Xinshu Grace Xiao

Laboratory Address:
Terasaki Life Sciences Building, 2045

Office Address:
Terasaki Life Sciences Building, 2000E
Los Angeles,

Professor, Integrative Biology and Physiology
Member, Bioinformatics GPB Home Area, Gene Regulation GPB Home Area, JCCC Gene Regulation Program Area, Molecular, Cellular & Integrative Physiology GPB Home Area
Research Interests
With similar number of genes as in simpler organisms, mammals demonstrate an amazing degree of phenotypic diversity. Mammalian gene expression is under tight regulation temporally and spatially, which contributes to the formation of different cell types, tissues, and organs. Gene regulation involves a complex network of players, including multiple DNA, RNA sequence elements and RNA and protein factors. These regulators interact with each other and carry out combinatorial regulatory functions. Our lab uses both computational and experimental approaches to study the biology of gene regulation from a systems point of view. Our current focus pertains to the regulation of gene expression at the RNA level via the process of pre-mRNA splicing and other post-transcriptional (or co-transcriptional) mechanisms. Splicing is a critical step enabling diversity in gene expression programs. At least half of all human genes undergo alternative splicing which allows multiple gene products with potentially different functions to be produced from a single gene locus. We are currently investigating splicing regulatory mechanisms using comparative genomics, high-throughput technologies, such as deep sequencing and microarrays, and systems level computational analysis, such as system identification and modeling approaches. A long-term goal of our research is to better understand the involvement of splicing in gene expression programs of different disease models.

A selected list of publications:

Hsiao Yun-Hua Esther, Bahn Jae Hoon, Lin Xianzhi, Chan Tak-Ming, Wang Rena, Xiao Xinshu   Alternative splicing modulated by genetic variants demonstrates accelerated evolution regulated by highly conserved proteins Genome research, 2016; 26(4): 440-50.
Cass Ashley A, Bahn Jae Hoon, Lee Jae-Hyung, Greer Christopher, Lin Xianzhi, Kim Yong, Hsiao Yun-Hua Esther, Xiao Xinshu   Global analyses of endonucleolytic cleavage in mammals reveal expanded repertoires of cleavage-inducing small RNAs and their targets Nucleic acids research, 2016; 44(7): 3253-63.
Fuxjager Matthew J, Lee Jae-Hyung, Chan Tak-Ming, Bahn Jae Hoon, Chew Jenifer G, Xiao Xinshu, Schlinger Barney A   Research Resource: Hormones, Genes, and Athleticism: Effect of Androgens on the Avian Muscular Transcriptome Molecular endocrinology (Baltimore, Md.), 2016; 30(2): 254-71.
Gao Chen, Ren Shuxun, Lee Jae-Hyung, Qiu Jinsong, Chapski Douglas J, Rau Christoph D, Zhou Yu, Abdellatif Maha, Nakano Astushi, Vondriska Thomas M, Xiao Xinshu, Fu Xiang-Dong, Chen Jau-Nian, Wang Yibin   RBFox1-mediated RNA splicing regulates cardiac hypertrophy and heart failure The Journal of clinical investigation, 2016; 126(1): 195-206.
Bhate Amruta, Parker Darren J, Bebee Thomas W, Ahn Jaegyoon, Arif Waqar, Rashan Edrees H, Chorghade Sandip, Chau Anthony, Lee Jae-Hyung, Anakk Sayeepriyadarshini, Carstens Russ P, Xiao Xinshu, Kalsotra Auinash   ESRP2 controls an adult splicing programme in hepatocytes to support postnatal liver maturation Nature communications, 2015; 6(24): 8768.
Ahn Jaegyoon, Xiao Xinshu   RASER: reads aligner for SNPs and editing sites of RNA Bioinformatics (Oxford, England), 2015; 31(24): 3906-13.
Zhang Qing, Xiao Xinshu   Genome sequence-independent identification of RNA editing sites Nature methods, 2015; 12(4): 347-50.
