Yang Lab

Research

We are interested in the neurobiological foundations underlying the causes, mechanisms, and trajectories of psychiatric and neurological disorders. Our work is deeply rooted in development. We take advantage of human pluripotent stem cells to reconstitute and understand human brain development. By developing new high-throughput in vitro model systems and employing single-cell omics approaches, we seek to understand how neural tissue is established during fetal development, how neurons form interconnected networks, and how they vary among individuals and in psychiatric and neurological disorders. We are committed to uncovering the regulatory networks that control stem cell differentiation and developing novel methods to increase the precision and safety of stem cell-based therapies. In addition to the in vitro model systems, we develop and use new experimentally tractable animal models of human disease to interrogate disease mechanisms and discover new therapeutic opportunities.

Yang Laboratory
Nan Yang, Ph.D.
Associate Professor, Neuroscience
Location
Lab: Ichan 13-52
Office: Icahn 13-20D
Phone
Office: 212-659-8288
Lab: 212-559-1379
Email: nan.yang1@mssm.edu

Projects

Brain development and Reprogram

The formation of the central nervous system is a remarkable process that starts with the generation of and interaction between diverse cell types. Using single-cell profiling that captures cell identity and cell states within a complex tissue, our work seeks to unveil the series of rules underlying the extraordinary cellular diversity and human brain organization. By applying our knowledge of development, we recreate 2D and 3D in vitro systems to recapitulate key events during human brain development. These systems promise to uncover the principles of cell diversification and create a platform for stem cell-based disease investigation.

 

Neurodevelopmental Disorders

Our team aims to translate genetic discoveries from human studies into actionable biological hypotheses and provide new insights into the causal chain of events that result in neurological and psychiatric disease conditions. Together with the Seaver Autism Center at Mount Sinai, we apply human stem cell-based and mouse model systems and use multidisciplinary approaches, including CRISPR gene editing, electrophysiology, single-cell sequencing, and high-resolution imaging, to learn how the disease-associated genetic variation impairs neuronal properties and circuit activities. We also employ brain organoids combined with live-imaging and single-cell profiling to study the early molecular and cellular events, such as cell proliferation, migration, and differentiation impaired by disease-risk variants identified in recent large-scale genomic studies.

Neuroepigenetics and diseases

Disorders of the brain affect nearly one-fifth of the world’s population. Although genome-wide association studies (GWAS) have identified many genetic variants strongly linked to neurological and psychiatric disorders, functional interpretation is challenging. Most heritable common disease risk distributes to non-coding regions and appears to be particularly enriched in enhancers (classically defined as cis-acting DNA sequences that can increase the transcription of genes) that are specific to disease-relevant cell types. However, only a handful of the enhancers nominated via biochemical annotations have been validated and confidently linked to their target genes. We use innovative multidisciplinary approaches built upon stem cell technology to unravel the functions of non-coding sequences in disease-relevant neuronal types. This work promises an exploration of the biological functions of non-coding regions containing disease risk variants and helps bridge the gap between human genetics and experimental biology.

Publications

2022

Mapping cis-regulatory elements in human neurons links psychiatric disease heritability and activity-regulated transcriptional programs 

Sanchez-Priego C, Hu R, Boshans LL, Lalli M, Janas JA, Williams SE, Dong Z, Yang N, Cell Reports. 2022

Generation of Functional Human Oligodendrocytes from Dermal Fibroblasts by Direct Lineage Conversion

Tanabe K, Nobuta H, Yang N, Ang CE, Huie Jr P, Jordan S, Oldham MC, Rowitch DH, Wernig M, Development. 2022 (in press) 
2021

Direct Differentiation of Functional Neurons from Human Pluripotent Stem Cells (hPSCs).

Hu R, Zhu X, Yang N.Methods Mol Biol. 2021;2352:117-126.

Efficient generation of dopaminergic induced neuronal cells with midbrain characteristics.

Ng YH, Chanda S, Janas JA, Yang N, Kokubu Y, Südhof TC, Wernig M. Stem Cell Reports. 2021 Jul 13;16(7):1763-1776.
2019

Oligodendrocyte Death in Pelizaeus-Merzbacher Disease Is Rescued by Iron Chelation.

Nobuta H, Yang N, Ng YH, Marro SG, Sabeur K, Chavali M, Stockley JH, Killilea DW, Walter PB, Zhao C, Huie P Jr, Goldman SA, Kriegstein AR, Franklin RJM, Rowitch DH, Wernig M. Cell Stem Cell. 2019 Oct 3;25(4):531-541.e6.

