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Anne Carpenter @drannecarpenter.bsky.social · 1h

Interesting connection!

Anne Carpenter @drannecarpenter.bsky.social · 1h

Mostly no! Which i am excited about, because existing treatments are not great for most patients. So we’d love to have medicines with a very different mechanism than the existing ones.

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Reposted by Anne Carpenter

Prof Jenny Rohn @jennyrohn.bsky.social · 4h

People often dismiss cell biology as just “looking at stuff”, which makes seminal discoveries like this even sweeter. Congrats @drannecarpenter.bsky.social and team

Anne Carpenter @drannecarpenter.bsky.social · 21h

15 years in the making, we confirmed that mitochondria - the powerhouse of the cell - have an unusual localization in patients who experience psychosis (including schizophrenia and bipolar disorders). You’ll never guess what kind of patient cells we used to make this discovery… 🧵

mitochondria from bipolar patients are closer to the nucleus in these images; control patients' are spread out further

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Anne Carpenter @drannecarpenter.bsky.social · 3h

Awww 🥰

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Anne Carpenter @drannecarpenter.bsky.social · 4h

Psoriasis!

www.everydayhealth.com/skin-conditi...

Psoriasis and Bipolar Disorder: Understanding Their Connection

Explore the connection between psoriasis and bipolar disorder, their shared risk factors, and strategies for managing both conditions effectively.

www.everydayhealth.com

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Anne Carpenter @drannecarpenter.bsky.social · 5h

Oooh, that’s really consistent with this growing story that phenotypes, not just genotypes, drive cancer!

pubmed.ncbi.nlm.nih.gov/39112299/

The origin of novel traits in cancer - PubMed

The traditional view of cancer emphasizes a genes-first process. Novel cancer traits arise by genetic mutations that spread to drive phenotypic change. However, recent data support a phenotypes-first ...

pubmed.ncbi.nlm.nih.gov

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Anne Carpenter @drannecarpenter.bsky.social · 5h

Interesting! I wonder how many diseases our other conforms are associated with subtle clues that aren’t terrible symptoms so nobody records them or notices them. I notice a lot of very smart people tend to have sensitive skin.

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Anne Carpenter @drannecarpenter.bsky.social · 5h

The change is subtle and not consistent for all patients so this isn’t useful as a diagnostic. Instead, we are excited because we can now test thousands of candidate drugs in skin cells to see if any will make the mito location more normal. Which could then be developed and tested in patients.

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Anne Carpenter @drannecarpenter.bsky.social · 5h

I’d think fewer mito at the synapses means LESS signaling and therefore depression, not psychosis. But weirdly, researchers recently found that mito in brain cells consume energy (ATP) rather than produce it! So that makes sense, fewer mito would mean more energy near synapses and more signaling.

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Anne Carpenter @drannecarpenter.bsky.social · 5h

Brain cells (neurons) have long skinny arms with synapses near the ends. It’s speculation, but we think that if mito aren’t getting to the very ends of those arms, that could cause signaling problems for the brain cells.

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Anne Carpenter @drannecarpenter.bsky.social · 5h

For those patients the mito tend to stay away from the cell edge (in skin cells). Skin cells are relatively compact so it probably doesn’t matter too much. But we see the same pattern in actual brains (in our prior paper) where we bet the mito location matters a lot more (& may be causing symptoms)…

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Anne Carpenter @drannecarpenter.bsky.social · 5h

Thrilled to! Mitochondria are a part of the cell that helps convert food into energy. Normally they are distributed throughout the cell (except for the nucleus, where the DNA/genes are). But we found a subtle shift in location for patients with psychosis (including schizophrenia & bipolar)…

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Anne Carpenter @drannecarpenter.bsky.social · 17h

Oh interesting, so do I understand that here, you're not looking at patients with any particular disease, but you found that mito are literally IN the nucleus? Or are they just attached closely to the exterior of the nucleus?

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Anne Carpenter @drannecarpenter.bsky.social · 18h

No clue! But Bruce Cohen and Donna McPhie might have an opinion (they're offline!)

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Anne Carpenter @drannecarpenter.bsky.social · 18h

Yes!! We've seen it as part of our prior study: pubmed.ncbi.nlm.nih.gov/20566748/

Abnormalities in mitochondrial structure in cells from patients with bipolar disorder - PubMed

Postmortem, genetic, brain imaging, and peripheral cell studies all support decreased mitochondrial activity as a factor in the manifestation of Bipolar Disorder (BD). Because abnormal mitochondrial m...

pubmed.ncbi.nlm.nih.gov

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Anne Carpenter @drannecarpenter.bsky.social · 21h

Thanks to the funders who believed in us, enabling us to complete this work in pieces over time:
NIH NIGMS, Merkin Institute, BroadIgnite, BBRF, Harvard-MIT Neurodiscovery program, and the Program for Neuropsychiatric Research at McLean Hospital.

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Anne Carpenter @drannecarpenter.bsky.social · 21h

Congrats to the project team across McLean Hospital & Broad Institute! First authors: Marzieh Haghighi & Donna McPhie! Co-senior author Bruce Cohen. Team: Mohammad Rohban, Erin Weisbart, David Logan, Kyle Karhohs, Jessica Ewald, Johan Fredin Haslum, Beth Cimini, Shantanu Singh.

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Anne Carpenter @drannecarpenter.bsky.social · 21h

This means that we can screen for potential novel drugs for schizophrenia and bipolar disorder in easily-grown skin cells, using mitochondria as a simple readout. In fact, a team at NIH’s NCATS is working on this now! Stay tuned.

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Anne Carpenter @drannecarpenter.bsky.social · 21h

We then queried cell image databases to find chemicals and genetic perturbations that change mitochondrial localization in either direction, towards or away from the nucleus. Many have known involvement in mental function!

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Anne Carpenter @drannecarpenter.bsky.social · 21h

This mislocalization, in which mitochondria cluster too close to the nucleus in the middle of cells, may deprive cells, including brain cells, of energy and metabolites needed for growth, function, and repair.

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Anne Carpenter @drannecarpenter.bsky.social · 21h

That seems really odd, but lots of cells share lots of components and processes that are used in different ways in different cell types. And not-fun fact: psychotic symptoms are associated with skin abnormalities.

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Anne Carpenter @drannecarpenter.bsky.social · 21h

… unless you’ve heard me talk about it, which I’ve done a lot over the past decade :D Including in this Quanta video: youtu.be/KDQFUmDJ3nY?...

But now this project is finally preprinted!! The answer is skin cells. Skin cells!
www.biorxiv.org/content/10.1...

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Anne Carpenter @drannecarpenter.bsky.social · 21h

15 years in the making, we confirmed that mitochondria - the powerhouse of the cell - have an unusual localization in patients who experience psychosis (including schizophrenia and bipolar disorders). You’ll never guess what kind of patient cells we used to make this discovery… 🧵

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Reposted by Anne Carpenter

broadmpg.bsky.social @broadmpg.bsky.social · 10d

The recording of "Illuminate variant impact with images" by @drannecarpenter.bsky.social‬ and Runxi Shen is now available:
youtu.be/l8y00jKXJx4 This talk is part of @broadinstitute's MPG Primer series. For more info, check out broad.io/MPGPrimer

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Reposted by Anne Carpenter

Ashley C. Ford @smashfizzle.bsky.social · 13d

In Somebody’s Daughter, I wrote about a middle school teacher who was super kind to me, and how he influenced me to expand on my preoccupation with reading by encouraging me to write as well. Earlier today, at the Indiana State Library, his adult daughter was in my nonfiction writing workshop 🥹

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