Bahn Jae Hoon, Ahn Jaegyoon, Lin Xianzhi, Zhang Qing, Lee Jae-Hyung, Civelek Mete, Xiao Xinshu   Genomic analysis of ADAR1 binding and its involvement in multiple RNA processing pathways Nature communications, 2015; 6(6): 6355.
Li Ziwei, Yu Juehua, Hosohama Linzi, Nee Kevin, Gkountela Sofia, Chaudhari Sonal, Cass Ashley A, Xiao Xinshu, Clark Amander T   The Sm protein methyltransferase PRMT5 is not required for primordial germ cell specification in mice The EMBO journal, 2015; 34(6): 748-58.
Lin Xianzhi, Lo Hsien-Chun, Wong David T W, Xiao Xinshu   Noncoding RNAs in human saliva as potential disease biomarkers Frontiers in genetics, 2015; 6(1): 175.
Romay Milagros C, Che Nam, Becker Scott N, Pouldar Delila, Hagopian Raffi, Xiao Xinshu, Lusis Aldons J, Berliner Judith A, Civelek Mete   Regulation of NF-κB signaling by oxidized glycerophospholipid and IL-1β induced miRs-21-3p and -27a-5p in human aortic endothelial cells Journal of lipid research, 2015; 56(1): 38-50.
Bahn Jae Hoon, Zhang Qing, Li Feng, Chan Tak-Ming, Lin Xianzhi, Kim Yong, Wong David T W, Xiao Xinshu   The landscape of microRNA, Piwi-interacting RNA, and circular RNA in human saliva Clinical chemistry, 2015; 61(1): 221-30.
Xu Yilin, Gao Xin D, Lee Jae-Hyung, Huang Huilin, Tan Haiyan, Ahn Jaegyoon, Reinke Lauren M, Peter Marcus E, Feng Yue, Gius David, Siziopikou Kalliopi P, Peng Junmin, Xiao Xinshu, Cheng Chonghui   Cell type-restricted activity of hnRNPM promotes breast cancer metastasis via regulating alternative splicing Genes & development, 2014; 28(11): 1191-203.
Xiao Xinshu Grace, Touma Marlin, Wang Yibin   Decoding the noncoding transcripts in human heart failure Circulation, 2014; 129(9): 958-60.
Lee Jae-Hyung, Ang Jason K, Xiao Xinshu   Analysis and design of RNA sequencing experiments for identifying RNA editing and other single-nucleotide variants RNA (New York, N.Y.), 2013; 19(6): 725-32.
Chan Tak-Ming, Lo Leung-Yau, Sze-To Ho-Yin, Leung Kwong-Sak, Xiao Xinshu, Wong Man-Hon   Modeling associated protein-DNA pattern discovery with unified scores IEEE/ACM transactions on computational biology and bioinformatics / IEEE, ACM, 2013; 10(3): 696-707.
Wang Yang, Xiao Xinshu, Zhang Jianming, Choudhury Rajarshi, Robertson Alex, Li Kai, Ma Meng, Burge Christopher B, Wang Zefeng   A complex network of factors with overlapping affinities represses splicing through intronic elements Nature structural & molecular biology, 2013; 20(1): 36-45.
Bass Brenda, Hundley Heather, Li Jin Billy, Peng Zhiyu, Pickrell Joe, Xiao Xinshu Grace, Yang Li   The difficult calls in RNA editing. Interviewed by H Craig Mak Nature biotechnology, 2012; 30(12): 1207-9.
Wang Yang, Ma Meng, Xiao Xinshu, Wang Zefeng   Intronic splicing enhancers, cognate splicing factors and context-dependent regulation rules Nature structural & molecular biology, 2012; 19(10): 1044-52.
Anderson Erik S, Lin Chia-Ho, Xiao Xinshu, Stoilov Peter, Burge Christopher B, Black Douglas L   The cardiotonic steroid digitoxin regulates alternative splicing through depletion of the splicing factors SRSF3 and TRA2B RNA (New York, N.Y.), 2012; 18(5): 1041-9.
