Chongyuan Luo

Assistant Professor, Human Genetics, University of California Los Angeles

We are interested in studying how gene regulatory mechanisms contribute to human diseases including neurodevelopmental disorders. Many genome-wide association studies (GWAS) of diseases have identified the enrichment of non-coding risk variants in regulatory elements such as enhancers, highlighting the contribution of regulatory mechanisms to complex traits. In addition, epigenetic variants, such as cytosine methylation (5mC), have been reported to associate with diseases and can be driven by genetic, environmental or stochastic factors. We are developing and applying new genomic and genetic technologies to address long-standing questions in human diseases including the causal cell type(s) of diseases and the functions of non-coding genetic variants. Two major areas of research in my group are described below. Developing new epigenomic technologies. Genomic profiling of epigenomic signatures (e.g. DNA methylation, histone modifications) enables the study of gene regulatory events at a global scale. In previous work, we have developed single-cell epigenomic and multi-omic technologies, and use these methods to study the gene regulatory diversity in the brain. We developed a high-throughput single-cell methylome profiling method snmC-seq and its major update snmC-seq2 that have enabled cell-type classification and the identification of cell-type-specific regulatory elements across cortical neuron subtypes in mouse and human (Luo et al., 2017. Science; Luo et al., 2018. Nature Communications). More recently we have developed two single-cell multi-omic methods that allow the multi-modal integration of transcriptome, DNA methylome, chromatin accessibility and chromatin conformation (Luo*, Liu*, Xie* et al., 2022. Cell Genomics; Lee*, Luo*, Zhou* et al., 2019. Nature Methods), providing a near-comprehensive epigenomic characterization of individual brain cells. Genetic basis of neurodevelopmental disorders. Psychiatric neurodevelopmental disorders such as schizophrenia and autism spectrum disorders (ASD) are highly heritable. Regulatory mechanisms play an important role in both diseases and schizophrenia risk variants are enriched in bulk brain tissue enhancers and immune cell types. Importantly, ASD can be contributed by epigenetic regulation by 5mC. Rett’s syndrome is a type of ASD and is caused by mutations in MECP2 (methyl-CpG binding protein 2) that recognize 5mC. Neurodevelopmental disorders are likely contributed by multiple cell types in developing and adult brains. We will use a combination of single-cell multi-epigenomics and population genetics approaches to address the contribution of aberrant gene regulations in neurodevelopmental disorders.

Education and Training

Salk Institute for Biological StudiesPostdoc08/2019Epigenomics
Rutgers, The State University of New JerseyPh.D.05/2012Plant Biology

Publications

  1. Chien JF, Liu H, Wang BA, Luo C, Bartlett A, Castanon R, Johnson ND, Nery JR, Osteen J, Li J, Altshul J, Kenworthy M, Valadon C, Liem M, Claffey N, O'Connor C, Seeker LA, Ecker JR, Behrens MM, Mukamel EA. Cell-type-specific effects of age and sex on human cortical neurons.. Neuron, 2024.
  2. Chen PB, Chen R, LaPierre N, Chen Z, Mefford J, Marcus E, Heffel MG, Soto DC, Ernst J, Luo C, Flint J. Complementation testing identifies genes mediating effects at quantitative trait loci underlying fear-related behavior.. Cell genomics, 2024.
  3. Zhou J, Luo C, Liu H, Heffel MG, Straub RE, Kleinman JE, Hyde TM, Ecker JR, Weinberger DR, Han S. scMeFormer: a transformer-based deep learning model for imputing DNA methylation states in single cells enhances the detection of epigenetic alterations in schizophrenia.. bioRxiv : the preprint server for biology, 2024.
  4. Liu H, Zeng Q, Zhou J, Bartlett A, Wang BA, Berube P, Tian W, Kenworthy M, Altshul J, Nery JR, Chen H, Castanon RG, Zu S, Li YE, Lucero J, Osteen JK, Pinto-Duarte A, Lee J, Rink J, Cho S, Emerson N, Nunn M, O'Connor C, Wu Z, Stoica I, Yao Z, Smith KA, Tasic B, Luo C, Dixon JR, Zeng H, Ren B, Behrens MM, Ecker JR. Single-cell DNA methylome and 3D multi-omic atlas of the adult mouse brain.. Nature, 2023.
  5. Flint J, Heffel MG, Chen Z, Mefford J, Marcus E, Chen PB, Ernst J, Luo C. Single-cell methylation analysis of brain tissue prioritizes mutations that alter transcription.. Cell genomics, 2023.