In Vitro Modeling of the Bipolar Disorder and Schizophrenia Using Patient-Derived Induced Pluripotent Stem Cells with Copy Number Variations of PCDH15 and RELN.

Ishii T, Ishikawa M, Fujimori K, Maeda T, Kushima I, Arioka Y, Mori D, Nakatake Y, Yamagata B, Nio S, Kato TA, Yang N, Wernig M, Kanba S, Mimura M, Ozaki N, Okano H.eNeuro. 2019 Oct 17;6(5):ENEURO.0403-18.2019.

Neuroligin-4 Regulates Excitatory Synaptic Transmission in Human Neurons.

Marro SG, Chanda S, Yang N, Janas JA, Valperga G, Trotter J, Zhou B, Merrill S, Yousif I, Shelby H, Vogel H, Kalani MYS, Südhof TC, Wernig M.Neuron. 2019 Aug 21;103(4):617-626.e6. 
2018

The fragile X mutation impairs homeostatic plasticity in human neurons by blocking synaptic retinoic acid signaling.

Zhang Z, Marro SG, Zhang Y, Arendt KL, Patzke C, Zhou B, Fair T, Yang N, Südhof TC, Wernig M, Chen L.Sci Transl Med. 2018 Aug 1;10(452):eaar4338
2017

A Peek into Parkinson’s Disease Progression through Human Dopamine Neurons in a Dish.

Yang N, Yue Z.Trends Neurosci. 2018 Feb;41(2):74-76. 

μNeurocircuitry: Establishing in vitro models of neurocircuits with human neurons.

Fantuzzo JA, De Filippis L, McGowan H, Yang N, Ng YH, Halikere A, Liu JJ, Hart RP, Wernig M, Zahn JD, Pang ZP.Technology (Singap World Sci). 2017 Jun;5(2):87-97.

Generation of pure GABAergic neurons by transcription factor programming.

Yang N, Chanda S, Marro S, Ng YH, Janas JA, Haag D, Ang CE, Tang Y, Flores Q, Mall M, Wapinski O, Li M, Ahlenius H, Rubenstein JL, Chang HY, Buylla AA, Südhof TC, Wernig M.Nat Methods. 2017 Jun;14(6):621-628. 
Earlier than 2015

Transdifferentiation of mouse fibroblasts and hepatocytes to functional neurons.

Marro S, Yang N.Methods Mol Biol. 2014;1150:237-46.

Harnessing the stem cell potential: a case for neural stem cell therapy.

Yang N, Wernig M.Nat Med. 2013 Dec;19(12):1580-1.

Rapid single-step induction of functional neurons from human pluripotent stem cells.

Zhang Y, Pak C, Han Y, Ahlenius H, Zhang Z, Chanda S, Marro S, Patzke C, Acuna C, Covy J, Xu W, Yang N, Danko T, Chen L, Wernig M, Südhof TC.Neuron. 2013 Jun 5;78(5):785-98.

Generation of oligodendroglial cells by direct lineage conversion.

Yang N, Zuchero JB, Ahlenius H, Marro S, Ng YH, Vierbuchen T, Hawkins JS, Geissler R, Barres BA, Wernig M.Nat Biotechnol. 2013 May;31(5):434-9

Induced neuronal cells: how to make and define a neuron.

Yang N, Ng YH, Pang ZP, Südhof TC, Wernig M.Cell Stem Cell. 2011 Dec 2;9(6):517-25. 

Direct lineage conversion of terminally differentiated hepatocytes to functional neurons.

Marro S, Pang ZP, Yang N, Tsai MC, Qu K, Chang HY, Südhof TC, Wernig M.Cell Stem Cell. 2011 Oct 4;9(4):374-82. 

Induction of human neuronal cells by defined transcription factors.

Pang ZP*, Yang N*, Vierbuchen T*, Ostermeier A, Fuentes DR, Yang TQ, Citri A, Sebastiano V, Marro S, Südhof TC, Wernig M.Nature. 2011 May 26;476(7359):220-3. (* equal contribution)

Genomic selection identifies vertebrate transcription factor Fezf2 binding sites and target genes.

Chen L, Zheng J, Yang N, Li H, Guo SJ Biol Chem. 2011 May 27;286(21):18641-9.

A systematic approach to identify functional motifs within vertebrate developmental enhancers.

Li Q, Ritter D, Yang N, Dong Z, Li H, Chuang JH, Guo SDev Biol. 2010 Jan 15;337(2):484-95.

