Justin Perry - Perry Lab

It does raise the question of why the thymus hate? There should be a campaign to stop the thymus hate!

I think my lab works on immunometabolism 🤔🤷‍♂️🤣

Yuval Levin: Have an Argument.
Disengagement—not disagreement—is the real failure of our politics.
www.thefp.com/p/yuval-levi...

If you can't say that political violence, especially murdering someone in cold blood because you disagree with them, is not only morally wrong but anathema to a free country, then I would encourage you to immediately log off and take time for self-reflection.

Cool! Have you built in a way to integrate published phenotypes?

Fructose, Microglia, Anxiety & Brain Development | Justin Perry | 249 Cellular clean up by immune cells and how early-life fructose exposure leads to neurodevelopmental problems.

I was interviewed by Nick Jahomes on the Mind & Matter podcast about our study in @nature.com. Nick does a great job asking questions & explaining nitty gritty. Please take time to listen to the episode & if you like it, consider supporting Nick's efforts. mindandmatter.substack.com/p/fructose-m...

Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology - Environmental Health Background Acetaminophen is the most commonly used over-the-counter pain and fever medication taken during pregnancy, with > 50% of pregnant women using acetaminophen worldwide. Numerous well-designed...

Here's what I assume the study is in re: acetaminophen. It's a statistical analysis of a few dozen studies, to be clear, where the majority (especially the high quality ones) show a positive association. Reputable investigators. ehjournal.biomedcentral.com/articles/10....

What's the concern? They awarded it this most recent cycle. www.research.gov/grfp/Login.do

@wcm-imp.bsky.social @weillcornell.bsky.social @mskcancercenter.bsky.social

Congratulations to Ana @anaccodo.bsky.social in my lab and the other awardees. It is a really great acknowledgement of excellent trainees doing cool science.

Makes me miss the talented people back home in AK. Was just back at Forest Fair, another reminder of how great it is there.

It's official. I'm happy to announce that I have been promoted to Associate Member @mskcancercenter.bsky.social. It is sincere when I say that this would not have been possible w/o the incredible work of the members of my lab. In fact, exciting news about them coming soon. Stay tuned.

Today we remember our founding & the principles that this great nation was built on, that although we do not always live up to its ideals, it is those ideals, especially the liberty that pluralism affords, that will remain a beacon of hope for a more perfect union. As Madison wrote in Federalist 10:

Interesting. Congrats.

Kupffer cell programming by maternal obesity triggers fatty liver disease - Nature In a mouse model, maternal obesity during pregnancy can lead to fatty liver disease in the offspring, driven by aberrant developmental programming of Kuppfer cells.

New from @masslab.bsky.social @unibonn.bsky.social @immunosens.bsky.social out @natureportfolio.nature.com also shows maternal diet affects offspring macrophage function & disease susceptibility.

Mass Lab study: www.nature.com/articles/s41...
Our study: rdcu.be/eqx2G

Early life high fructose impairs microglial phagocytosis and neurodevelopment Nature - Exposure of mice to high fructose during gestation or early postnatal life causes decreased microglial phagocytosis during brain development and leads to anxiety-like behaviour in...

Update: Free-ish link: rdcu.be/eqx2G

3) A bit hidden in the supplement, but we propose a mostly-observational, not at all proven, mechanism of action in which HK2 localization is responsible for the defect in phagocytosis and altered metabolism. Very excited to work on this and the role of GLUT5/fructose in aging!

2) Quantitation of fructose in the brain and important clarification that our effect did not seem to be due to circulating- or CNS-derived glucose (polyol pathway) or circulating lactate.

What was new in the revision? A few things:
1) We created SLC2A5 (GLUT5) floxed mice to delete the transporter from myeloid cells during embryogenesis. This completely reversed the phagocytosis, metabolism, and behavioral phenotypes due to high fructose exposure.

High-Fructose Diet Harms Neurodevelopment and Leads to Anxiety in Mice, MSK Study Finds A new laboratory study from MSK is shedding light on the mechanisms by which high fructose consumption early in life may directly impact brain development and increase the risk of anxiety disorders la...

@mskcancercenter.bsky.social has a nice writeup on it here: www.mskcc.org/news/high-fr...
And we have a preprint here: pubmed.ncbi.nlm.nih.gov/37645894/ with an explainer here x.com/JustinPerryP...

Out today from The Perry Lab, our work suggesting how exposure to high fructose in pregnant mice or developing neonates directly affects neurodevelopment. In @natureportfolio.nature.com www.nature.com/articles/s41... @mskcancercenter.bsky.social @weillcornell.bsky.social.

WNK1 mediates M-CSF-induced macropinocytosis to enforce macrophage lineage fidelity Nature Communications - Tissue-resident macrophages (TRM) are important mediators of local immunity. Here the authors show that the deficiency or inhibition of a kinase, WNK1, unlinks macrophage...

Cool story. Wonder what this means when considering our finding that microglia (numbers defined by conventional protein markers, anyway) were surprisingly unaffected. rdcu.be/eoaRm

What are these other factors? 🤔

Cell ‘drinking’ and enzyme activation shape immune cell fate New study shows that a specific growth factor causes early-stage immune cells (macrophage precursors) to ‘drink’, which activates a special enzyme. This cell drinking and enzyme activation determines ...

Naturally, lots of questions remaining, including about how WNK1 is actually functioning to inform macrophage lineage commitment. Nevertheless, excited to see this story out. It's one of the best I have ever been a part of. @edinuni-irr.bsky.social writeup is here: edin.ac/3FtYS5B

5. Alissa then performed a whole bunch of experiments to demonstrate that WNK1 acts downstream of CSF1R (M-CSF receptor) to inform macrophage differentiation.

4. M-CSF-stimulated macropinocytosis is required for differentiation of myeloid progenitors into macrophages🤯.

3. M-CSF stimulates macropinocytosis across all myeloid progenitor and monocyte populations. Props to Alissa for setting up this beautiful system to analyze macropinocytosis in non-adherent cells.

2. 2. Neonatal and hematopoietic myeloid progenitors (MPs) lacking WNK1 (or with WNK kinase inhibited) differentiate into neutrophils instead of macrophages in response to M-CSF🤯. Also true for human MPs. Monocytes lacking WNK1 also fail to differentiate into macrophages.

The paper is a behemoth, including a ton of interesting data in the supplement. Out of the interest of time, I will sum it briefly.
1. Mice that conditionally lack WNK1 under a CSF1R promoter-driven Cre die by 4 weeks of age because the lack tissue-resident macrophages.

New study by Alissa Trzeciak in The Perry Lab @mskcancercenter.bsky.social is out! The best way to explain the journey is if I compared it to the Director's Cut of the Lord of the Rings trilogy. Let's just say, it wasn't submitted in March 2025.
Link: rdcu.be/eoaRm
Writeup: edin.ac/3FtYS5B

Embarrassingly slow to post this, but The Perry Lab @mskcancercenter.bsky.social has graduated its first PhD student! It was a great couple of weeks for Shasha, a @weillcornell.bsky.social IMP student. He received The Schmidt Science Fellowship, had his paper accepted (out soon), and defended!