As promised, a 🧵 on our recent article now out in @NatureSMB! Co-led with @AbbyBartlett_ @Pagliarini_Lab @JudithSimcox, we find ACAD10/11 are NOT like other acyl-CoA dehydrogenases and instead catabolize atypical lipids called 4-hydroxy acids 🤯#lipidtime doi.org/10.1038/s41594-025-0…

So excited our paper on mitochondrial phosphatidylinositol (PI) is finally out and chosen as an Editor’s Highlight in @NatureComms! PI is a known component of mitochondrial membranes, yet how its levels within mitochondria shape core functions, is unknown. nature.com/articles/s41467-0…

PI is a prominent #mitochondrial lipid but little is known about its regulation and function. In work led by @Zak_Bakes and Rachel Guerra, we discovered that Fmp30p is a PI hydrolase that affects IM protein organization and CoQ production. #HHMInews #WashU nature.com/articles/s41467-0…

Inflammatory cytokines induce new cancer dependencies @NatureGenet @broadinstitute @MangusoLab nature.com/articles/s41588-0…

More good news in pancreatic cancer: Daraxonrasib recently doubled survival in metastatic disease in Phase 3. Now, combined with vopimetostat, it has shown a 92% objective response rate. This is far above the 25–35% seen with either drug alone. Thread below 👇

Pretty interesting story in @ScienceMagazine this week on what looks like a serious problem in the senescence field. More than 400 papers apparently used the wrong antibody for p16-INK4a — an antibody that actually recognizes a completely different, unrelated protein (a component of the actin cytoskeleton). This affects work on senescent cell accumulation in aging and disease, and most critically, some of the evidence base for senolytic drug research. What concerns me most is that many of these papers somehow got the "right" answer using the wrong antibody. That's not just an innocent reagent mix-up — it raises real questions about data fabrication or selective reporting in at least some of these labs. I've commented before about how ignoring data that doesn't fit the narrative is a major problem in certain areas of the longevity literature (e.g. sirtuins and NAD), and here a potentially widespread example in senescence. Hopefully journals will investigate and retract as necessary, but based on my experience that seems optimistic. One concrete fix is that journals should flag problematic antibody product codes at submission so reviewers can catch this before publication. Reviewers should absolutely be on the lookout for this going forward. However, these fixes won't address the larger problem. We need to understand how these scientists got the results they wanted and published them over 400 times (!!!): whether through intentional deception, incompetence, accident, or some legitimate explanation. Credit for discovering this goes to @addictedtoigno1 who wrote about it first on his blog: For Better Science science.org/content/article/…?

Excited (and a little relieved!) that our R13 for #KernLipidConference is officially funded by #NIH & #NIA 🎉 This year: lipid-centric mechanisms in #cardiometabolic & #neurodegenerative disease. Still time to register—see you in Breckenridge this August! kernconference.org/registrat…

We took ~750,000 whole genomes and found the putative mechanism by which mitochondrial DNA mutations accumulate with age in blood. Spoiler: we think these mutations arise by replication error and tag age-related clonal hematopoiesis. Read @Nature broad.io/ob2jft

Collaboration between our group and the Tirosh lab exploring a novel mTOR activator (they devloped) in combination with ixazomib for treatment of Acute Myeloid Leukemia! - link.springer.com/article/10…

📢NEW REVIEW: We introduce the distinction between essentiality and disproportionate essentiality when targeting OxPhos in cancer, and explain why this target does not support a therapeutic window once we consider the rest of the organism. portlandpress.com/biochemj/a…

In a paper just published in @sciencemagazine, we teamed up with @teichlab to construct the most detailed atlas to date of hormone production and action in humans at cellular resolution. (1/8) Link: science.org/doi/10.1126/scie…

New! Online now: Iron-addicted colorectal cancers exploit heme-complex II axis to resist oxidative cell death dlvr.it/TSlWK5

1/5 Cell identity is written in the proteome, not in the DNA, and not always in the RNA. Out on bioRxiv today: The first cell type-resolved, MS-based proteomic atlas of the human body. biorxiv.org/content/10.64898…

Delighted to share the final version of our story on mtDNA mutations and aging, published today. We show mtDNA mutation burden is a sensitive marker of somatic mosaicism (due to CHIP) in blood. Curious if this pattern will extens to solid organs, too. rdcu.be/fk4Ou

METLIN 960K is now integrated into the Mass Analytica MARS platform. Empirical MS/MS spectra from ~960,000 authentic standards. Not predicted. Not crowdsourced. Experimental data at scale. mass-analytica.com/products/… #Metabolomics #METLIN Publication: pubs.acs.org/doi/10.1021/acs…

@editasmed is also doing very exciting preclinical work with EDIT-401 by deleting the 3' UTR of LDLR, leading to 6-fold upregulation of the LDL receptor. They get 90% reduction of LDL-C, LPa, and ApoB in monkeys - the three major atherogenic lipoproteins VERVE-102 only gets 62% reduction of LDL-C...but of course this is human data. Editas IR says they will have first-in-human POC of their program by end of 2026. Stay tuned!

Just published @NEJM Marked and durable reduction of LDL cholesterol with one shot PCSK9 gene base editing @skathire nejm.org/doi/full/10.1056/NE…

Excited to share our new publication: "Exome-wide association study for blood lipids in 1,158,017 individuals from diverse populations." nature.com/articles/s41588-0… This study explores how multi-ancestry DNA sequencing has identified rare coding variants that influence blood lipids and atherosclerotic risk. Highlights include: • Discovery of rare coding variants across more than 1 million participants • Identification of novel lipid-associated genes • Insights into variant annotation and recessive associations • Potential therapeutic targets for coronary artery disease • The power of global biobank collaboration I extend my gratitude to all collaborators, participants, and consortium teams who made this research possible. I am proud to be part of this effort. Special thanks to my mentors, Drs. Yan Sun, Peter Wilson, @patrick_ellinor, and @pnatarajanmd, for their guidance and support throughout this work! For more details, see the previous thread: x.com/skoyamamd/status/18367…

This one is hard to see. The NIH Early Independence Award, one of the most competitive grants in the country for young scientists, will not go forward in FY2026. NIH says this is due to “administrative changes to funding opportunity processing and delays in approvals.”

Excited to share our new @biorxivpreprint from the @BradyLab & @PaulTitchenell lab on MASH, phosphatidylcholine metabolism, and copper biology with @JaclynE_x8 & biorxiv.org/content/10.64898…

Please share!!: If you know of any Afghan women/girls who were accepted to a university but couldn’t get a scholarship or find funding, please DM me. We’re working on a few things to approach this.