Associate Professor @ Fred Hutch
Studying metabolic constraints of cancer cell proliferation
https://research.fredhutch.org/sullivan/en.html
On a mote of dust suspended in a sunbeam
Lucas Sullivan
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Also, check out this excellent N&V writeup from @frezzalab.bsky.social that nicely summarizes our findings and contextualizes them with other fascinating work on succinate interactions with nucleotide synthesis from the @bensahralab.bsky.social and Hirschey Labs!
www.nature.com/articles/s42...
Nature Metabolism, Published online: 08 May 2026; doi:10.1038/s42255-026-01532-wMetabolomic analysis of plasma from metformin-treated humans, together with mechanistic studies in mouse models, reveals that metformin selectively inhibits mitochondrial complex I in the intestinal epithelium. This mechanism unifies multiple clinical effects of metformin, including enhanced intestinal glucose use, improved postprandial glycaemic control and increased production of GDF15 and N-lactoyl-phenylalanine.
Very interesting articles about cancer metabolism this month, and insightful reviews.
Highlighting fresh articles and comments about cysteine and glutathione from @lucasbsullivan.bsky.social @ginadenicola.bsky.social @harrislab.bsky.social and others
metabolist.wordpress.com/2026/05/04/m...
Nature Metabolism
This paper greatly expands our earlier preprint findings, including:
Enzyme assays demonstrating competitive inhibition of human ATCase activity by succinate.
Demonstrating impaired pyrimidine synthesis in a mouse model of SDHB deficient pituitary tumors.
And much more!
New out this week in @natmetabolism.nature.com – We measured dynamic aspartate changes following mitochondrial inhibition, finding that SDH inhibition causes a counterintuitive "aspartate rebound" effect, mediated by succinate impairing pyrimidine synthesis.
www.nature.com/articles/s42...
Our review dissecting the nuanced roles of mitochondria during cancer progression, was just published in @annualreviews.bsky.social. This one was written by David Sokolov with his approachable and entertaining writing style. Check it out:
www.annualreviews.org/content/jour...
Cell metabolism is a dynamic network of highly interconnected biochemical reactions. In this issue of Nature Metabolism, time-lapse analysis of the amino acid aspartate revealed an unexpected regulati...
Many thanks to the team, including first authors @madelouhart.bsky.social and David Sokolov, and to @davidmacphersonlab.bsky.social for a huge assist with mouse modeling. Also thanks to @jeannakhle.bsky.social
for shepherding this story through the publication process and to NIGMS/NCI for funding.
Cristina Muñoz Pinedo
🚨Excited to announce a new preprint from our lab, where we describe an ancient metabolic axis that controls mitochondrial genome copy number; a mechanism we uncovered in human cells that stretches through evolution to control mtDNA in flies, yeast and even plants!
Lucas Sullivan
Lucas Sullivan
Lucas Sullivan
Very happy to share our new paper. Together with our wonderful collaborators, we found that L-2-HG, a metabolite often viewed as “toxic,” also has an essential physiological function in mice. www.nature.com/articles/s41...
l-2-Hydroxyglutarate is identified as a legitimate physiological signalling metabolite, and control of its levels is essential for postnatal growth and survival and correct renal development and funct...
Cystine / Glutathione / NADPH SLC33A1 exports oxidized glutathione to maintain endoplasmic reticulum redox homeostasis Shanshan Liu (刘珊珊), Mark Gad, Caifan Li (李采蘩), Kevin Cho, Yuyang Liu (刘雨洋),…