Li Gang, Bahn Jae Hoon, Lee Jae-Hyung, Peng Guangdun, Chen Zugen, Nelson Stanley F, Xiao Xinshu   Identification of allele-specific alternative mRNA processing via transcriptome sequencing Nucleic acids research, 2012; 18(5): .
Bahn Jae Hoon, Lee Jae-Hyung, Li Gang, Greer Christopher, Peng Guangdun, Xiao Xinshu   Accurate identification of A-to-I RNA editing in human by transcriptome sequencing Genome research, 2012; 22(1): 142-50.
Gomez Gustavo, Lee Jae-Hyung, Veldman Matthew B, Lu Jing, Xiao Xinshu, Lin Shuo   Identification of vascular and hematopoietic genes downstream of etsrp by deep sequencing in zebrafish PloS one, 2012; 7(3): e31658.
Lee Jae-Hyung, Gao Chen, Peng Guangdun, Greer Christopher, Ren Shuxun, Wang Yibin, Xiao Xinshu   Analysis of transcriptome complexity through RNA sequencing in normal and failing murine hearts Circulation research, 2011; 109(12): 1332-41.
Xiao Xinshu, Lee Jae-Hyung   Systems analysis of alternative splicing and its regulation Wiley interdisciplinary reviews. Systems biology and medicine, 2011; 2(5): 550-65.
Puppione Donald L, Ryan Christopher M, Bassilian Sara, Souda Puneet, Xiao Xinshu, Ryder Oliver A, Whitelegge Julian P   Detection of two distinct forms of apoC-I in great apes Comparative biochemistry and physiology. Part D, Genomics & proteomics, 2010; 5(1): 73-9.
Xiao X, Wang Z, Jang M, Nutiu R, Wang ET, Burge CB   Splice site strength-dependent activity and genetic buffering by poly-G runs, Nature Structural & Molecular Biology, 2009; 16(10): 1094-1100.
Kalsotra Auinash, Xiao Xinshu, Ward Amanda J, Castle John C, Johnson Jason M, Burge Christopher B, Cooper Thomas A   A postnatal switch of CELF and MBNL proteins reprograms alternative splicing in the developing heart Proceedings of the National Academy of Sciences of the United States of America, 2008; 105(51): 20333-8.
Xiao Xinshu, Wang Zefeng, Jang Minyoung, Burge Christopher B   Coevolutionary networks of splicing cis-regulatory elements Proceedings of the National Academy of Sciences of the United States of America, 2007; 104(47): 18583-8.
Calarco John A, Xing Yi, Cáceres Mario, Calarco Joseph P, Xiao Xinshu, Pan Qun, Lee Christopher, Preuss Todd M, Blencowe Benjamin J   Global analysis of alternative splicing differences between humans and chimpanzees Genes & development, 2007; 21(22): 2963-75.
Stadler Michael B, Shomron Noam, Yeo Gene W, Schneider Aniket, Xiao Xinshu, Burge Christopher B   Inference of splicing regulatory activities by sequence neighborhood analysis PLoS genetics, 2006; 2(11): e191.
Wang Zefeng, Xiao Xinshu, Van Nostrand Eric, Burge Christopher B   General and specific functions of exonic splicing silencers in splicing control Molecular cell, 2006; 23(1): 61-70.
Wang Zhihua, Zhang Xiao-Jing, Ji Yan-Xiao, Zhang Peng, Deng Ke-Qiong, Gong Jun, Ren Shuxun, Wang Xinghua, Chen Iris, Wang He, Gao Chen, Yokota Tomohiro, Ang Yen Sin, Li Shen, Cass Ashley, Vondriska Thomas M, Li Guangping, Deb Arjun, Srivastava Deepak, Yang Huang-Tian, Xiao Xinshu, Li Hongliang, Wang Yibin   The long noncoding RNA Chaer defines an epigenetic checkpoint in cardiac hypertrophy Nature medicine, 2016; 22(10): 1131-1139.
