Excited to share our latest work revealing the requirements of pyrimidine nucleotides in the control of glucose oxidation and lipogenesis published in @ScienceMagazine. Huge congratulations to co-first authors Umakant Sahu and @VillaElodie!

We are delighted to celebrate the election of our esteemed colleague, Dr. Joe Bass, @JoeBass91471540 to the @theNAMedicine. This honor recognizes his outstanding contributions to the field of Endocrinology, Metabolism, and Molecular Medicine, and his pioneering research

Excited to share our new study out in @NatureCellBio! Led by postdoc @MikeLangePhD, we identify the first #LipidDroplet lipid quality control pathway: LD-localized FSP1 protects stored lipids from oxidative damage and prevents LD-initiated #ferroptosis. https://t.co/QBM8e07IlC

New in @MolecularCell! We discovered how mitochondrial succinate dehydrogenase (SDH) controls purine synthesis—and it's not what you'd expect. SDH loss → succinate buildup → SHMT2 succinylation → blocked one-carbon flow → no purines 🧬

Exciting to see other labs uncovering this emerging link between SDH activity and nucleotide synthesis, a conserved axis connecting mitochondrial metabolism to genome maintenance. @matthewhirschey @kcw00d @LabPuissant @LucasBSullivan

Together, these findings uncover a succinate–succinylation-SHMT2 axis linking mitochondrial metabolism to nucleotide synthesis. This connection provides new insight into how TCA cycle dysfunction reshapes cancer cell metabolism and opens doors for therapeutic targeting.

Cancer cells are resourceful; they activate the purine salvage pathway to compensate for impaired de novo synthesis. By combining SDH inhibition with antimetabolites blocking purine recycling, we achieved synergistic suppression of proliferation.

We hypothesized that this succinylation suppresses SHMT2 activity, limiting formate availability for purine synthesis. Indeed, supplementing cells with formate rescued de novo purine synthesis under SDH inhibition, confirming that one-carbon metabolism is the bottleneck.

In our case, SDH inhibition leads to succinate and succinyl-CoA accumulation, potentially driving protein succinylation that perturbs metabolism. We discovered that SHMT2, a key enzyme in mitochondrial one-carbon metabolism, becomes succinylated when SDH is inhibited.

This fits beautifully with prior work from the @hchristofk lab, showing that FH loss causes fumarate accumulation, inhibiting ADSL in the purine pathway.

Was this regulation unique to SDH? To find out, Mushtaq used CRISPR-Cas9 to knock out each TCA cycle enzyme and measured purine synthesis. Surprisingly, only SDHA and FH loss reduced purine synthesis. There’s something unique about SDH and FH in controlling purine metabolism.

Given this correlation, we examined whether SDH loss affects nucleotide synthesis using stable isotope tracing. Purine intermediates from 15N-glutamine decreased upon SDH loss or inhibition, while 15N-pyrimidine intermediates remained largely unaffected.

Using the FIREWORKS tool developed by the @MarcMendillo lab, Mushtaq found that expression of SDH subunits positively correlates with purine and pyrimidine synthesis genes. Knocking out SDHA, the catalytic subunit of SDH, caused a marked decrease in cell proliferation.

The TCA cycle doesn’t just power mitochondrial respiration through NADH/FADH2 production; its intermediates, like succinate, fumarate, and α-ketoglutarate, also act as signaling metabolites, influencing gene expression and cell fate.

Huge congratulations to first author @MushtaqNengroo and co-senior author @MarcMendillo for this fantastic collaboration, and to all our co-authors and colleagues!

Excited to share our latest work out today in @MolecularCell, revealing a molecular link between succinate dehydrogenase and purine synthesis, connecting two fundamental metabolic pathways. Congratulations to first author @MushtaqNengroo!

New preprint 🔥 showing that blocking JAK1/2 with ruxolitinib boosts food intake, preserves fat, and extends survival in lung cancer–associated cachexia. @eze_dantas https://t.co/n9FER7D3C9 #CancerMetabolism #Cachexia #LungCancer #JAKSTAT

Exciting postdoctoral opportunity in prostate cancer metabolism available in Nice, France! For more details or to apply, please contact Fred! 👇

Nice write-up on the work of ⁦@VamsiMootha⁩ and others using hypoxia (10-17% O2) to treat diseases and ameliorate the declines of aging. Harnessing Hypoxia | Harvard Medicine Magazine

🗽Save the date! March 24, 2026 Cancer Metabolism and Signaling Symposium @NYASciences co-organized by @LyssiotisLab @RichPossemato Speakers: @lab_manning @bensahralab @MarcusDGon @airdlab @KanarekNaama @JaviGBermudez @SantoshVardhana Josh R, Erika P +short talks from abstracts!