Sophia Shi (@sophmshi) / X

Sophia Shi

53 posts

Sophia Shi

@sophmshi

Rowland Fellow & PrincipaI Investigator @Harvard | brain aging + glycobiology | shigroup.org

United States

Joined November 2019

Pinned
Sophia Shi
@sophmshi
Feb 26, 2025
Excited to share our new study in @Nature! We uncover how the vascular glycocalyx—a carbohydrate-rich coating on blood vessels—plays a crucial role in brain health and aging. A @wysscoray & @CarolynBertozzi labs collaboration. 🍭🧠 #glycotime (1/12)
Glycocalyx dysregulation impairs blood–brain barrier in ageing and disease
From nature.com
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Sophia Shi
@sophmshi
Apr 22, 2025
Thrilled to share that I’ll be launching my independent lab as a Rowland Fellow & PI @Harvard this Fall! Our lab will investigate how glycans (sugar molecules) modulate brain aging and neurodegeneration. We’re recruiting motivated scientists at all levels to join the team! 🍬🧠✨
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Sophia Shi
@sophmshi
Aug 20, 2025
Sharing two new detailed protocols from our recent Cerebrovascular Glycocalyx paper in @Nature: 🪢 Brain vessel isolation from mice and human tissues for imaging and analysis. 🩸🚧 Luminal cerebrovascular proteomics for mapping therapeutic targets, BBB transporters, and more.
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Sophia Shi
@sophmshi
Jun 10, 2025
Thanks Eric! Grateful for this feature
Eric Topol
@EricTopol
Jun 10, 2025
Spotlight on Sophia Shi's outstanding work on brain aging today w/@CarolynBertozzi and @wysscoray @Stanford genomicpress.kglmeridian.com/view/journals/…
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Sophia Shi
@sophmshi
Feb 26, 2025
Replying to @sophmshi
It was remarkable to us that modulating glycans in the brain vasculature could have such profound impacts on brain health and cognitive function. This opens new avenues for understanding and treating neurodegenerative diseases. 🧠🔬(11/12)
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Sophia Shi
@sophmshi
Feb 26, 2025
Replying to @sophmshi
Thank you for making it this far! Huge thank you to my wonderful co-authors: Ryan, @ShonJs, Francisco, Josi, Micaiah, Lulin, @NannanLu3, Bryan, Jian, Ning, Tom, Windy, Myriam, and incredible mentors @wysscoray & @CarolynBertozzi. 🍬🧠😊 #glycobraintime (12/12)
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Sophia Shi
@sophmshi
Feb 26, 2025
Replying to @sophmshi
The glycocalyx is a sugar-rich meshwork that forms the first barrier between the blood and brain. Despite its crucial location, its roles in cerebrovascular function, brain health, and aging are poorly understood. (2/12)
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Sophia Shi
@sophmshi
Feb 26, 2025
Replying to @sophmshi
Using electron microscopy with lanthanum staining, we found that the cerebrovascular glycocalyx is severely diminished with age in mice 😮. This raised a big question: Does glycocalyx dysregulation drive vascular dysfunction & poor brain health in aging and disease? (3/12)
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Sophia Shi
@sophmshi
May 12, 2023
Thank you, @BuckInstitute ! It was a pleasure visiting your beautiful campus, and thank you to the organizers and other speakers for all of the amazing talks!
Buck Institute
@BuckInstitute
May 11, 2023
The glycocalyx is a layer of glycans that line the BBB. Sophia Shi from #Stanford discussed how dysregulation of the glycan layer is implicated in neurodegeneration. Finding ways to preserve the glycocalyx might prevent neurodegenerative diseases. #BAAM23
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Sophia Shi
@sophmshi
Feb 26, 2025
Replying to @sophmshi
✨Remarkably, restoring mucin-type O-glycans to cerebrovascular endothelial cells via gene delivery of C1galt1 and B3gnt3 improved cerebrovascular integrity in aged mice. (9/12)
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Sophia Shi
@sophmshi
Feb 26, 2025
Replying to @sophmshi
We profiled changes in glycan composition on brain endothelial cells in aging and Alzheimer's Disease (AD) and found many alterations. Notably, glycosaminoglycans were largely upregulated, while mucin-domain glycoproteins were consistently downregulated with age and AD. (4/12)
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Sophia Shi
@sophmshi
Feb 26, 2025
Replying to @sophmshi
To understand their functions on the vasculature, we used StcE mucinase to enzymatically remove mucins, which led to striking glycocalyx depletion and brain bleeding 🩸. This revealed a critical role for mucins in maintaining cerebrovascular integrity. (6/12)
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Sophia Shi
@sophmshi
Feb 26, 2025
Replying to @sophmshi
💥Indeed, knocking down C1galt1, a key mucin biosynthetic enzyme downregulated in aging and AD, led to increased cerebrovascular leakage of blood-derived molecules like albumin and IgG, which can harm the brain and contribute to neurodegeneration. (8/12)
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Sophia Shi
@sophmshi
Feb 26, 2025
Replying to @sophmshi
Mucin-domain glycoproteins contain dense regions of O-glycosylation, similar to the mucins found in our gut and respiratory mucus barriers 🫁🚧. However, these glycoproteins remain largely unstudied on the brain vasculature. (5/12)
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