Alon Millet

39 posts

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Alon Millet

Alon Millet

@AlonMillet

PhD student in the Tavazoie Lab @RockefellerUniv via @cbm_student | @MCDB_Yale BS/MS '20 | 75% immuno, 25% comp bio, 100% baking bread | 🏳️‍🌈

Manhattan, NY Katılım Nisan 2015
49 Takip Edilen100 Takipçiler
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Alon Millet
Alon Millet@AlonMillet·
Thrilled to cap off the year with the first paper of my PhD, out today in @ImmunityCP! We describe a population of exhausted-like microglia that accumulate in #Alzheimer's in both humans and mice in an age- and APOE4-dependent manner authors.elsevier.com/c/1iL2Z3qNrUu4… Tweetorial below🧵
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Alon Millet
Alon Millet@AlonMillet·
Was an honor to contribute to this tremendous study co-led by the brilliant duo of @gadmark and @shanshanliu1218. Check out the thread below to learn more about how SLC33A1 works to maintain ER redox balance!
Gad@gadmark

Thrilled to share our new paper: SLC33A1 is the long-sought ER GSSG exporter, maintaining redox homeostasis in the ER. Huge congratulations to my co-first author @shanshanliu1218 and my PIs @KivancBirsoy and @HiteLabMSKCC for leading this work. nature.com/articles/s4155… 🧵 1/9

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Alon Millet
Alon Millet@AlonMillet·
Was a joy getting to work with Hsi-Wen and @nicoledelgaudio on this beautiful story! Metastasizing breast cancer cells experience many stressors; now we know mitochondrial GSH is critical in regulating the ISR and protecting cancer during early colonization. More below:
Kivanc Birsoy@KivancBirsoy

New work from our lab describing a role for mitochondrial glutathione in breast cancer metastasis ⁦@nicoledelgaudio⁩ ⁦@RockefellerUniv⁩ aacrjournals.org/cancerdiscover…

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Alon Millet
Alon Millet@AlonMillet·
@shabanamehtab @KrishnanYamuna @ImmunityCP Thanks for the questions! Both TIM and DAM are induced by AD-associated inflammation but are completely distinct states. And we find that TIM are strongly enriched in males in the ROSMAP DLPFC-2 dataset (n = 465) - see Figure 4G in the paper for more.
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Alon Millet
Alon Millet@AlonMillet·
@EricTopol @RockefellerUniv @SohailTavazoie Thanks so much for sharing our work, Eric! For anyone who wants to read more, I have a tweetorial and the free access link here: twitter.com/AlonMillet/sta…
Alon Millet@AlonMillet

Thrilled to cap off the year with the first paper of my PhD, out today in @ImmunityCP! We describe a population of exhausted-like microglia that accumulate in #Alzheimer's in both humans and mice in an age- and APOE4-dependent manner authors.elsevier.com/c/1iL2Z3qNrUu4… Tweetorial below🧵

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Alon Millet
Alon Millet@AlonMillet·
@nich218548 @ImmunityCP I think it's unlikely. NPC is pathologically very distinct from AD, even if NPC is sometimes called childhood AD. Microglia are indeed dysregulated in NPC, but I think the causative link is more tenuous than in AD or other neuroinflammatory conditions like MS.
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Alon Millet
Alon Millet@AlonMillet·
@LukensJohnR Thanks for sharing our work! I've put out a tweetorial with a free-access link here for anyone who wants to learn more: twitter.com/AlonMillet/sta…
Alon Millet@AlonMillet

Thrilled to cap off the year with the first paper of my PhD, out today in @ImmunityCP! We describe a population of exhausted-like microglia that accumulate in #Alzheimer's in both humans and mice in an age- and APOE4-dependent manner authors.elsevier.com/c/1iL2Z3qNrUu4… Tweetorial below🧵

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John Lukens
John Lukens@LukensJohnR·
An exhausted-like microglial population accumulates in aged and APOE4 genotype Alzheimer’s brains: Immunity cell.com/immunity/fullt…
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Alon Millet
Alon Millet@AlonMillet·
@SohailTavazoie @Jhledo @cbm_student @RockefellerUniv We’re really excited about this work and think it opens the door for lots of downstream questions. If you want to chat or have any questions about the paper/this tweetorial/anything else, my DMs are open!
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Alon Millet
Alon Millet@AlonMillet·
So what's the big picture? We think there are a few takeaways, and we speculate a little bit about some of them in the discussion of the manuscript.
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Alon Millet
Alon Millet@AlonMillet·
When we looked at microglial subclusters, the story was clear: aducanumab's recruitment of adaptive immune cells was mediated largely by increased signaling from effector-hi TIM!! This subset of dysfunctional microglia turns out to orchestrate the response to aducanumab🤯
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Alon Millet
Alon Millet@AlonMillet·
The takeaway here is that APOE4 mice have their amyloid clearance weakened twice over: they have more TIM than other genotypes, *plus* their TIM are especially dysfunctional. We think this has clear implications for Alzheimer’s pathology and progression.
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Alon Millet
Alon Millet@AlonMillet·
We then looked at ligand-receptor interactions performed by microglia in the brains of these mice. Surprisingly, we found that while microglia from APOE3 and APOE4 became more inflammatory upon treatment, aducanumab actually *inhibited* microglial function in APOE2 mice!!
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Alon Millet
Alon Millet@AlonMillet·
We therefore treated 60-week-old AD mice bearing human APOE variants with aducanumab or an isotype control before harvesting immune cells from their brains for scRNAseq. Interestingly, TIM in aducanumab-treated animals shifted profoundly from effector-lo to effector-hi!
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Alon Millet
Alon Millet@AlonMillet·
Our final question was what aducanumab, a recently approved (and controversial) therapeutic for AD would do to the TIM state. We knew aducanumab recruited adaptive immune populations and were curious if this could somehow jump-start TIM out of their defective state.
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Keşfet

@gadmark @shanshanliu1218 @nicoledelgaudio @10xGenomics @shabanamehtab @ImmunityCP @EricTopol @RockefellerUniv