Hasin-Brumshtein Yehudit, Khan Arshad H, Hormozdiari Farhad, Pan Calvin, Parks Brian W, Petyuk Vladislav A, Piehowski Paul D, Brümmer Anneke, Pellegrini Matteo, Xiao Xinshu, Eskin Eleazar, Smith Richard D, Lusis Aldons J, Smith Desmond J   Hypothalamic transcriptomes of 99 mouse strains reveal trans eQTL hotspots, splicing QTLs and novel non-coding genes eLife, 2016; 5(10): 1131-1139.
Arefeen Ashraful, Xiao Xinshu, Jiang Tao   DeepPASTA: deep neural network based polyadenylation site analysis Bioinformatics (Oxford, England), 2019; .
Meng Qingying, Ying Zhe, Noble Emily, Zhao Yuqi, Agrawal Rahul, Mikhail Andrew, Zhuang Yumei, Tyagi Ethika, Zhang Qing, Lee Jae-Hyung, Morselli Marco, Orozco Luz, Guo Weilong, Kilts Tina M, Zhu Jun, Zhang Bin, Pellegrini Matteo, Xiao Xinshu, Young Marian F, Gomez-Pinilla Fernando, Yang Xia   Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders EBioMedicine, 2016; 7(21): 157-66.
Sun Haipeng, Olson Kristine C, Gao Chen, Prosdocimo Domenick A, Zhou Meiyi, Wang Zhihua, Jeyaraj Darwin, Youn Ji-Youn, Ren Shuxun, Liu Yunxia, Rau Christoph D, Shah Svati, Ilkayeva Olga, Gui Wen-Jun, William Noelle S, Wynn R Max, Newgard Christopher B, Cai Hua, Xiao Xinshu, Chuang David T, Schulze Paul Christian, Lynch Christopher, Jain Mukesh K, Wang Yibin   Catabolic Defect of Branched-Chain Amino Acids Promotes Heart Failure Circulation, 2016; 133(21): 2038-49.
Yang Ei-Wen, Bahn Jae Hoon, Hsiao Esther Yun-Hua, Tan Boon Xin, Sun Yiwei, Fu Ting, Zhou Bo, Van Nostrand Eric L, Pratt Gabriel A, Freese Peter, Wei Xintao, Quinones-Valdez Giovanni, Urban Alexander E, Graveley Brenton R, Burge Christopher B, Yeo Gene W, Xiao Xinshu   Allele-specific binding of RNA-binding proteins reveals functional genetic variants in the RNA Nature communications, 2019; 10(1): 1338.
Quinones-Valdez Giovanni, Tran Stephen S, Jun Hyun-Ik, Bahn Jae Hoon, Yang Ei-Wen, Zhan Lijun, Brümmer Anneke, Wei Xintao, Van Nostrand Eric L, Pratt Gabriel A, Yeo Gene W, Graveley Brenton R, Xiao Xinshu   Regulation of RNA editing by RNA-binding proteins in human cells Communications biology, 2019; 2(1): 19.
Cheung Rocky, Insigne Kimberly D, Yao David, Burghard Christina P, Wang Jeffrey, Hsiao Yun-Hua E, Jones Eric M, Goodman Daniel B, Xiao Xinshu, Kosuri Sriram   A Multiplexed Assay for Exon Recognition Reveals that an Unappreciated Fraction of Rare Genetic Variants Cause Large-Effect Splicing Disruptions Molecular cell, 2019; 73(1): 183-194.e8.
Tran Stephen S, Jun Hyun-Ik, Bahn Jae Hoon, Azghadi Adel, Ramaswami Gokul, Van Nostrand Eric L, Nguyen Thai B, Hsiao Yun-Hua E, Lee Changhoon, Pratt Gabriel A, Martínez-Cerdeño Verónica, Hagerman Randi J, Yeo Gene W, Geschwind Daniel H, Xiao Xinshu   Widespread RNA editing dysregulation in brains from autistic individuals Nature neuroscience, 2019; 22(1): 25-36.
