When we first isolated FOXP2 & implicated it in speech disorder, a notable feature was its big stretch of consecutive glutamine (Q) residues, the longest polyQ tract in a native protein. @shadys11.bsky.social et al here use it as a model to reveal how polyQ proteins avoid forming toxic assemblies.🙌🧪
DNA binding and mitotic phosphorylation protect polyglutamine proteins from assembly formation
DNA binding and phosphorylation protect FOXP2, a transcription factor with the longest
polyQ track in the proteome, from aggregation during interphase and mitosis. Harnessing
these native solubility-p...
www.cell.com
April 22, 2025 at 1:06 PM
When we first isolated FOXP2 & implicated it in speech disorder, a notable feature was its big stretch of consecutive glutamine (Q) residues, the longest polyQ tract in a native protein. @shadys11.bsky.social et al here use it as a model to reveal how polyQ proteins avoid forming toxic assemblies.🙌🧪
Online now! Online now! Distinct autophagy impairment mechanisms of huntingtin aggregates with different polyQ lengths #chembiol
Distinct autophagy impairment mechanisms of huntingtin aggregates with different polyQ lengths
PolyQ expansion drives pathological heterogeneity in Huntington’s disease. Kim et al. show polyQ103 evades p62 recognition, while bulky polyQ-p62 complexes hinder autophagosome maturation. They also demonstrate that optineurin selectively promotes autophagic clearance of K63-ubiquitinated Q103 aggregates, suggesting a polyQ length-dependent therapeutic strategy.
dlvr.it
April 13, 2026 at 3:31 PM
Online now! Online now! Distinct autophagy impairment mechanisms of huntingtin aggregates with different polyQ lengths #chembiol
I am incredibly proud to share that my work has officially been published in Cell! @cp-cell.bsky.social
This work was a product of years of dedication and countless hours of research in the labs of Joanna Wysocka and Dan Jarosz labs @stanfordmedicine.bsky.social
www.cell.com/cell/fulltex...
This work was a product of years of dedication and countless hours of research in the labs of Joanna Wysocka and Dan Jarosz labs @stanfordmedicine.bsky.social
www.cell.com/cell/fulltex...
DNA binding and mitotic phosphorylation protect polyglutamine proteins from assembly formation
DNA binding and phosphorylation protect FOXP2, a transcription factor with the longest
polyQ track in the proteome, from aggregation during interphase and mitosis. Harnessing
these native solubility-p...
www.cell.com
April 21, 2025 at 12:01 PM
I am incredibly proud to share that my work has officially been published in Cell! @cp-cell.bsky.social
This work was a product of years of dedication and countless hours of research in the labs of Joanna Wysocka and Dan Jarosz labs @stanfordmedicine.bsky.social
www.cell.com/cell/fulltex...
This work was a product of years of dedication and countless hours of research in the labs of Joanna Wysocka and Dan Jarosz labs @stanfordmedicine.bsky.social
www.cell.com/cell/fulltex...
End of a busy day of PhD defenses. Congratulations to Dr Raffaella Parlato from my lab! And also to Dr Vasista Adupa from the Onck lab! Two #polyQ containing theses and defenses. :-)
February 17, 2026 at 4:25 PM
End of a busy day of PhD defenses. Congratulations to Dr Raffaella Parlato from my lab! And also to Dr Vasista Adupa from the Onck lab! Two #polyQ containing theses and defenses. :-)
Nice question! Actually, yes a 27 kDa protein (GFP) is visible as a distinct dot in tomograms (even with an old K2 detector). See all the dots decorating PolyQ filaments (green arrowheads, Bäuerlein et al.) and VIPP1-coated membrane tubes (panels O-R, Gupta et al.). The "cell buffer" is smaller! 🧪🧶🧬
January 19, 2025 at 12:43 AM
Nice question! Actually, yes a 27 kDa protein (GFP) is visible as a distinct dot in tomograms (even with an old K2 detector). See all the dots decorating PolyQ filaments (green arrowheads, Bäuerlein et al.) and VIPP1-coated membrane tubes (panels O-R, Gupta et al.). The "cell buffer" is smaller! 🧪🧶🧬
Distinct autophagy impairment mechanisms of huntingtin aggregates with different polyQ lengths
Distinct autophagy impairment mechanisms of huntingtin aggregates with different polyQ lengths
PolyQ expansion drives pathological heterogeneity in Huntington’s disease. Kim et al. show polyQ103 evades p62 recognition, while bulky polyQ-p62 complexes hinder autophagosome maturation. They also demonstrate that optineurin selectively promotes autophagic clearance of K63-ubiquitinated Q103 aggregates, suggesting a polyQ length-dependent therapeutic strategy.
