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Selected publications

For the complete list of publications, see here


We analyzed >700,000 single-nucleus RNA sequencing profiles from 106 donors during prenatal and postnatal developmental stages and identified lineage-specific programs that underlie the development of specific subtypes of excitatory cortical neurons, interneurons, glial cell types, and brain vasculature. By leveraging single-nucleus chromatin accessibility data, we delineated enhancer gene regulatory networks and transcription factors that control commitment of specific cortical lineages. By intersecting our results with genetic risk factors for human brain diseases, we identified the cortical cell types and lineages most vulnerable to genetic insults of different brain disorders, especially autism. We find that lineage-specific gene expression programs up-regulated in female cells are especially enriched for the genetic risk factors of autism. Our study captures the molecular progression of cortical lineages across human development.


This paper utilized single-nucleus RNA sequencing of post-mortem brain tissue samples from ASD patients to identify cell type-specific transcriptomics changes. It demonstrated that upper-layer cortical projection neurons are enriched for ASD-associated gene expression changes, suggesting these neurons are one of the key cell types affected in ASD. The majority of changes we observed were divergent with changes in epilepsy, suggesting they represent core ASD-associated molecular changes. Moreover, changes in upper-layer neurons and microglia were predictive of ASD severity, pointing to their functional role in the disorder. These data highlight most affected neuronal and glial cell types that may be key for therapeutic interventions.


This study combined single-cell genomics and spatial transcriptomics to investigate how specific neuronal and glial cell types are affected in cortical multiple sclerosis lesions. We found that upper-layer cortical projection neurons are especially vulnerable in grey-matter lesions, which might be attributed to subpial inflammation mediated by B cells. We demonstrate that neuronal degeneration progresses as lesions transition from acute to chronic. These data provide insight into cell type-specific mechanisms of pathology of MS and suggests that therapy directed to B cells may be beneficial for treatment of chronic MS lesions.


We utilized single-nucleus RNA sequencing combined with functional assays to investigate cell and molecular dynamics of frontotemporal dementia (FTD), one of the most common causes of dementia. We found that in the progranulin mouse model of FTD, microglial proliferation and activation in the thalamus precedes neuronal pathology and death. Moreover, we found that microglia mediate a pathological response in specific thalamic excitatory neuron subtypes via activation of the complement cascade. In addition to the microglia, astrocytes also change their molecular state during the pathogenesis of FTD, potentially contributing to the neuronal pathology. Our study provided new insights into the cellular and molecular mechanisms of FTD caused by mutations in the progranulin gene.


In this study, we performed a meta-analysis of RNA sequencing data from collected from post-mortem brain tissue of autism spectrum disorder (ASD) patients and controls. These data were generated from different patient cohorts and brain regions, but our analysis demonstrated that ASD-associated gene expression changes converge on common genes and pathway across patients and brain regions. This convergence could be observed both on the level of gene expression and alternative splicing changes. These results, together with previous studies, highlight the remarkable convergence of ASD molecular pathology despite the genetic and clinical heterogeneity of the disease.


We developed a bioinformatics approach to mine public transcript databases to identify non-coding RNAs that are in the antisense orientation of known ASD-assocaited gene loci. We discovered that a number of ASD-associated genes have one or more non-coding antisense transcripts and thus represent complex genomic loci. One such non-coding antisense RNA, SYNGAP1-AS, is unregulated in the brain of ASD patients compared to controls, and the expression of this antisense RNA is negatively correlated with that of its sense counterpart, ASD-associated synaptic gene SYNGAP1. Our data suggests that mutations causing ASD may do so in complex ways, including by affecting the expression and function of regulatory non-coding RNAs.

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