Lyssiotis Lab

Rewiring of cortical glucose metabolism fuels human brain cancer growth - Nature The cortex fuels essential physiological processes with glucose-derived carbon, while gliomas fuel their aggressiveness by rerouting glucose carbon pathways and scavenging alternative carbon sources such as environmental amino acids, providing a potential therapeutic target.

#NatMetabPicks | In @nature.com led by @danwahlmd.bsky.social‬ @lyssiotislab.bsky.social @dnagrathlab.bsky.social WN Al-Holou ( @umich.edu )

Gliomas take up serine from the tumor microenvironment, and can be targeted with dietary serine restriction.

🧪

www.nature.com/articles/s41...

🔗 Check out the full preprint for details & beautiful figures:
www.biorxiv.org/content/10.1...

👏 Congrats to Narges and teams!
🙏 To our awesome collaborators!
cc: @UMPhysiology

10/ Key message
Aspartate aminotransferases (GOT1 & GOT2) are essential for red cell development—primarily through their link to chromatin modification (epigenetic regulation), not just metabolism or aspartate pools!

9/ Human cell relevance
In primary human blood progenitors, knocking out GOT1/2 also blocked RBC formation & increased cell death, mirroring mouse results.

8/ Clue: Epigenetics! 🧬
GOT1/2 deletion caused abnormal chromatin histone methylation in erythroid cells, suggesting an epigenetic block to development. Loss of GOT1/2 activates apoptosis & cell cycle arrest genes.

7/ Bringing in a tissue-specific, LbNOX mouse model, we then demonstrated that correcting NADH reductive stress didn’t rescue the anemia. So MAS/redox was not the mechanism!

6/ Is it about redox? 🔴⚫
GOT1/2 are part of the malate-aspartate shuttle (MAS), which balances NAD+ and NADH. But deleting another MAS enzyme, MDH1, didn't cause anemia. 🤔

5/ Got1 vs. Got2
Surprisingly, Got1 or Got2 loss both caused anemia, but altered aspartate in opposite directions:
GOT2 loss: ↓ aspartate
GOT1 loss: ↑ aspartate

Both led to a block in red blood cell maturation—so, not just about aspartate levels!

4/ Approach
Narges, et al. deleted GOT1 or GOT2 globally or in erythroid cells in mice. Loss of either enzyme — or both — led to anemia and blocked red cell development at early progenitor stages.

3/ Background
RBCs are constantly replenished (~200B/day), but the metabolic needs of this process are unclear. Profiling shows: Aspartate rises during erythropoiesis. Does aspartate metabolism drive red cell formation? 🤔

2/ Working with the @YatrikShahLab and Khoriaty labs, Narges discovered a previously unrecognized, critical role for aspartate aminotransferases (GOT1 & GOT2) in red blood cell (RBC) production, with implications for anemia therapy.

Aspartate transaminases are required for blood development Red blood cells (RBCs) have a limited lifespan of approximately 120 days. This necessitates continuous RBC production, resulting in ∼200 billion new RBCs made per day to maintain oxygen delivery. Desp...

Excited to share a new story from the Lab! 🚨🩸

🧵 1/ Aspartate transaminases control blood development, by Narges Pourmandi, et al

www.biorxiv.org/content/10.1...

Opinion | Autism Has Never Been One Thing We’ve come too far to go back to a time when autism was defined solely in terms of deficits and mothers were made to feel guilty.

In @nytopinion.nytimes.com

The Trump administration’s autism project “is built on the premise that an autism diagnosis is a terrible tragedy and that scientists and doctors have failed,” Roy Grinker, a cultural anthropologist and the father of an autistic child, says. “But science has not failed.”

Rewiring of cortical glucose metabolism fuels human brain cancer growth - Nature The cortex fuels essential physiological processes with glucose-derived carbon, while gliomas fuel their aggressiveness by rerouting glucose carbon pathways and scavenging alternative carbon sources s...