dlvr.it
April 16, 2026 at 7:31 PM
Distinct autophagy impairment mechanisms of huntingtin aggregates with different polyQ lengths
Korsten et al. employ live cell imaging and expansion microscopy to show that nuclear polyQ aggregates associated with #HuntingtonDisease induce nuclear envelope (NE) blebbing and cause NE ruptures. rupress.org/jcb/article/...
📕 In our Intermediate Filaments collection: rupress.org/jcb/collecti...
📕 In our Intermediate Filaments collection: rupress.org/jcb/collecti...
September 27, 2025 at 8:30 AM
Korsten et al. employ live cell imaging and expansion microscopy to show that nuclear polyQ aggregates associated with #HuntingtonDisease induce nuclear envelope (NE) blebbing and cause NE ruptures. rupress.org/jcb/article/...
📕 In our Intermediate Filaments collection: rupress.org/jcb/collecti...
📕 In our Intermediate Filaments collection: rupress.org/jcb/collecti...
Visualization of autophagic structures near solid polyQ aggregates reveals how they undermine autophagy pubmed.ncbi.nlm.nih.gov/40367301/ #cryoem
May 15, 2025 at 1:18 PM
Visualization of autophagic structures near solid polyQ aggregates reveals how they undermine autophagy pubmed.ncbi.nlm.nih.gov/40367301/ #cryoem
Looking forward to #ENCISMAR2025. First ENC since before COVID…. My talk is Thu morning, on our work using integrative structural biology for understanding the structure of polyQ protein aggregates associated with #huntingtonsdisease
See you in Asilomar?
See you in Asilomar?
April 6, 2025 at 1:14 AM
Looking forward to #ENCISMAR2025. First ENC since before COVID…. My talk is Thu morning, on our work using integrative structural biology for understanding the structure of polyQ protein aggregates associated with #huntingtonsdisease
See you in Asilomar?
See you in Asilomar?
In planta expression of human polyQ-expanded huntingtin fragment reveals mechanisms to prevent disease-related protein aggregation
www.nature.com/articles/s43...
#plantscience
www.nature.com/articles/s43...
#plantscience
In planta expression of human polyQ-expanded huntingtin fragment reveals mechanisms to prevent disea...
Unlike animals, plants prevent pathological polyQ aggregation through chloroplast proteostasis. Expression of the chloroplast protein SSP in human cell and nematode models prevents disease-related pro...
www.nature.com
October 2, 2023 at 5:33 PM
In planta expression of human polyQ-expanded huntingtin fragment reveals mechanisms to prevent disease-related protein aggregation
www.nature.com/articles/s43...
#plantscience
www.nature.com/articles/s43...
#plantscience
New #polyQ #preprint from our colleagues in the Onck lab at @zernike-institute.bsky.social : “A two-bead-per-aminoacid coarse-grained MD model with hydrogen bonding (2BPA-HB) to probe DNAJB6b-mediated suppression of #polyglutamine aggregation in #Huntingtonsdisease ” doi.org/10.64898/202...
doi.org
August 28, 2026 at 1:36 PM
New #polyQ #preprint from our colleagues in the Onck lab at @zernike-institute.bsky.social : “A two-bead-per-aminoacid coarse-grained MD model with hydrogen bonding (2BPA-HB) to probe DNAJB6b-mediated suppression of #polyglutamine aggregation in #Huntingtonsdisease ” doi.org/10.64898/202...