A subunit of the mediator complex regulates vertebrate neuronal development.

Wang X, Yang N, Uno E, Roeder RG, Guo S. Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17284-9. 

Meet the Team

Aleta Murphy

Aleta Murphy

Graduate student

Aleta Murphy is a Ph.D. student in the Neuroscience MTA. She is interested in using 2D and 3D human induced pluripotent stem cell technologies to investigate the impact of autism spectrum disorders (ASD) -associated genetic mutations on neural development and function. Previously, Aleta earned her Master’s of Biomedical Science at Mount Sinai in the lab of Dr. Kristen Brennand. Outside of the lab, Aleta enjoys reading mystery novels, picnicking in Central Park, and consuming lots of bubble tea. 

Henry Kim

Henry Kim

Undergraduate student

Henry is a Research Associate working in both Dr. Nan Yang and Dr. Zhenyu Yue’s labs. His current project works to elucidate novel adaptors in the selective degradation of the endoplasmic reticulum. When he is not working, he likes to spend time with his dogs and listen to music and podcasts.

Linda Lee

Linda Lee

Postdoc

Linda is a postdoctoral fellow in the department of neuroscience. Her project involves using iPS cell-derived 3D cerebral organoids to investigate the role of NF1 on cellular and molecular mechanisms of early brain development. In her free time, she enjoys dancing, biking, traveling, and making ice cream.

Ruiqi (Rachel) Hu

Ruiqi (Rachel) Hu

Postdoctoral Fellow

Ruiqi is a Postdoctoral Fellow. Before taking this position, she performed her graduate thesis project as a visiting student from Huazhong Agriculture University. Ruiqi is interested in understanding molecular mechanisms underlying human neurogenesis and developing novel human models to investigate neurological and psychiatric diseases. Her current project focuses on developing high-throughput approaches to study autism-associated variants revealed by human genetic studies. Outside of the lab, Ruiqi enjoys reading novels, doing sports, listening to music, and doing crafts.

Sarah Williams

Sarah Williams

Graduate student

Sarah is a Ph.D. student in the department of neuroscience, co-mentored by Dr. Kristen Brennand of Yale University. She is interested in using human stem cell models to study genetic risk for psychiatric disorders, with an emphasis on cell-type-specific effects, non-coding variants, and multiplexing strategies. Outside of lab, Sarah enjoys traveling, photography, and exploring all of NYC’s museums, live shows, and antique shops.

Xiaoting Zhou

Xiaoting Zhou

Graduate student

Alida Pahlevan

Alida Pahlevan

Undergraduate student

Alida Pahlevan used to be a research intern during the summer of 2019 in your lab when she was in high school. She is now rejoining the team for the summer as an honors student at Northeastern University, majoring in Neuroscience on a pre-med track. 

Jacqueline (Jackie) Cho

Jacqueline (Jackie) Cho

Undergraduate student

Jacqueline (Jackie) Cho is an undergraduate student at Brown University currently completing her B.S. degree in neuroscience. Jackie received the Seaver Undergraduate Research Scholars – Summer 2022 and will work on an autism risk gene DDX3X function.

Lab Alumni

Gizem Inak Girrbach (Nuvisan ICB in Berlin, Associate Scientist): postdoc (2020-2021)

Carlos Sanchez-Priego (Genentech Inc.): graduate student (2017 – 2021)

Stephanie Rogers (University of Cambridge): research assistant (2018 – 2019)

Gallery and News

June 2022

  • Summer is here, and so are our summer students! Welcome to the lab, Alida Pahlevan and Jacqueline Cho

May 2022

  • IT IS OFFICIAL, Sarah is now a Ph.D. candidate in Neuroscience.
  • The manuscript Mapping cis-regulatory elements in human neurons links psychiatric disease heritability and activity-regulated transcriptional programs was accepted by Cell Reports. Congratulations to every contributing author, especially Carlos, Ruiqi, and Linda!

February 2022

  • Aleta joined the lab for her Ph.D. – Welcome to the lab!
  • Sarah received the Seaver Fellowship – Congratulations!

November 2021

  • Congratulations, Dr. Carlos Sanchez-Priego on your successful thesis defense.
  • Linda received the NYSTEM Fellowship – Congratulations!

August 2021

  • Sarah joined the lab for her Ph.D. – Welcome to the lab!

Contact us

Whether you’re looking to collaborate or want to become an ambitious scientist and become part of our team,  the Yang lab is eager to connect. Please email us (nan.yang1@mssm.edu).