  6. Xie F, Armand EJ, Yao Z, Liu H, Bartlett A, Behrens MM, Li YE, Lucero JD, Luo C, Nery JR, Pinto-Duarte A, Poirion OB, Preissl S, Rivkin AC, Tasic B, Zeng H, Ren B, Ecker JR, Mukamel EA. Robust enhancer-gene regulation identified by single-cell transcriptomes and epigenomes.. Cell genomics, 2023.
  7. Liu H, Zeng Q, Zhou J, Bartlett A, Wang BA, Berube P, Tian W, Kenworthy M, Altshul J, Nery JR, Chen H, Castanon RG, Zu S, Li YE, Lucero J, Osteen JK, Pinto-Duarte A, Lee J, Rink J, Cho S, Emerson N, Nunn M, O'Connor C, Yao Z, Smith KA, Tasic B, Zeng H, Luo C, Dixon JR, Ren B, Behrens MM, Ecker JR. Single-cell DNA Methylome and 3D Multi-omic Atlas of the Adult Mouse Brain.. bioRxiv : the preprint server for biology, 2023.
  8. Gandal MJ, Haney JR, Wamsley B, Yap CX, Parhami S, Emani PS, Chang N, Chen GT, Hoftman GD, de Alba D, Ramaswami G, Hartl CL, Bhattacharya A, Luo C, Jin T, Wang D, Kawaguchi R, Quintero D, Ou J, Wu YE, Parikshak NN, Swarup V, Belgard TG, Gerstein M, Pasaniuc B, Geschwind DH. Broad transcriptomic dysregulation occurs across the cerebral cortex in ASD.. Nature, 2022.
  9. Li J, Pinto-Duarte A, Zander M, Cuoco MS, Lai CY, Osteen J, Fang L, Luo C, Lucero JD, Gomez-Castanon R, Nery JR, Silva-Garcia I, Pang Y, Sejnowski TJ, Powell SB, Ecker JR, Mukamel EA, Behrens MM. Dnmt3a knockout in excitatory neurons impairs postnatal synapse maturation and increases the repressive histone modification H3K27me3.. eLife, 2022.
  10. Guo L, Boocock J, Hilt EE, Chandrasekaran S, Zhang Y, Munugala C, Sathe L, Alexander N, Arboleda VA, Flint J, Eskin E, Luo C, Yang S, Garner OB, Yin Y, Bloom JS, Kruglyak L. Genomic epidemiology of the Los Angeles COVID-19 outbreak and the early history of the B.1.43 strain in the USA.. BMC genomics, 2022.
  11. Bakken TE, Jorstad NL, Hu Q, Lake BB, Tian W, Kalmbach BE, Crow M, Hodge RD, Krienen FM, Sorensen SA, Eggermont J, Yao Z, Aevermann BD, Aldridge AI, Bartlett A, Bertagnolli D, Casper T, Castanon RG, Crichton K, Daigle TL, Dalley R, Dee N, Dembrow N, Diep D, Ding SL, Dong W, Fang R, Fischer S, Goldman M, Goldy J, Graybuck LT, Herb BR, Hou X, Kancherla J, Kroll M, Lathia K, van Lew B, Li YE, Liu CS, Liu H, Lucero JD, Mahurkar A, McMillen D, Miller JA, Moussa M, Nery JR, Nicovich PR, Niu SY, Orvis J, Osteen JK, Owen S, Palmer CR, Pham T, Plongthongkum N, Poirion O, Reed NM, Rimorin C, Rivkin A, Romanow WJ, Sedeño-Cortés AE, Siletti K, Somasundaram S, Sulc J, Tieu M, Torkelson A, Tung H, Wang X, Xie F, Yanny AM, Zhang R, Ament SA, Behrens MM, Bravo HC, Chun J, Dobin A, Gillis J, Hertzano R, Hof PR, Höllt T, Horwitz GD, Keene CD, Kharchenko PV, Ko AL, Lelieveldt BP, Luo C, Mukamel EA, Pinto-Duarte A, Preiss S, Regev A, Ren B, Scheuermann RH, Smith K, Spain WJ, White OR, Koch C, Hawrylycz M, Tasic B, Macosko EZ, McCarroll SA, Ting JT, Zeng H, Zhang K, Feng G, Ecker JR, Linnarsson S, Lein ES. Author Correction: Comparative cellular analysis of motor cortex in human, marmoset and mouse.. Nature, 2022.
