Yin Shen, PhD

Assistant Professor
Department of Neurology
Institute for Human Genetics
Research Overview: 

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.

  1. 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.
  2. 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.
  3. 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.
Primary Thematic Area: 
Human Genetics
Secondary Thematic Area: 
Developmental & Stem Cell Biology
Research Summary: 
Functional genomics, gene regulation, 3D chromatin architecture, and human diseases

Websites

Publications: 

An atlas of dynamic chromatin landscapes in mouse fetal development.

Nature

Gorkin DU, Barozzi I, Zhao Y, Zhang Y, Huang H, Lee AY, Li B, Chiou J, Wildberg A, Ding B, Zhang B, Wang M, Strattan JS, Davidson JM, Qiu Y, Afzal V, Akiyama JA, Plajzer-Frick I, Novak CS, Kato M, Garvin TH, Pham QT, Harrington AN, Mannion BJ, Lee EA, Fukuda-Yuzawa Y, He Y, Preissl S, Chee S, Han JY, Williams BA, Trout D, Amrhein H, Yang H, Cherry JM, Wang W, Gaulton K, Ecker JR, Shen Y, Dickel DE, Visel A, Pennacchio LA, Ren B

SMART-Q:  An Integrative Pipeline Quantifying Cell Type-Specific RNA Transcription.

PloS one

Yang X, Bergenholtz S, Maliskova L, Pebworth MP, Kriegstein AR, Li Y, Shen Y

SAME-clustering: Single-cell Aggregated Clustering via Mixture Model Ensemble.

Nucleic acids research

Huh R, Yang Y, Jiang Y, Shen Y, Li Y

Mapping cis-regulatory chromatin contacts in neural cells links neuropsychiatric disorder risk variants to target genes.

Nature genetics

Song M, Yang X, Ren X, Maliskova L, Li B, Jones IR, Wang C, Jacob F, Wu K, Traglia M, Tam TW, Jamieson K, Lu SY, Ming GL, Li Y, Yao J, Weiss LA, Dixon JR, Judge LM, Conklin BR, Song H, Gan L, Shen Y