Scott H. Soderling
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View article: Genetic and environmental influences in autism: guiding the future of tailored early detection and intervention
Genetic and environmental influences in autism: guiding the future of tailored early detection and intervention Open
View article: Protein Language Model–Aligned Spectra Embeddings for <i>De Novo</i> Peptide Sequencing
Protein Language Model–Aligned Spectra Embeddings for <i>De Novo</i> Peptide Sequencing Open
We consider the problem of de novo peptide sequencing in tandem mass spectrometry, where the goal is to predict the underlying peptide sequence given a spectrum’s fragment peaks and precursor information. We present PLMNovo, a constrained …
View article: PD-linked LRRK2 G2019S mutation impairs astrocyte morphology and synapse maintenance via ERM hyperphosphorylation
PD-linked LRRK2 G2019S mutation impairs astrocyte morphology and synapse maintenance via ERM hyperphosphorylation Open
Astrocytes are highly complex cells that mediate critical roles in synapse formation and maintenance by establishing thousands of direct contacts with synapses through their perisynaptic processes. Here, we found that the most common Parki…
View article: PD-linked LRRK2 G2019S mutation impairs astrocyte morphology and synapse maintenance via ERM hyperphosphorylation
PD-linked LRRK2 G2019S mutation impairs astrocyte morphology and synapse maintenance via ERM hyperphosphorylation Open
Astrocytes are highly complex cells that mediate critical roles in synapse formation and maintenance by establishing thousands of direct contacts with synapses through their perisynaptic processes. Here, we found that the most common Parki…
View article: Identification of New Ciliary Signaling Pathways in the Brain and Insights into Neurological Disorders
Identification of New Ciliary Signaling Pathways in the Brain and Insights into Neurological Disorders Open
Primary cilia are conserved sensory hubs essential for signaling transduction and embryonic development. Ciliary dysfunction causes a variety of developmental syndromes with neurological features and cognitive impairment whose basis mostly…
View article: Deep Learning-coupled Proximity Proteomics to Deconvolve Kinase Signaling In Vivo
Deep Learning-coupled Proximity Proteomics to Deconvolve Kinase Signaling In Vivo Open
Deconvolving the substrates of hundreds of kinases linked to phosphorylation networks driving cellular behavior is a fundamental, unresolved biological challenge, largely due to the poorly understood interplay of kinase selectivity and sub…
View article: De novo design of peptide binders to conformationally diverse targets with contrastive language modeling
De novo design of peptide binders to conformationally diverse targets with contrastive language modeling Open
Designing binders to target undruggable proteins presents a formidable challenge in drug discovery. In this work, we provide an algorithmic framework to design short, target-binding linear peptides, requiring only the amino acid sequence o…
View article: The Epilepsy–Aphasia Syndrome Gene, Cnksr2, Plays a Critical Role in the Anterior Cingulate Cortex Mediating Vocal Communication
The Epilepsy–Aphasia Syndrome Gene, Cnksr2, Plays a Critical Role in the Anterior Cingulate Cortex Mediating Vocal Communication Open
Epilepsy–aphasia syndrome (EAS) is a spectrum of childhood disorders that exhibit complex comorbidities that include epilepsy and the emergence of cognitive and language disorders. CNKSR2 is an X-linked gene in which mutations are linked t…
View article: Miniaturizing, Modifying, and Magnifying Nature’s Proteins with Raygun
Miniaturizing, Modifying, and Magnifying Nature’s Proteins with Raygun Open
Proteins have evolved over billions of years through extensive and coordinated substitutions, insertions and deletions (indels). Computational protein design cannot yet fully mimic nature’s ability to engineer new proteins from existing te…
View article: Proximity analysis of native proteomes reveals phenotypic modifiers in a mouse model of autism and related neurodevelopmental conditions
Proximity analysis of native proteomes reveals phenotypic modifiers in a mouse model of autism and related neurodevelopmental conditions Open
One of the main drivers of autism spectrum disorder is risk alleles within hundreds of genes, which may interact within shared but unknown protein complexes. Here we develop a scalable genome-editing-mediated approach to target 14 high-con…
View article: Presynaptic Rac1 in the hippocampus selectively regulates working memory
Presynaptic Rac1 in the hippocampus selectively regulates working memory Open
One of the most extensively studied members of the Ras superfamily of small GTPases, Rac1 is an intracellular signal transducer that remodels actin and phosphorylation signaling networks. Previous studies have shown that Rac1-mediated sign…
View article: Presynaptic Rac1 in the hippocampus selectively regulates working memory
Presynaptic Rac1 in the hippocampus selectively regulates working memory Open
One of the most extensively studied members of the Ras superfamily of small GTPases, Rac1 is an intracellular signal transducer that remodels actin and phosphorylation signaling networks. Previous studies have shown that Rac1-mediated sign…
View article: Presynaptic Rac1 in the hippocampus selectively regulates working memory
Presynaptic Rac1 in the hippocampus selectively regulates working memory Open
One of the most extensively studied members of the Ras superfamily of small GTPases, Rac1 is an intracellular signal transducer that remodels actin and phosphorylation signaling networks. Previous studies have shown that Rac1-mediated sign…
View article: Presynaptic Rac1 in the hippocampus selectively regulates working memory
Presynaptic Rac1 in the hippocampus selectively regulates working memory Open
One of the most extensively studied members of the Ras superfamily of small GTPases, Rac1 is an intracellular signal transducer that remodels actin and phosphorylation signaling networks. Previous studies have shown that Rac1-mediated sign…