  12. Luo C, Liu H, Xie F, Armand EJ, Siletti K, Bakken TE, Fang R, Doyle WI, Stuart T, Hodge RD, Hu L, Wang BA, Zhang Z, Preissl S, Lee DS, Zhou J, Niu SY, Castanon R, Bartlett A, Rivkin A, Wang X, Lucero J, Nery JR, Davis DA, Mash DC, Satija R, Dixon JR, Linnarsson S, Lein E, Behrens MM, Ren B, Mukamel EA, Ecker JR. Single nucleus multi-omics identifies human cortical cell regulatory genome diversity.. Cell genomics, 2022.
  13. Yao Z, Liu H, Xie F, Fischer S, Adkins RS, Aldridge AI, Ament SA, Bartlett A, Behrens MM, Van den Berge K, Bertagnolli D, de Bézieux HR, Biancalani T, Booeshaghi AS, Bravo HC, Casper T, Colantuoni C, Crabtree J, Creasy H, Crichton K, Crow M, Dee N, Dougherty EL, Doyle WI, Dudoit S, Fang R, Felix V, Fong O, Giglio M, Goldy J, Hawrylycz M, Herb BR, Hertzano R, Hou X, Hu Q, Kancherla J, Kroll M, Lathia K, Li YE, Lucero JD, Luo C, Mahurkar A, McMillen D, Nadaf NM, Nery JR, Nguyen TN, Niu SY, Ntranos V, Orvis J, Osteen JK, Pham T, Pinto-Duarte A, Poirion O, Preissl S, Purdom E, Rimorin C, Risso D, Rivkin AC, Smith K, Street K, Sulc J, Svensson V, Tieu M, Torkelson A, Tung H, Vaishnav ED, Vanderburg CR, van Velthoven C, Wang X, White OR, Huang ZJ, Kharchenko PV, Pachter L, Ngai J, Regev A, Tasic B, Welch JD, Gillis J, Macosko EZ, Ren B, Ecker JR, Zeng H, Mukamel EA. A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex.. Nature, 2021.
  14. Bakken TE, Jorstad NL, Hu Q, Lake BB, Tian W, Kalmbach BE, Crow M, Hodge RD, Krienen FM, Sorensen SA, Eggermont J, Yao Z, Aevermann BD, Aldridge AI, Bartlett A, Bertagnolli D, Casper T, Castanon RG, Crichton K, Daigle TL, Dalley R, Dee N, Dembrow N, Diep D, Ding SL, Dong W, Fang R, Fischer S, Goldman M, Goldy J, Graybuck LT, Herb BR, Hou X, Kancherla J, Kroll M, Lathia K, van Lew B, Li YE, Liu CS, Liu H, Lucero JD, Mahurkar A, McMillen D, Miller JA, Moussa M, Nery JR, Nicovich PR, Niu SY, Orvis J, Osteen JK, Owen S, Palmer CR, Pham T, Plongthongkum N, Poirion O, Reed NM, Rimorin C, Rivkin A, Romanow WJ, Sedeño-Cortés AE, Siletti K, Somasundaram S, Sulc J, Tieu M, Torkelson A, Tung H, Wang X, Xie F, Yanny AM, Zhang R, Ament SA, Behrens MM, Bravo HC, Chun J, Dobin A, Gillis J, Hertzano R, Hof PR, Höllt T, Horwitz GD, Keene CD, Kharchenko PV, Ko AL, Lelieveldt BP, Luo C, Mukamel EA, Pinto-Duarte A, Preissl S, Regev A, Ren B, Scheuermann RH, Smith K, Spain WJ, White OR, Koch C, Hawrylycz M, Tasic B, Macosko EZ, McCarroll SA, Ting JT, Zeng H, Zhang K, Feng G, Ecker JR, Linnarsson S, Lein ES. Comparative cellular analysis of motor cortex in human, marmoset and mouse.. Nature, 2021.
  15. Liu H, Zhou J, Tian W, Luo C, Bartlett A, Aldridge A, Lucero J, Osteen JK, Nery JR, Chen H, Rivkin A, Castanon RG, Clock B, Li YE, Hou X, Poirion OB, Preissl S, Pinto-Duarte A, O'Connor C, Boggeman L, Fitzpatrick C, Nunn M, Mukamel EA, Zhang Z, Callaway EM, Ren B, Dixon JR, Behrens MM, Ecker JR. DNA methylation atlas of the mouse brain at single-cell resolution.. Nature, 2021.
