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hyejungwon.bsky.social
Hyejung Won
@hyejungwon.bsky.social
220 followers 71 following 24 posts
Associate Professor at UNC Chapel Hill Neurogenetics wonlab.org
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hyejungwon.bsky.social
Hyejung Won @hyejungwon.bsky.social · Jan 27
1/ I am beyond thrilled to share our new paper in @CellCellPress! We explored the regulatory principles underlying pleiotropy in psychiatric disorders.
www.cell.com/cell/abstrac...
Massively parallel reporter assay investigates shared genetic variants of eight psychiatric disorders
High-throughput experimental validation of genetic variants linked to eight psychiatric disorders reveals the regulatory mechanisms underlying variants with pleiotropic and disorder-specific effects.
www.cell.com
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hyejungwon.bsky.social
Hyejung Won @hyejungwon.bsky.social · Jul 2
Thanks Leo! It was lovely to meet you again!
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hyejungwon.bsky.social
Hyejung Won @hyejungwon.bsky.social · Jul 2
Thanks so much Keri for inviting me ❤️ It was a great pleasure to visit Lieber and meet so many amazing scientists!
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Reposted by Hyejung Won
martinowk.bsky.social
Keri Martinowich @martinowk.bsky.social · Jun 24
Phenomenal talk from @hyejungwon.bsky.social who is visiting us @lieberinstitute.bsky.social for the day. Groundbreaking work w/ important implications and roadmap for using rapidly emerging information on psychiatric genetics to prioritize variants and understand their impact on 🧠 function
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Reposted by Hyejung Won
dougfowler.bsky.social
Doug Fowler @dougfowler.bsky.social · May 15
Our "Atlas of Variant Effects 2030 Roadmap" is live: zenodo.org/records/1542...

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Atlas of Variant Effects 2030 Roadmap: resolving human variants of uncertain significance
At the Clinical Atlas of Variant Effects meeting (CLAVE meeting, July 2024, Pittsburgh USA), we developed recommendations for a draft atlas that can be realized by 2030, with a focus on empowering gen...
zenodo.org
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Reposted by Hyejung Won
sj-marzi.bsky.social
Sarah Marzi @sj-marzi.bsky.social · May 27
How does APOE change your risk of developing Alzheimer's disease? At least partially by changing the function of immune cells in your brain 🧠🧬

New paper out in @natcomms.nature.com today: www.nature.com/articles/s41...

@ukdri.ac.uk @kingsioppn.bsky.social @imperialbrains.bsky.social
https://nature.com/articles/s4146…
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hyejungwon.bsky.social
Hyejung Won @hyejungwon.bsky.social · May 14
Huge congrats Debby! This was a lovely story when you presented at GRC ❤️
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hyejungwon.bsky.social
Hyejung Won @hyejungwon.bsky.social · May 1
Huge congrats Alexi and Sarah 🎉
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Reposted by Hyejung Won
kampmann.bsky.social
Martin Kampmann @kampmann.bsky.social · Apr 16
Silencing of transgenes during iPSC differentiation is a frequent problem. 🧬🫢

Check out the piggyBac system below, which has resisted silencing in many protocols across many labs. 💪

Excited that our lab could contribute to this team effort led by @tuenaka.bsky.social & Marius Wernig!
tuenaka.bsky.social
Takeshi Uenaka @tuenaka.bsky.social · Apr 15
Losing sleep over #iPSC transgene silencing after differentiation?
Same here — too many times😭

So we built a PiggyBac construct that resists silencing.
Expression stays ON, even after differentiation.

Our #preprint is out👇
🔗 www.biorxiv.org/content/10.1...

Supported by @cziscience.bsky.social
Prevention of Transgene Silencing During Human Pluripotent Stem Cell Differentiation
While high and stable transgene expression can be achieved in undifferentiated pluripotent stem cells, conventional transgene expression systems are often silenced upon differentiation. Silencing occu...
www.biorxiv.org
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Reposted by Hyejung Won
fg-pgc.bsky.social
PGC Functional Genomics @fg-pgc.bsky.social · Mar 11
Watch the video📽️attached to see what each of these awesome #FemsinSTEM are up to!

