Molecular mechanisms of neuropsychiatric disorders @broadinstitute.
Cambridge, MA
Joined April 2013
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Sameer Aryal retweeted
Neuronal stimulation induces immediate early genes (IEGs) such as Fos. But what about the continuous, spontaneous activity neurons experience most of the time? Does ongoing network activity also shape gene expression? If so, which genes are regulated?
biorxiv.org/content/10.64898…
Sameer Aryal retweeted
This study reports that Srrm2+/- mice exhibit impaired sleep spindle activity. In our recent preprint (biorxiv.org/content/10.64898…) we showed that nuclear speckles/Srrm2 are critical for maintaining network activity integrity in vitro. Exciting to see these findings converge!
Srrm2 haploinsufficiency drives SynGAP-γ reduction, Agap3 mis-splicing, and oligodendrocyte deficits in a genetic mouse model of schizophrenia dlvr.it/TSkFD6
Sameer Aryal retweeted
Srrm2 haploinsufficiency drives SynGAP-γ reduction, Agap3 mis-splicing, and oligodendrocyte deficits in a genetic mouse model of schizophrenia dlvr.it/TSkFD6
Sameer Aryal retweeted
Elevated synaptic PKA activity and abnormal striatal dopamine signaling in Akap11 mutant mice, a genetic model of schizophrenia and ... biorxiv.org/cgi/content/shor… #biorxiv_neursci
Sameer Aryal retweeted
Akap11 mutations greatly increase risk for #bipolar disorder and #schizophrenia. Not much was known about this gene when we started. Here’s what we learned!
biorxiv.org/content/10.1101/…
Thanks to Morgan Sheng, @ajgrange, Yang Ge, Borislav Dejanovic & crew @broadinstitute
Sameer Aryal retweeted
Excited to share that our paper on cell-type specific changes in the striatal medium spiny neurons underlying the expression of RRBs in FXS mice is finally online @CellReports. Thanks to team members from @KlannLab, @CarterAG, @NicTritsch, and @BagniLab for their contribution!1/6
Thrilled to share @fran_longo17's latest work describing cell type-specific disruption of striatal circuitry in FXS. Many thanks to our collaborators in the labs of @CarterAG, @BagniLab, & @NicTritsch - sometimes it takes a village! sciencedirect.com/science/ar…
Sameer Aryal retweeted
Nat Biotech recently published a provocative study claiming single synapse RNA-seq. Unfortunately, there is no evidence demonstrating droplet-based sequencing of single synaptosomes. They are likely studying random pieces of cellular debris. Our reply:
nature.com/articles/s41587-0…
Sameer Aryal retweeted
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@_sameeraryal shows shared molecular changes in schizophrenia and bipolar disorder, offering new possibilities for understanding and treating these disorders!#MentalHealth #Schizophrenia #BipolarDisorder 🧠💡
👉 rdcu.be/dhoxC
Sameer Aryal retweeted
A deep, unbiased analysis of synapse proteins in brain tissue from individuals with schizophrenia, those with bipolar disorder, and unaffected individuals uncovers molecular evidence that these disorders have more in common than previously thought. broad.io/SynapseProteomics
Pleased to note that this study is now published in the open-access journal @CellReports!
Deep proteomics identifies shared molecular pathway alterations in synapses of patients with schizophrenia and bipolar disorder and mouse model dlvr.it/SnvVg0
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Happy to share two recent studies I contributed to. The first led by @fran_longo17 found that cell-type-specific disruption of cortico-striatal circuitry drives repetitive patterns of behavior in fragile X syndrome model mice.
Excited to share our last work from @KlannLab where we unveiled cell-type specific changes in the striatal medium spiny neurons underlying the expression of RRBs in FXS mice! A great collaboration with @CarterAG, @NicTritsch, and @BagniClaudia labs! 1/5
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The second study, using transcriptomic and proteomic approaches, found brain region-specific changes in neurons and glia and dysregulation of dopamine signaling in Grin2a mutant mice—a schizophrenia mouse model with bona-fide human genetic validity.
xitter.gq/biorxiv_neursci/status…
Brain region-specific changes in neurons and glia and dysregulation of dopamine signaling in Grin2a mutant mice biorxiv.org/cgi/content/shor… #biorxiv_neursci
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Sameer Aryal retweeted
Spatially Resolved Single-cell Translatomics at Molecular Resolution biorxiv.org/cgi/content/shor… #bioRxiv
Sameer Aryal retweeted
Deep proteomics identifies shared molecular pathway alterations in synapses of schizophrenia and bipolar disorder patients and mouse model biorxiv.org/cgi/content/shor… #bioRxiv
We carried out proteomics of synaptic fractions purified from the DLPFC of humans with schizophrenia and bipolar disorder. We found multiple interesting changes, some of which were also seen in mice lacking Akap11, a shared risk gene for both diseases. Happy to share the work!
Deep proteomics identifies shared molecular pathway alterations in synapses of schizophrenia and bipolar disorder patients and mouse ... biorxiv.org/cgi/content/shor… #biorxiv_neursci
Sameer Aryal retweeted
On behalf of the Bipolar Exome (BipEx) project, I'm excited to present our analyses of exome sequencing data from 13,933 bipolar disorder cases and 14,422 controls which highlights AKAP11 as a shared risk gene with schizophrenia: medrxiv.org/cgi/content/shor… (1/9)
Sameer Aryal retweeted
At long last, I am pleased to say that the SCHEMA consortium’s paper has been published online in @Nature (nature.com/articles/s41586-0…): analysis of >120K individuals shows that rare coding variants in 10 genes confer substantial risk for schizophrenia. (1/6)
ALT Genetic architecture of schizophrenia
Very informative summary of rare variants of large effect size across phenotypes and diseases.
Everyone loves a genetic association with a large effect size (particularly when it's protective). But it's not easy to find one.
Here I list few studies I read in 2021 that identified large effect rare variant associations leading to beautiful gene discoveries. 🧵
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Recent work has uncovered ultra rare gene disrupting variants that greatly increase schizophrenia risk (see schema.broadinstitute.org). Insights from such studies have reshaped our understanding of neuropsychiatric disease.