  16. Bloom JS, Sathe L, Munugala C, Jones EM, Gasperini M, Lubock NB, Yarza F, Thompson EM, Kovary KM, Park J, Marquette D, Kay S, Lucas M, Love T, Sina Booeshaghi A, Brandenberg OF, Guo L, Boocock J, Hochman M, Simpkins SW, Lin I, LaPierre N, Hong D, Zhang Y, Oland G, Choe BJ, Chandrasekaran S, Hilt EE, Butte MJ, Damoiseaux R, Kravit C, Cooper AR, Yin Y, Pachter L, Garner OB, Flint J, Eskin E, Luo C, Kosuri S, Kruglyak L, Arboleda VA. Massively scaled-up testing for SARS-CoV-2 RNA via next-generation sequencing of pooled and barcoded nasal and saliva samples.. Nature biomedical engineering, 2021.
  17. Gao C, Liu J, Kriebel AR, Preissl S, Luo C, Castanon R, Sandoval J, Rivkin A, Nery JR, Behrens MM, Ecker JR, Ren B, Welch JD. Iterative single-cell multi-omic integration using online learning.. Nature biotechnology, 2021.
  18. Evrony GD, Hinch AG, Luo C. Applications of Single-Cell DNA Sequencing.. Annual review of genomics and human genetics, 2021.
  19. Bloom JS, Sathe L, Munugala C, Jones EM, Gasperini M, Lubock NB, Yarza F, Thompson EM, Kovary KM, Park J, Marquette D, Kay S, Lucas M, Love T, Booeshaghi AS, Brandenberg OF, Guo L, Boocock J, Hochman M, Simpkins SW, Lin I, LaPierre N, Hong D, Zhang Y, Oland G, Choe BJ, Chandrasekaran S, Hilt EE, Butte MJ, Damoiseaux R, Kravit C, Cooper AR, Yin Y, Pachter L, Garner OB, Flint J, Eskin E, Luo C, Kosuri S, Kruglyak L, Arboleda VA. Swab-Seq: A high-throughput platform for massively scaled up SARS-CoV-2 testing.. medRxiv : the preprint server for health sciences, 2021.
  20. Armand EJ, Li J, Xie F, Luo C, Mukamel EA. Single-Cell Sequencing of Brain Cell Transcriptomes and Epigenomes.. Neuron, 2021.
  21. He Y, Hariharan M, Gorkin DU, Dickel DE, Luo C, Castanon RG, Nery JR, Lee AY, Zhao Y, Huang H, Williams BA, Trout D, Amrhein H, Fang R, Chen H, Li B, Visel A, Pennacchio LA, Ren B, Ecker JR. Spatiotemporal DNA methylome dynamics of the developing mouse fetus.. Nature, 2020.
  22. Lavery LA, Ure K, Wan YW, Luo C, Trostle AJ, Wang W, Jin H, Lopez J, Lucero J, Durham MA, Castanon R, Nery JR, Liu Z, Goodell M, Ecker JR, Behrens MM, Zoghbi HY. Losing Dnmt3a dependent methylation in inhibitory neurons impairs neural function by a mechanism impacting Rett syndrome.. eLife, 2020.
  23. Lee DS, Luo C, Zhou J, Chandran S, Rivkin A, Bartlett A, Nery JR, Fitzpatrick C, O'Connor C, Dixon JR, Ecker JR. Simultaneous profiling of 3D genome structure and DNA methylation in single human cells.. Nature methods, 2019.
  24. Luo C, Lee QY, Wapinski O, Castanon R, Nery JR, Mall M, Kareta MS, Cullen SM, Goodell MA, Chang HY, Wernig M, Ecker JR. Global DNA methylation remodeling during direct reprogramming of fibroblasts to neurons.. eLife, 2019.
  25. Luo C, Hajkova P, Ecker JR. Dynamic DNA methylation: In the right place at the right time.. Science (New York, N.Y.), 2018.
  26. Luo C, Rivkin A, Zhou J, Sandoval JP, Kurihara L, Lucero J, Castanon R, Nery JR, Pinto-Duarte A, Bui B, Fitzpatrick C, O'Connor C, Ruga S, Van Eden ME, Davis DA, Mash DC, Behrens MM, Ecker JR. Robust single-cell DNA methylome profiling with snmC-seq2.. Nature communications, 2018.
  27. Sabbagh MF, Heng JS, Luo C, Castanon RG, Nery JR, Rattner A, Goff LA, Ecker JR, Nathans J. Transcriptional and epigenomic landscapes of CNS and non-CNS vascular endothelial cells.. eLife, 2018.
