
Assistant Professor
Department of Neurology
Institute for Human Genetics
We are a functional genomics lab interested in investigating fundamental mechanisms of transcriptional control underlying cellular function. We utilize human pluripotent stem cells to model development and diseases as well as innovative genomic and genetic tools to investigate how regulatory elements affect gene expression. Specifically, we focus on elucidating the causal relationship between genetic and epigenetic variations in regulatory sequences (e.g., enhancers) in the context of development and diseases, and how these factors interplay to control gene regulation in mammalian cells.
- Functional genomics (the ENCODE project): high-throughput CRISPR/Cas9 screening of functional regulatory elements.
We are using high-throughput CRISPR/Cas9-mediated genetic screening to interrogate the biological significance of a large number of non-coding regulatory sequences in the mammalian genome in both embryonic stem cells and iPSC-derived neural cell types. - Charting the regulatory landscape of human brain development and function.
We are utilizing integrative, unbiased, and high-throughput genomic and genetic tools (ATAC-seq, RNA-seq, ChIP-seq, 4C-seq, Hi-C, and CRISPR) to identify and functionally characterize cis-regulatory elements in human brain cells. - Investigating the functions of non-coding genetic variation associated with neurological diseases.
Putative regulatory regions harbor a disproportionately large number of sequence variants associated with human traits and diseases, leading to the notion that genetic lesions in the cis-regulatory elements contribute substantially to common human diseases. We are using functional genomics tools to investigate how non-coding variants associated with complex neurological disorders (e.g., autism spectrum disorders (ASD), Alzheimer diseases (AD), and Parkinson disease (PD)) contribute to disease.
Research Summary
Functional genomics, gene regulation, 3D chromatin architecture, and human diseases
Websites
Publications
Opportunities and challenges of single-cell and spatially resolved genomics methods for neuroscience discovery.
Nature neuroscience
Author Correction: MYC phase separation selectively modulates the transcriptome.
Nature structural & molecular biology
Combinatorial transcription factor binding encodes cis-regulatory wiring of mouse forebrain GABAergic neurogenesis.
Developmental cell
The PRC2.1 Subcomplex Opposes G1 Progression through Regulation of CCND1 and CCND2.
bioRxiv : the preprint server for biology
CRISPR tiling deletion screens reveal functional enhancers of neuropsychiatric risk genes and allelic compensation effects (ACE) on transcription.
bioRxiv : the preprint server for biology
Widespread transposable element dysregulation in human aging brains with Alzheimer's disease.
Alzheimer's & dementia : the journal of the Alzheimer's Association
Systematic assessment of long-read RNA-seq methods for transcript identification and quantification.
Nature methods
MYC phase separation selectively modulates the transcriptome.
Nature structural & molecular biology
Deconvolution of polygenic risk score in single cells unravels cellular and molecular heterogeneity of complex human diseases.
bioRxiv : the preprint server for biology
A conserved molecular logic for neurogenesis to gliogenesis switch in the cerebral cortex.
Proceedings of the National Academy of Sciences of the United States of America
Phase separation of YAP-MAML2 differentially regulates the transcriptome.
Proceedings of the National Academy of Sciences of the United States of America
High-throughput PRIME-editing screens identify functional DNA variants in the human genome.
Molecular cell
High-throughput CRISPRi and CRISPRa technologies in 3D genome regulation for neuropsychiatric diseases.
Human molecular genetics
Genetically encoded chemical crosslinking of RNA in vivo.
Nature chemistry
Dual genome-wide coding and lncRNA screens in neural induction of induced pluripotent stem cells.
Cell genomics
Coordinated transcriptional and catabolic programs support iron dependent adaptation to RAS-MAPK pathway inhibition in pancreatic cancer.
Cancer discovery
THUNDER: A reference-free deconvolution method to infer cell type proportions from bulk Hi-C data.
PLoS genetics
Transcriptional network orchestrating regional patterning of cortical progenitors.
Proceedings of the National Academy of Sciences of the United States of America
Parallel characterization of cis-regulatory elements for multiple genes using CRISPRpath.
Science advances
SMNN: batch effect correction for single-cell RNA-seq data via supervised mutual nearest neighbor detection.
Briefings in Bioinformatics
Deletion of CTCF sites in the SHH locus alters enhancer-promoter interactions and leads to acheiropodia.
Nature communications
The C. elegans homolog of human panic-disorder risk gene TMEM132D orchestrates neuronal morphogenesis through the WAVE-regulatory complex.
Molecular brain
SAME-clustering: Single-cell Aggregated Clustering via Mixture Model Ensemble.
Nucleic acids research
Mapping cis-regulatory chromatin contacts in neural cells links neuropsychiatric disorder risk variants to target genes.
Nature genetics
Proximal recolonization by self-renewing microglia re-establishes microglial homeostasis in the adult mouse brain.
PLoS biology
Gene regulation in the 3D genome.
Human molecular genetics
A tiling-deletion-based genetic screen for cis-regulatory element identification in mammalian cells.
Nature methods
Improved regulatory element prediction based on tissue-specific local epigenomic signatures.
Proceedings of the National Academy of Sciences of the United States of America
A new class of temporarily phenotypic enhancers identified by CRISPR/Cas9-mediated genetic screening.
Genome research
A panel of CpG methylation sites distinguishes human embryonic stem cells and induced pluripotent stem cells.
Stem cell reports
Epigenetic memory at embryonic enhancers identified in DNA methylation maps from adult mouse tissues.
Nature genetics
An encyclopedia of mouse DNA elements (Mouse ENCODE).
Genome biology
Polycomb-like 3 promotes polycomb repressive complex 2 binding to CpG islands and embryonic stem cell self-renewal.
PLoS genetics
Functional modules distinguish human induced pluripotent stem cells from embryonic stem cells.
Stem cells and development
Genome-wide DNA methylation profiling: the mDIP-chip technology.
Methods in molecular biology (Clifton, N.J.)
X-inactivation in female human embryonic stem cells is in a nonrandom pattern and prone to epigenetic alterations.
Proceedings of the National Academy of Sciences of the United States of America
Abnormal CpG island methylation occurs during in vitro differentiation of human embryonic stem cells.
Human molecular genetics
DNA methylation controls the timing of astrogliogenesis through regulation of JAK-STAT signaling.
Development (Cambridge, England)