View article: Identification of new ciliary signaling pathways in the brain and insights into neurological disorders
Identification of new ciliary signaling pathways in the brain and insights into neurological disorders Open
Primary cilia are conserved sensory hubs essential for signaling transduction and embryonic development. Ciliary dysfunction causes a variety of developmental syndromes with neurological features and cognitive impairment, whose basis mostl…
View article: Training-induced circuit-specific excitatory synaptogenesis in mice is required for effort control
Training-induced circuit-specific excitatory synaptogenesis in mice is required for effort control Open
View article: <i>De Novo</i>Design of Peptide Binders to Conformationally Diverse Targets with Contrastive Language Modeling
<i>De Novo</i>Design of Peptide Binders to Conformationally Diverse Targets with Contrastive Language Modeling Open
Designing binders to target undruggable proteins presents a formidable challenge in drug discovery, requiring innovative approaches to overcome the lack of putative binding sites. Recently, generative models have been trained to design bin…
View article: PD-linked LRRK2 G2019S mutation impairs astrocyte morphology and synapse maintenance via ERM hyperphosphorylation
PD-linked LRRK2 G2019S mutation impairs astrocyte morphology and synapse maintenance via ERM hyperphosphorylation Open
Astrocytes are highly complex cells that mediate critical roles in synapse formation and maintenance by establishing thousands of direct contacts with synapses through their perisynaptic processes. Here, we found that the most common Parki…
View article: A Ventromedial Prefrontal-to-Lateral Entorhinal Cortex Pathway Modulates the Gain of Behavioral Responding During Threat
A Ventromedial Prefrontal-to-Lateral Entorhinal Cortex Pathway Modulates the Gain of Behavioral Responding During Threat Open
View article: Proximity Analysis of Native Proteomes Reveals Interactomes Predictive of Phenotypic Modifiers of Autism and Related Neurodevelopmental Conditions
Proximity Analysis of Native Proteomes Reveals Interactomes Predictive of Phenotypic Modifiers of Autism and Related Neurodevelopmental Conditions Open
One of the main drivers of autism spectrum disorder is risk alleles within hundreds of genes, which may interact within shared but unknown protein complexes. Here we develop a scalable genome-editing-mediated approach to target 14 high-con…
View article: A prefrontal to lateral entorhinal pathway disrupts memory
A prefrontal to lateral entorhinal pathway disrupts memory Open
While the neural circuits underlying memory encoding, storage, and retrieval are well characterized, the circuits that act to disrupt memory are enigmatic. Here we find that silencing a projection from the prefrontal cortex to the lateral …
View article: Action potential-coupled Rho GTPase signaling drives presynaptic plasticity
Action potential-coupled Rho GTPase signaling drives presynaptic plasticity Open
In contrast to their postsynaptic counterparts, the contributions of activity-dependent cytoskeletal signaling to presynaptic plasticity remain controversial and poorly understood. To identify and evaluate these signaling pathways, we cond…
View article: Tripartite synaptomics: Cell-surface proximity labeling in vivo
Tripartite synaptomics: Cell-surface proximity labeling in vivo Open
View article: Author response: Action potential-coupled Rho GTPase signaling drives presynaptic plasticity
Author response: Action potential-coupled Rho GTPase signaling drives presynaptic plasticity Open
View article: Training-Induced Circuit-Specific Excitatory Synaptogenesis is Required for Effort Control
Training-Induced Circuit-Specific Excitatory Synaptogenesis is Required for Effort Control Open
Summary Synaptogenesis is essential for circuit development; however, it is unknown whether it is critical for the establishment and performance of goal-directed voluntary behaviors. Here, we show that operant-conditioning via lever-press …
View article: Genetic disruption of WASHC4 drives endo-lysosomal dysfunction and cognitive-movement impairments in mice and humans
Genetic disruption of WASHC4 drives endo-lysosomal dysfunction and cognitive-movement impairments in mice and humans Open
Mutation of the Wiskott–Aldrich syndrome protein and SCAR homology (WASH) complex subunit, SWIP, is implicated in human intellectual disability, but the cellular etiology of this association is unknown. We identify the neuronal WASH comple…
View article: Author response: Genetic disruption of WASHC4 drives endo-lysosomal dysfunction and cognitive-movement impairments in mice and humans
Author response: Genetic disruption of WASHC4 drives endo-lysosomal dysfunction and cognitive-movement impairments in mice and humans Open
Article Figures and data Abstract eLife digest Introduction Results Discussion Materials and methods Data availability References Decision letter Author response Article and author information Metrics Abstract Mutation of the Wiskott–Aldri…
View article: Master Regulators and Cofactors of Human Neuronal Cell Fate Specification Identified by CRISPR Gene Activation Screens
Master Regulators and Cofactors of Human Neuronal Cell Fate Specification Identified by CRISPR Gene Activation Screens Open
View article: Chemico-genetic discovery of astrocytic control of inhibition in vivo
Chemico-genetic discovery of astrocytic control of inhibition in vivo Open
View article: Disruption of Arp2/3 Results in Asymmetric Structural Plasticity of Dendritic Spines and Progressive Synaptic and Behavioral Abnormalities
Disruption of Arp2/3 Results in Asymmetric Structural Plasticity of Dendritic Spines and Progressive Synaptic and Behavioral Abnormalities Open
Despite evidence for a strong genetic contribution to several major psychiatric disorders, individual candidate genes account for only a small fraction of these disorders, leading to the suggestion that multigenetic pathways may be involve…