  28. Luo C, Keown CL, Kurihara L, Zhou J, He Y, Li J, Castanon R, Lucero J, Nery JR, Sandoval JP, Bui B, Sejnowski TJ, Harkins TT, Mukamel EA, Behrens MM, Ecker JR. Single-cell methylomes identify neuronal subtypes and regulatory elements in mammalian cortex.. Science (New York, N.Y.), 2017.
  29. Luo C, Lancaster MA, Castanon R, Nery JR, Knoblich JA, Ecker JR. Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain.. Cell reports, 2016.
  30. Chin CS, Peluso P, Sedlazeck FJ, Nattestad M, Concepcion GT, Clum A, Dunn C, O'Malley R, Figueroa-Balderas R, Morales-Cruz A, Cramer GR, Delledonne M, Luo C, Ecker JR, Cantu D, Rank DR, Schatz MC. Phased diploid genome assembly with single-molecule real-time sequencing.. Nature methods, 2016.
  31. Mo A, Luo C, Davis FP, Mukamel EA, Henry GL, Nery JR, Urich MA, Picard S, Lister R, Eddy SR, Beer MA, Ecker JR, Nathans J. Epigenomic landscapes of retinal rods and cones.. eLife, 2016.
  32. Mo A, Mukamel EA, Davis FP, Luo C, Henry GL, Picard S, Urich MA, Nery JR, Sejnowski TJ, Lister R, Eddy SR, Ecker JR, Nathans J. Epigenomic Signatures of Neuronal Diversity in the Mammalian Brain.. Neuron, 2015.
  33. Luo C, Ecker JR. Epigenetics. Exceptional epigenetics in the brain.. Science (New York, N.Y.), 2015.
  34. Wu J, Okamura D, Li M, Suzuki K, Luo C, Ma L, He Y, Li Z, Benner C, Tamura I, Krause MN, Nery JR, Du T, Zhang Z, Hishida T, Takahashi Y, Aizawa E, Kim NY, Lajara J, Guillen P, Campistol JM, Esteban CR, Ross PJ, Saghatelian A, Ren B, Ecker JR, Izpisua Belmonte JC. An alternative pluripotent state confers interspecies chimaeric competency.. Nature, 2015.
  35. Luo C, Dong J, Zhang Y, Lam E. Decoding the role of chromatin architecture in development: coming closer to the end of the tunnel.. Frontiers in plant science, 2014.
  36. Widiez T, Symeonidi A, Luo C, Lam E, Lawton M, Rensing SA. The chromatin landscape of the moss Physcomitrella patens and its dynamics during development and drought stress.. The Plant journal : for cell and molecular biology, 2014.
  37. Luo C, Lam E. Quantitatively profiling genome-wide patterns of histone modifications in Arabidopsis thaliana using ChIP-seq.. Methods in molecular biology (Clifton, N.J.), 2014.
  38. Luo C, Sidote DJ, Zhang Y, Kerstetter RA, Michael TP, Lam E. Integrative analysis of chromatin states in Arabidopsis identified potential regulatory mechanisms for natural antisense transcript production.. The Plant journal : for cell and molecular biology, 2012.
  39. Vaquero-Sedas MI, Luo C, Vega-Palas MA. Analysis of the epigenetic status of telomeres by using ChIP-seq data.. Nucleic acids research, 2012.
  40. Amini A, Luo C, Lam E. Chromatin beacons: global sampling of chromatin physical properties using chromatin charting lines.. Methods in molecular biology (Clifton, N.J.), 2011.
  41. Luo C, Lam E. ANCORP: a high-resolution approach that generates distinct chromatin state models from multiple genome-wide datasets.. The Plant journal : for cell and molecular biology, 2010.
  42. Luo C, Durgin BG, Watanabe N, Lam E. Defining the functional network of epigenetic regulators in Arabidopsis thaliana.. Molecular plant, 2009.
  43. Lam E, Luo C, Watanabe N. Charting functional and physical properties of chromatin in living cells.. Current opinion in genetics & development, 2009.
  44. Luo C, Lam E. Chromatin charting: global mapping of epigenetic effects.. Methods in molecular biology (Clifton, N.J.), 2009.
  45. Rotter D, Bharti AK, Li HM, Luo C, Bonos SA, Bughrara S, Jung G, Messing J, Meyer WA, Rudd S, Warnke SE, Belanger FC. Analysis of EST sequences suggests recent origin of allotetraploid colonial and creeping bentgrasses.. Molecular genetics and genomics : MGG, 2007.