Thank you so much for the kind words and all your excellent feedback!

We welcome all feedback and hope you enjoy the paper! /end

Many other nuggets in the paper that couldn't have been done without my brilliant co-author Angela, the support of @lydiafinley.bsky.social and the lab (@juliabrunner.bsky.social, @katrinaparas.bsky.social and more) and a superb editorial process @naturemetabolism.bsky.social. 7/

In ESCs, we think pyruvate uptake is especially important in the uterine environment, which has a different nutrient composition (low glucose, high lactate) than plasma or tissue culture media. For more on how NAD+ regeneration is coordinated in other cell types, stay tuned! 6/

Pyruvate uptake by naive ESCs requires but is not limited by transporter (MCT1) levels. Rather, mitochondrial pyruvate oxidation creates a metabolic gradient that dictates the strength and direction of pyruvate transport. These are some of my favorite experiments in the paper! 5/

Using embryonic stem cells (ESCs) as a model where cell state is intertwined with TCA cycle dynamics, we show that avid pyruvate uptake from the extracellular environment by naive ESCs is required for NAD+ regeneration in the setting of mitochondrial pyruvate oxidation. 4/

Any pyruvate that is captured in the mitochondria comes at the expense of NAD+ regeneration in the cytosol by LDH; moreover, the conversion of glucose to pyruvate itself requires NAD+. How do cells that burn glucose-derived pyruvate efficiently regenerate their cytosolic NAD+? 3/

Across mammalian cell metabolism, pyruvate entry into the TCA cycle is a tightly regulated metabolic node. While TCA cycle oxidation is critical for cellular anabolism, it has important metabolic costs, specifically for cytosolic redox balance. 2/

I'm excited to share our latest story from the
@lydiafinley.bsky.social lab, where we show that it's not just whether cells take up nutrients that matters, but how and where those metabolites are used. Out now in @naturemetabolism.bsky.social: rdcu.be/ejFTs 1/

Thrilled that my thesis work in @lydiafinley.bsky.social's lab is out in the world! We found that methotrexate targets a specific metabolic vulnerability in a particularly aggressive form of pediatric rhabdomyosarcoma. Thank you to everyone who contributed to this project over the years!

Our latest preprint identifies (targetable!) metabolic programs intrinsic to different cancer cell states in rhabdomyosarcoma, out just in time for @katrinaparas.bsky.social's thesis defense tomorrow!

Thrilled that my first post here is this absolutely monumental work by @katrinaparas.bsky.social and the @lydiafinley.bsky.social lab. It’s been so much fun to watch this story develop; read it if you have any interest in cell state, pediatric cancer, or of course metabolism!