New discovery from our team defining how human brain cancers rewire the metabolism of the normal brain published this week @nature.com and led by stellar postdoc Drew Scott (comentored by @lyssiotislab.bsky.social and currently on job market with a K99/R00). www.nature.com/articles/s41...

Thanks for the hype! 🙏🏼

Glioblastoma depends on the amino acid serine as a fuel source & serine-deficient diet slows tumor growth in mice @nature.com @dnagrathlab.bsky.social @lyssiotislab.bsky.social
www.nature.com/articles/s41...
www.nature.com/articles/d41...
www.nature.com/articles/d41...

Rewiring of cortical glucose metabolism fuels human brain cancer growth - Nature The cortex fuels essential physiological processes with glucose-derived carbon, while gliomas fuel their aggressiveness by rerouting glucose carbon pathways and scavenging alternative carbon sources s...

Rewiring of cortical glucose metabolism fuels human brain cancer growth

www.nature.com/articles/s41...

Congrats to the many involved, including @lyssiotislab.bsky.social and @dnagrathlab.bsky.social

Dietary changes could provide a therapeutic avenue for brain cancer A team of researchers from Michigan Medicine tracked how glucose is used in glioblastoma tumor cells. They showed that dietary interventions can slow brain cancer growth in mice.

A massive team effort by U-M researchers have found that glioblastoma cells rewire how they use sugar, which can be targeted in mice to slow tumor growth and improve treatment responses. @lyssiotislab.bsky.social @dnagrathlab.bsky.social

Learn more: michmed.org/MD2X2.

CDC leaders who resigned said RFK Jr. undermined vaccine science, risking lives As the CDC reels from departures, White House appoints Jim O’Neill as acting director.

Three senior leaders who resigned in protest told The Post they were asked to participate in an unscientific vaccine recommendation process that they believe could harm the health of Americans.

More from @lenasun.bsky.social @laurenweberhp.bsky.social @davidovalle.bsky.social

🎁: wapo.st/46aNJB0

Ok so does anyone know anything about the NSF GRFP? Has anyone made any statement?

Grad students keep telling me they’re writing it and I’m like discouraging them from spending time on this…. But do we have any actual information?

Assistant/Associate Professor - Tenure Track - Physiology - University of Michigan, Ann Arbor job with University of Michigan Department of Molecular & Integrative Physiology | 674815 Tenure track assistant/associate professor in the Department of Molecular & Integrative Physiology at the University of Michigan Medical School.

Our department is recruiting a new tenure track Assistant/Associate Professor. Come join the #1 physiology department in the country and some awesome colleagues doing high impact science and training the next generation of scientists

jobs.sciencecareers.org/job/674815/a...

Congratulations 2025 Gilliam Fellows and Advisors! 🎉

The Gilliam Fellows Program launches promising PhD students into impactful scientific research careers while fostering inclusive training environments.
Through this program, HHMI supports both graduate students and their faculty thesis advisors.

I am so happy to join the HHMI Gilliam community, keep working in cancer metabolism, and continuing my passions in scientific outreach and communication!

Huge thanks to all of my current and past mentors!
@lyssiotislab.bsky.social, @ajdiazphd.bsky.social, Dr. Yatrik Shah

Photo of a tv. Onscreen a woman holds an axe with a periodic table visible behind.

Buffy is so old there were only 103 named elements, we’re at 118 now.

(Yes I pause every show that has a periodic table to see if its period accurate)

May the odds be ever in your favor.
4% payline at the NCI.

www.cancer.gov/grants-train...

PO just confirmed that our 5th percentile R01 is not getting funded. Past NCI Payline at 4 percent. Cant believe it.

Fifteen years later, Science retracts ‘arsenic life’ paper despite study authors’ protests Belated decision on widely disputed 2010 study pleases some critics but puzzles and dismays others

Science finally retracts the Arsenic life paper www.science.org/content/arti...

Look forward to seeing you there 🙌🏼

Congrats on this awesome work! (Got ya on Twitter, here too now 😊)