What did the two amino acid substitutions in #FOXP2 that occurred uniquely in the human lineage do? 🧪🧬 🧠
Fascinating new @cp-cell.bsky.social study by @shadys11.bsky.social D. Jarosz & J. Wysocka, uncovering a molecular function for these 2 substitutions in promoting the solubility of FOXP2. (1/n)
Fascinating new @cp-cell.bsky.social study by @shadys11.bsky.social D. Jarosz & J. Wysocka, uncovering a molecular function for these 2 substitutions in promoting the solubility of FOXP2. (1/n)
DNA binding and mitotic phosphorylation protect polyglutamine proteins from assembly formation
DNA binding and phosphorylation protect FOXP2, a transcription factor with the longest
polyQ track in the proteome, from aggregation during interphase and mitosis. Harnessing
these native solubility-p...
www.cell.com
April 22, 2025 at 6:44 AM
What did the two amino acid substitutions in #FOXP2 that occurred uniquely in the human lineage do? 🧪🧬 🧠
Fascinating new @cp-cell.bsky.social study by @shadys11.bsky.social D. Jarosz & J. Wysocka, uncovering a molecular function for these 2 substitutions in promoting the solubility of FOXP2. (1/n)
Fascinating new @cp-cell.bsky.social study by @shadys11.bsky.social D. Jarosz & J. Wysocka, uncovering a molecular function for these 2 substitutions in promoting the solubility of FOXP2. (1/n)
"The Hsp40 co-chaperone DNAJC7 modifies polyglutamine but not polyglycine aggregation"
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
The Hsp40 co-chaperone DNAJC7 modifies polyglutamine but not polyglycine aggregation
Polyglutamine (polyQ) diseases, including Huntington’s disease and several spinocerebellar ataxias, are caused by abnormally expanded CAG nucleotide repeats, which encode aggregation-prone polyQ tract...
www.biorxiv.org
August 17, 2025 at 4:28 PM
"The Hsp40 co-chaperone DNAJC7 modifies polyglutamine but not polyglycine aggregation"
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
It was great to have Prof Ashwani Thakur, from IIT Kanpur, present his talk about #amyloid protein deposits in human disease and in plants (where they are ‘functional’). From #polyQ to plant seeds!
Catch him at the amyloid meeting in Hamburg. @landaulabcssb.bsky.social @cssbhamburg.bsky.social
Catch him at the amyloid meeting in Hamburg. @landaulabcssb.bsky.social @cssbhamburg.bsky.social
September 23, 2025 at 10:55 AM
It was great to have Prof Ashwani Thakur, from IIT Kanpur, present his talk about #amyloid protein deposits in human disease and in plants (where they are ‘functional’). From #polyQ to plant seeds!
Catch him at the amyloid meeting in Hamburg. @landaulabcssb.bsky.social @cssbhamburg.bsky.social
Catch him at the amyloid meeting in Hamburg. @landaulabcssb.bsky.social @cssbhamburg.bsky.social
Now online! DNA binding and mitotic phosphorylation protect polyglutamine proteins from assembly formation
DNA binding and mitotic phosphorylation protect polyglutamine proteins from assembly formation
DNA binding and phosphorylation protect FOXP2, a transcription factor with the longest polyQ track in the proteome, from aggregation during interphase and mitosis. Harnessing these native solubility-promoting mechanisms utilized by FOXP2 diminishes aggregation and amyloid formation by the pathological form of Huntingtin polyQ.
