Nael Nadif Kasri

Navigating Human Astrocyte Differentiation: Direct and Rapid one-step Differentiation of Induced Pluripotent Stem Cells to Functional Astrocytes Supporting Neuronal Network development

This study presents a one-step protocol to differentiate hiPSCs into functional astrocytes, enabling co-culture with neurons to support network development.

Maturation-dependent splicing alterations constrain SYNGAP1 splice-switching therapy

The paper shows that SYNGAP1 splice-switching therapy may be ineffective in mature neurons due to reduced A3SS transcript abundance.

Dissecting the sources of variation in neuronally differentiated iPSC lines through multi-omics analysis

The paper identifies major sources of variability in iPSC-derived neurons and shows how correcting these improves disease signature detection.

KG-Bench: Benchmarking Graph Neural Network Algorithms for Drug Repurposing

KG-Bench benchmarks graph neural networks for drug repurposing using the Open Targets dataset, finding TransformerConv achieves the highest performance.

Integrative transcriptomics and electrophysiological profiling of hiPSC-derived neurons identifies novel druggable pathways in Koolen-de Vries Syndrome

MEA-LINK identifies the CCL4-CCR5 axis in neuronal hyperactivity control by human microglia

MEA-LINK identifies CCL4-CCR5 signaling as a mechanism by which human microglia regulate neuronal hyperactivity through secreted factors and network activity.

Mapping NMD-coupled alternative splicing in iPSC-derived brain cells: a resource for therapeutic discovery

The paper maps NMD-coupled alternative splicing events in iPSC-derived brain cells and identifies therapeutic targets for neurodevelopmental disorders.

Evolutionary hotspots of structural variation drive inter-individual differences in the expression of fusion transcripts in the human brain

The paper identifies fusion transcripts in human brain tissues, showing they are enriched in segmental duplication hotspots and contribute to inter-individual expression differences.

Long-term co-maturation of stem cell-derived microglia and neuronal networks: an optimized platform to assess human microglial contribution to neuronal function

This paper develops a co-maturation protocol to study human microglia-neuron interactions using hiPSCs, showing astrocytes are needed for microglia survival and integration into neuronal networks.

Targeting AASS improves neurotoxicity and mitochondrial function in astrocyte models for pyridoxine dependent epilepsy

This study shows that targeting AASS in astrocytes reduces neurotoxicity and improves mitochondrial function in a model of pyridoxine-dependent epilepsy.

Whole-brain clearing reveals region- and cell type-specific imbalances in inhibitory neurons in a mouse model for Kleefstra Syndrome

The paper uses whole-brain clearing and imaging to identify region- and cell type-specific changes in GABAergic neurons in a mouse model of Kleefstra Syndrome.

The Neuronal Primary Cilium is a Key Regulator of Homeostatic Plasticity

This study identifies primary cilia as regulators of neuronal homeostatic plasticity, showing they dynamically change volume in response to activity levels and that ciliary dysfunction impairs multiple aspects of homeostasis.

THE NSL COMPLEX PROMOTES NEURAL DEVELOPMENT BY PREVENTING R-LOOP INDUCED REPLICATION STRESS

This study shows the NSL complex prevents R-loop induced replication stress during neural development, leading to developmental abnormalities when disrupted.

Systematic analysis of genetic and phenotypic characteristics reveals antisense oligonucleotide therapy potential for one-third of neurodevelopmental disorders

The paper evaluates the suitability of antisense oligonucleotide therapy for neurodevelopmental disorders by analyzing genetic and phenotypic characteristics, identifying 38% of disorders as potentially targetable.

Human-Specific Regulation of CHD2 Controls the Tempo of Cortical Development through Lysosomal Homeostasis

This study identifies a human-specific CHD2 regulatory variant that influences cortical development tempo via lysosomal homeostasis, showing therapeutic potential through lysosomal restoration.

CACNA1A haploinsufficiency leads to reduced synaptic function and increased intrinsic excitability

This study characterizes a human neuronal model of CACNA1A haploinsufficiency, revealing synaptic deficits and increased intrinsic excitability linked to reduced potassium channel function.

Neuronal autophagosomes are transported to astrocytes for degradation

The paper identifies a novel pathway where astrocytes clear pre-synaptic autophagosomes from neurons through a cholesterol-dependent endocytosis process without requiring direct cell contact or retrograde transport.

Rapid specification of human pluripotent stem cells to functional astrocytes

This study develops a method to differentiate human pluripotent stem cells into functional astrocytes in 28 days, validated by marker expression and network activity support.

A human in vitro neuronal model for studying homeostatic plasticity at the network level

This study uses human iPSC-derived neuronal networks to show that homeostatic plasticity involves network re-arrangement, increased excitability, and changes in gene expression related to extracellular matrix and cell communication.

SCN1A-deficient hiPSC-derived excitatory neuronal networks display mutation-specific phenotypes

This study investigates SCN1A mutations in excitatory neuronal networks derived from patient hiPSCs, revealing mutation-specific phenotypes that correlate with clinical outcomes and drug responses.

FriendlyClearMap: An optimized toolkit for mouse brain mapping and analysis

FriendlyClearMap simplifies and extends the ClearMap pipeline for mouse brain analysis, enabling efficient and scalable neuroanatomical studies.

7q11.23 CNV alters protein synthesis and REST-mediated neuronal intrinsic excitability

This study investigates how 7q11.23 CNVs affect protein synthesis and neuronal excitability in neurodevelopmental disorders using patient-derived neurons and multi-omics approaches.

Regulation of mitophagy by the NSL complex underlies genetic risk for Parkinson's disease at Chr16q11.2 and on the MAPT H1 allele

The paper identifies KAT8 and KANSL1 as regulators of PINK1-mitophagy linked to Parkinson's disease risk, suggesting a novel pathway for therapeutic targeting.

Loss-of-function variants in the schizophrenia risk gene SETD1A alter neuronal network activity in human neurons through cAMP/PKA pathway

This study shows that SETD1A loss-of-function mutations increase dendritic complexity and neuronal bursting in human neurons via a hyperactive cAMP/PKA pathway, which can be rescued by pharmacological intervention.

Sonlicromanol improves neuronal network dysfunction and transcriptome changes linked to m.3243A > G heteroplasmy in iPSC-derived neurons

Human neuronal networks on micro-electrode arrays are a highly robust tool to study disease-specific genotype-phenotype correlations in vitro

The paper benchmarks MEA recordings from healthy hiPSC-derived neuronal networks to establish standards for experimental design and analysis, showing MEAs are robust for disease-phenotyping and drug discovery.

KANSL1 Deficiency Causes Neuronal Dysfunction by Oxidative Stress-Induced Autophagy

This study shows that KANSL1 deficiency leads to oxidative stress-induced autophagy, causing synaptic dysfunction and neuronal network impairments in neurons.

Cadherin-13 is a critical regulator of GABAergic modulation in human stem cell derived neuronal networks

This study investigates the role of CDH13 in regulating GABAergic inhibition in human-derived neuronal networks and shows its impact on E/I balance.

KMT2D haploinsufficiency in Kabuki Syndrome disrupts neuronal function through transcriptional and chromatin rewiring independent of H3K4-monomethylation

This study investigates how KMT2D mutations in Kabuki Syndrome disrupt neuronal function through chromatin and transcriptional changes, independent of H3K4me1.

Ngn2 induces diverse neuronal lineages from human pluripotency

This study uses single-cell transcriptomics to show that Ngn2 overexpression in human iPSCs generates heterogeneous neurons, including peripheral nervous system-like populations, and that Ngn2 dosage affects neuron fate.