORE Krebs cycle activity. Dr. Warburg, we need a word.🥸
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Slightly bedazzled, a quick search showed us that pantothenic acid is the precursor to make Coenzyme A. If the central carbon metabolism is our engine, CoA is the oil that keeps it running. Were we up to something?🧐
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A glance at our favourite energy drink showed us that PANtothenic acid is…everywhere….
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We developed a #DESI based MSI workflow and after A LOT of data crunching we found….pantothenic acid aka Vitamin B5, as the metabolite that is most significantly enriched in Myc high clones. Amazingly, this was true in human biopsies as well. 🤯
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We knew that tumours are heterogeneous. Some cells are more aggressive, some are less. But how does that affect metabolism? Let’s build a model and test it! We created a mammary tumor model, with two clones, one high in the oncogene MYC, one low for Myc.
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🚨Paper alert🚨 in #MSI and #tumormetabolism. Want to see metabolic tracing at single organelle resolution? Excited about spatial metabolic flux analysis? Want to know why your tumour likes an energy drink as much as your teenage children? Read on! https://t.co/whRNacvmWw
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Congratulations to Jan Rybniker, Alexander Simonis, and colleagues @UKKoeln - including Manuel Kock @BCCologne - for their exciting publication @CellCellPress entitled "Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa" https://t.co/tP9QU1cbKg
cell.com
Drug-resistant Pseudomonas aeruginosa poses an emerging threat to human health with an urgent need for alternative therapeutic approaches. Elucidation of the human immune response to the P. aerugin...
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We are seeking two #Postdoc talents to unravel the mysteries of #Metastasis #Dormancy and #ImmuneEvasion. Come join our @EMBO_YIP team and our collaborative programs on #BrainMetastasis
https://t.co/FA6OeL4CDd and #BoneMetastasis
https://t.co/6uic93FC5H plse DM & RT appreciated.
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