dlvr.it
April 16, 2025 at 12:41 PM
Now online! DNA binding and mitotic phosphorylation protect polyglutamine proteins from assembly formation
PolyA/polyQ-mediated conformational rewiring regulates DNA engagement and drives aggregation in the neuronal transcription factor Ascl1 https://www.biorxiv.org/content/10.64898/2026.05.11.724289v1
May 14, 2026 at 12:49 PM
PolyA/polyQ-mediated conformational rewiring regulates DNA engagement and drives aggregation in the neuronal transcription factor Ascl1 https://www.biorxiv.org/content/10.64898/2026.05.11.724289v1
PolyA/polyQ-mediated conformational rewiring regulates DNA engagement and drives aggregation in the neuronal transcription factor Ascl1 https://www.biorxiv.org/content/10.64898/2026.05.11.724289v1
May 14, 2026 at 12:49 PM
PolyA/polyQ-mediated conformational rewiring regulates DNA engagement and drives aggregation in the neuronal transcription factor Ascl1 https://www.biorxiv.org/content/10.64898/2026.05.11.724289v1
In C. elegans & human cells, we found that age-related EPS8/RAC signaling hyperactivation promotes pathological aggregation of fifferent proteins (polyQ, FUS, TDP-43).
Decreasing EPS8 (or tuning RAC signaling) prevents aggregation & and neurodegeneration.
Decreasing EPS8 (or tuning RAC signaling) prevents aggregation & and neurodegeneration.
September 3, 2025 at 9:19 AM
In C. elegans & human cells, we found that age-related EPS8/RAC signaling hyperactivation promotes pathological aggregation of fifferent proteins (polyQ, FUS, TDP-43).
Decreasing EPS8 (or tuning RAC signaling) prevents aggregation & and neurodegeneration.
Decreasing EPS8 (or tuning RAC signaling) prevents aggregation & and neurodegeneration.
Even my polyq!au with MediaBelle and my lil staticbelle fankid oc lol Vaggi gets to be badass stepmom and this kid has quite the crazy bunch looking out for them lol
June 12, 2026 at 8:21 PM
Even my polyq!au with MediaBelle and my lil staticbelle fankid oc lol Vaggi gets to be badass stepmom and this kid has quite the crazy bunch looking out for them lol
Dubey, S. K., Lloyd, T. E., Tapadia, M. G. (2024). Disrupted nuclear import of cell cycle proteins in Huntington's/PolyQ disease causes neurodevelopment defects in cellular and #Drosophila model. Heliyon, 10(4):e26393 www.cell.com/heliyon/full...
Disrupted nuclear import of cell cycle proteins in Huntington's/PolyQ disease causes neurodevelopment defects in cellular and Drosophila model
Huntington's disease is caused by an expansion of CAG repeats in exon 1 of the huntingtin
gene encoding an extended PolyQ tract within the Huntingtin protein (mHtt). This expansion
results in selectiv...
www.cell.com
October 16, 2024 at 5:23 PM
Dubey, S. K., Lloyd, T. E., Tapadia, M. G. (2024). Disrupted nuclear import of cell cycle proteins in Huntington's/PolyQ disease causes neurodevelopment defects in cellular and #Drosophila model. Heliyon, 10(4):e26393 www.cell.com/heliyon/full...
Thanks for including us Ben and all. If anyone has an ataxia patient with a EP400 polyQ expansion we'd love to hear from you. #repeatome #raredisease #ataxia
It was great to be able to contribute the EP400 finding to this preprint. Together with @ginaravenscroft.bsky.social and @cfolland.bsky.social we flagged a novel CAG repeat locus in the EP400 gene as a likely (though extremely rare) cause of spinocerebellar ataxia when expanded to ≥55 repeats. [1/N]
Detailed tandem repeat allele profiling in 1,027 long-read genomes reveals genome-wide patterns of pathogenicity https://www.biorxiv.org/content/10.1101/2025.01.06.631535v1
January 10, 2025 at 3:22 AM
Thanks for including us Ben and all. If anyone has an ataxia patient with a EP400 polyQ expansion we'd love to hear from you. #repeatome #raredisease #ataxia
Now available at the journal: Integrative determination of atomic structure of mutant huntingtin exon 1 fibrils implicated in Huntington disease
doi.org/10.1038/s414...