🧵3/3
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hyejungwon.bsky.social
Hyejung Won @hyejungwon.bsky.social · Mar 6
Marija, I am so much happy for you! Huge congrats! 😍
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hyejungwon.bsky.social
Hyejung Won @hyejungwon.bsky.social · Feb 28
Hello, it is because borderline disorder GWAS is not well powered: i.e. it does not have any hits (dots) above the red line in figure 2: www.nature.com/articles/tp2.... This means that there are not robust and reliable genomic regions that we can chase after for functional analysis.
Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia - Translational Psychiatry
Translational Psychiatry - Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia
www.nature.com
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hyejungwon.bsky.social
Hyejung Won @hyejungwon.bsky.social · Feb 27
This is soooo cool Pedro! Huge congrats!
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Reposted by Hyejung Won
cedricboeckx.bsky.social
Cedric Boeckx @cedricboeckx.bsky.social · Feb 12
Very good new preprint by @nanamatoba.bsky.social @hyejungwon.bsky.social @steinlab.bsky.social, using a Massively Parallel Reporter Assay to gain insight into regulatory elements associated with inter-individual differences in cortical structure (Wnt response sensitivity plays a prominent role)🧪🧠🧬
Massively parallel assessment of gene regulatory activity at human cortical structure associated variants
Genetic association studies have identified hundreds of largely non-coding loci associated with inter-individual differences in the structure of the human cortex, though the specific genetic variants ...
www.biorxiv.org
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hyejungwon.bsky.social
Hyejung Won @hyejungwon.bsky.social · Jan 28
15/ Last but not least, I'd like to thank fabulous first authors, Sool Lee, Jessica McAfee, and Jiseok Lee; great collaborators, Pat Sullivan, Adriana Beltran, @markgerstein.bsky.social, Alan Boyle; and a fantastic editor, Scott Behie!
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hyejungwon.bsky.social
Hyejung Won @hyejungwon.bsky.social · Jan 28
Thanks so much!
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hyejungwon.bsky.social
Hyejung Won @hyejungwon.bsky.social · Jan 28
Yay thanks! You deserve a credit here 😆
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hyejungwon.bsky.social
Hyejung Won @hyejungwon.bsky.social · Jan 28
14/ There’s much more in the full manuscript, including findings on Alu elements with gene regulatory activity and CRISPR validation. Check it out here for full access: authors.elsevier.com/a/1kU9ZL7PXq...
authors.elsevier.com
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hyejungwon.bsky.social
Hyejung Won @hyejungwon.bsky.social · Jan 28
13/ Together, our findings suggest pleiotropy arises from the functional properties of target genes and proteins, including prolonged gene activity during neuronal differentiation and higher protein connectivity in PPI networks.
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hyejungwon.bsky.social
Hyejung Won @hyejungwon.bsky.social · Jan 28
12/ PPI networks were a recurring theme: mDis3-bound transcription factors, mDis3 proteins, and even downstream effectors all showed higher connectivity in PPI networks. Connectivity in these networks seems critical to how pleiotropic variants exert their effects.
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hyejungwon.bsky.social
Hyejung Won @hyejungwon.bsky.social · Jan 28
11/ We also investigated protein-protein interaction (PPI) networks. mDis3 proteins were significantly more interconnected than mDis1 proteins. This implies pleiotropic proteins may amplify their effects through network connectivity, rippling through molecular pathways.
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hyejungwon.bsky.social
Hyejung Won @hyejungwon.bsky.social · Jan 28
10/ This suggests that mDis3 variants target genes with broader or longer activity across excitatory neuronal differentiation, potentially driving multiple downstream effects. These temporal differences may explain part of the functional diversity seen in pleiotropy.
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hyejungwon.bsky.social
Hyejung Won @hyejungwon.bsky.social · Jan 28
9/ We next examined the functional properties of variants and their target genes. Both mDis1 and mDis3 variants were enriched in the excitatory neuronal lineage. In this lineage, mDis1 genes were often expressed in a single cell type, while mDis3 genes showed prolonged, multi-cell-type expression.
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hyejungwon.bsky.social
Hyejung Won @hyejungwon.bsky.social · Jan 28
8/ Next, we wondered if mDis3 variants have more complex regulatory connectivity (e.g., linking to multiple genes). Again, no significant differences were found between mDis3 and mDis1 loci in the number of genes connected to emVars.
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hyejungwon.bsky.social
Hyejung Won @hyejungwon.bsky.social · Jan 28
7/ First, we asked if mDis3 loci simply have more emVars than mDis1 loci. The number of emVars didn’t differ between mDis3 and mDis1 loci. So, the extent of pleiotropy wasn’t explained by the number of variants with regulatory activity.
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hyejungwon.bsky.social
Hyejung Won @hyejungwon.bsky.social · Jan 27
6/ Why exclude 2-disorder variants? Many were linked to bipolar and schizophrenia, which have high genetic correlation (>0.7). This made it hard to determine if they were truly pleiotropic or just driven by shared biology between these two highly related disorders.
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