Yin Shen, PhD

Associate Professor
Department of Neurology
Institute for Human Genetics
Primary Thematic Area
Secondary Thematic Area
Research Summary
Functional genomics, gene regulation, 3D chromatin architecture, and human diseases
Mentorship Development

5/26/20    Effective Strategies for IDPs for Partial Resumption of Lab Research    
9/11/20    Mentoring Across Differences
5/25/21  Sharpening your Mentoring Skills (SyMS) 

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.

Publications

Systematic assessment of long-read RNA-seq methods for transcript identification and quantification.

Nature methods

Pardo-Palacios FJ, Wang D, Reese F, Diekhans M, Carbonell-Sala S, Williams B, Loveland JE, De María M, Adams MS, Balderrama-Gutierrez G, Behera AK, Gonzalez Martinez JM, Hunt T, Lagarde J, Liang CE, Li H, Meade MJ, Moraga Amador DA, Prjibelski AD, Birol I, Bostan H, Brooks AM, Çelik MH, Chen Y, Du MRM, Felton C, Göke J, Hafezqorani S, Herwig R, Kawaji H, Lee J, Li JL, Lienhard M, Mikheenko A, Mulligan D, Nip KM, Pertea M, Ritchie ME, Sim AD, Tang AD, Wan YK, Wang C, Wong BY, Yang C, Barnes I, Berry AE, Capella-Gutierrez S, Cousineau A, Dhillon N, Fernandez-Gonzalez JM, Ferrández-Peral L, Garcia-Reyero N, Götz S, Hernández-Ferrer C, Kondratova L, Liu T, Martinez-Martin A, Menor C, Mestre-Tomás J, Mudge JM, Panayotova NG, Paniagua A, Repchevsky D, Ren X, Rouchka E, Saint-John B, Sapena E, Sheynkman L, Smith ML, Suner MM, Takahashi H, Youngworth IA, Carninci P, Denslow ND, Guigó R, Hunter ME, Maehr R, Shen Y, Tilgner HU, Wold BJ, Vollmers C, Frankish A, Au KF, Sheynkman GM, Mortazavi A, Conesa A, Brooks AN

Multicenter integrated analysis of noncoding CRISPRi screens.

Nature methods

Yao D, Tycko J, Oh JW, Bounds LR, Gosai SJ, Lataniotis L, Mackay-Smith A, Doughty BR, Gabdank I, Schmidt H, Guerrero-Altamirano T, Siklenka K, Guo K, White AD, Youngworth I, Andreeva K, Ren X, Barrera A, Luo Y, Yardimci GG, Tewhey R, Kundaje A, Greenleaf WJ, Sabeti PC, Leslie C, Pritykin Y, Moore JE, Beer MA, Gersbach CA, Reddy TE, Shen Y, Engreitz JM, Bassik MC, Reilly SK

An atlas of gene regulatory elements in adult mouse cerebrum.

Nature

Li YE, Preissl S, Hou X, Zhang Z, Zhang K, Qiu Y, Poirion OB, Li B, Chiou J, Liu H, Pinto-Duarte A, Kubo N, Yang X, Fang R, Wang X, Han JY, Lucero J, Yan Y, Miller M, Kuan S, Gorkin D, Gaulton KJ, Shen Y, Nunn M, Mukamel EA, Behrens MM, Ecker JR, Ren B

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

A comparative encyclopedia of DNA elements in the mouse genome.

Nature

Yue F, Cheng Y, Breschi A, Vierstra J, Wu W, Ryba T, Sandstrom R, Ma Z, Davis C, Pope BD, Shen Y, Pervouchine DD, Djebali S, Thurman RE, Kaul R, Rynes E, Kirilusha A, Marinov GK, Williams BA, Trout D, Amrhein H, Fisher-Aylor K, Antoshechkin I, DeSalvo G, See LH, Fastuca M, Drenkow J, Zaleski C, Dobin A, Prieto P, Lagarde J, Bussotti G, Tanzer A, Denas O, Li K, Bender MA, Zhang M, Byron R, Groudine MT, McCleary D, Pham L, Ye Z, Kuan S, Edsall L, Wu YC, Rasmussen MD, Bansal MS, Kellis M, Keller CA, Morrissey CS, Mishra T, Jain D, Dogan N, Harris RS, Cayting P, Kawli T, Boyle AP, Euskirchen G, Kundaje A, Lin S, Lin Y, Jansen C, Malladi VS, Cline MS, Erickson DT, Kirkup VM, Learned K, Sloan CA, Rosenbloom KR, Lacerda de Sousa B, Beal K, Pignatelli M, Flicek P, Lian J, Kahveci T, Lee D, Kent WJ, Ramalho Santos M, Herrero J, Notredame C, Johnson A, Vong S, Lee K, Bates D, Neri F, Diegel M, Canfield T, Sabo PJ, Wilken MS, Reh TA, Giste E, Shafer A, Kutyavin T, Haugen E, Dunn D, Reynolds AP, Neph S, Humbert R, Hansen RS, De Bruijn M, Selleri L, Rudensky A, Josefowicz S, Samstein R, Eichler EE, Orkin SH, Levasseur D, Papayannopoulou T, Chang KH, Skoultchi A, Gosh S, Disteche C, Treuting P, Wang Y, Weiss MJ, Blobel GA, Cao X, Zhong S, Wang T, Good PJ, Lowdon RF, Adams LB, Zhou XQ, Pazin MJ, Feingold EA, Wold B, Taylor J, Mortazavi A, Weissman SM, Stamatoyannopoulos JA, Snyder MP, Guigo R, Gingeras TR, Gilbert DM, Hardison RC, Beer MA, Ren B