#polyq #amyloid
doi.org/10.1038/s414...
#polyq #amyloid
Integrative determination of atomic structure of mutant huntingtin exon 1 fibrils implicated in Huntington disease - Nature Communications
An integrated structural biology approach encompassing solid-state NMR and molecular dynamics simulations was implemented to obtain an atomic view of the ordered polyglutamine core and fuzzy coat of t...
doi.org
December 30, 2024 at 8:11 PM
Now available at the journal: Integrative determination of atomic structure of mutant huntingtin exon 1 fibrils implicated in Huntington disease
doi.org/10.1038/s414...
#polyq #amyloid
doi.org/10.1038/s414...
#polyq #amyloid
🚨Plugin Alert🚨 Laszlo Dobrovolszki has released ‘PolyQuad’ on iOS!!
PolyQuad is one synthesizer built from four complete voices — and the instrument is what they make together. Available NOW in the App Store!!
apps.apple.com/us/app/polyq...
PolyQuad is one synthesizer built from four complete voices — and the instrument is what they make together. Available NOW in the App Store!!
apps.apple.com/us/app/polyq...
September 7, 2026 at 6:42 AM
🚨Plugin Alert🚨 Laszlo Dobrovolszki has released ‘PolyQuad’ on iOS!!
PolyQuad is one synthesizer built from four complete voices — and the instrument is what they make together. Available NOW in the App Store!!
apps.apple.com/us/app/polyq...
PolyQuad is one synthesizer built from four complete voices — and the instrument is what they make together. Available NOW in the App Store!!
apps.apple.com/us/app/polyq...
SCA1 is a neurodegenerative disease driven by polyQ expansion in ATXN1
doi.org/10.1172/JCI1...
@limlabyale.bsky.social & team provide strong evidence on the role of oligodendrocyte-specific expression of pathogenic ATXN1 in neuronal malfunction and systemic dysfunction in mouse models.
doi.org/10.1172/JCI1...
@limlabyale.bsky.social & team provide strong evidence on the role of oligodendrocyte-specific expression of pathogenic ATXN1 in neuronal malfunction and systemic dysfunction in mouse models.
June 16, 2026 at 12:24 PM
SCA1 is a neurodegenerative disease driven by polyQ expansion in ATXN1
doi.org/10.1172/JCI1...
@limlabyale.bsky.social & team provide strong evidence on the role of oligodendrocyte-specific expression of pathogenic ATXN1 in neuronal malfunction and systemic dysfunction in mouse models.
doi.org/10.1172/JCI1...
@limlabyale.bsky.social & team provide strong evidence on the role of oligodendrocyte-specific expression of pathogenic ATXN1 in neuronal malfunction and systemic dysfunction in mouse models.
The first model of full length human androgen receptor and its polyQ expanded variant!
onlinelibrary.wiley.com/doi/full/10....
onlinelibrary.wiley.com/doi/full/10....
#endocrinology #androgen #hormone #receptor #SBMA #polyglutamine #prostate
onlinelibrary.wiley.com/doi/full/10....
onlinelibrary.wiley.com/doi/full/10....
#endocrinology #androgen #hormone #receptor #SBMA #polyglutamine #prostate
Polyglutamine expansion induced dynamic misfolding of androgen receptor
Spinal bulbar muscular atrophy (SBMA) is caused by a polyglutamine expansion (pQe) in the N-terminal transactivation domain of the human androgen receptor (AR-NTD), resulting in a combination of toxi...
onlinelibrary.wiley.com
May 15, 2025 at 1:09 PM
The first model of full length human androgen receptor and its polyQ expanded variant!
onlinelibrary.wiley.com/doi/full/10....
onlinelibrary.wiley.com/doi/full/10....
#endocrinology #androgen #hormone #receptor #SBMA #polyglutamine #prostate
onlinelibrary.wiley.com/doi/full/10....
onlinelibrary.wiley.com/doi/full/10....
#endocrinology #androgen #hormone #receptor #SBMA #polyglutamine #prostate