Harvey Samuel E, Xu Yilin, Lin Xiaodan, Gao Xin D, Qiu Yushan, Ahn Jaegyoon, Xiao Xinshu, Cheng Chonghui   Coregulation of alternative splicing by hnRNPM and ESRP1 during EMT RNA (New York, N.Y.), 2018; 24(10): 1326-1338.
Arefeen Ashraful, Liu Juntao, Xiao Xinshu, Jiang Tao   TAPAS: tool for alternative polyadenylation site analysis Bioinformatics (Oxford, England), 2018; 34(15): 2521-2529.
Li Feng, Kaczor-Urbanowicz Karolina Elżbieta, Sun Jie, Majem Blanca, Lo Hsien-Chun, Kim Yong, Koyano Kikuye, Rao Shannon Liu, Kang So Young, Kim Su Mi, Kim Kyoung-Mee, Kim Sung, Chia David, Elashoff David, Grogan Tristan R, Xiao Xinshu, Wong David T W   Characterization of Human Salivary Extracellular RNA by Next-generation Sequencing Clinical chemistry, 2018; 64(7): 1085-1095.
Hsiao Yun-Hua Esther, Bahn Jae Hoon, Yang Yun, Lin Xianzhi, Tran Stephen, Yang Ei-Wen, Quinones-Valdez Giovanni, Xiao Xinshu   RNA editing in nascent RNA affects pre-mRNA splicing Genome research, 2018; 28(6): 812-823.
Ohashi Minori, Korsakova Elena, Allen Denise, Lee Peiyee, Fu Kai, Vargas Benni S, Cinkornpumin Jessica, Salas Carlos, Park Jenny C, Germanguz Igal, Langerman Justin, Chronis Contantinos, Kuoy Edward, Tran Stephen, Xiao Xinshu, Pellegrini Matteo, Plath Kathrin, Lowry William E   Loss of MECP2 Leads to Activation of P53 and Neuronal Senescence Stem cell reports, 2018; 10(5): 1453-1463.
Burkett Zachary Daniel, Day Nancy F, Kimball Todd Haswell, Aamodt Caitlin M, Heston Jonathan B, Hilliard Austin T, Xiao Xinshu, White Stephanie A   FoxP2 isoforms delineate spatiotemporal transcriptional networks for vocal learning in the zebra finch eLife, 2018; 7(5): 1453-1463.
Kaczor-Urbanowicz Karolina Elzbieta, Kim Yong, Li Feng, Galeev Timur, Kitchen Rob R, Gerstein Mark, Koyano Kikuye, Jeong Sung-Hee, Wang Xiaoyan, Elashoff David, Kang So Young, Kim Su Mi, Kim Kyoung, Kim Sung, Chia David, Xiao Xinshu, Rozowsky Joel, Wong David T W   Novel approaches for bioinformatic analysis of salivary RNA sequencing data for development Bioinformatics (Oxford, England), 2018; 34(1): 1-8.
Brümmer Anneke, Yang Yun, Chan Tracey W, Xiao Xinshu   Structure-mediated modulation of mRNA abundance by A-to-I editing Nature communications, 2017; 8(1): 1255.
Yang Yun, Fan Xiaojuan, Mao Miaowei, Song Xiaowei, Wu Ping, Zhang Yang, Jin Yongfeng, Yang Yi, Chen Ling-Ling, Wang Yang, Wong Catherine Cl, Xiao Xinshu, Wang Zefeng   Extensive translation of circular RNAs driven by N Cell research, 2017; 27(5): 626-641.
Touma Marlin, Kang Xuedong, Zhao Yan, Cass Ashley A, Gao Fuying, Biniwale Reshma, Coppola Giovanni, Xiao Xinshu, Reemtsen Brian, Wang Yibin   Decoding the Long Noncoding RNA During Cardiac Maturation: A Roadmap for Functional Discovery Circulation. Cardiovascular genetics, 2016; 9(5): 395-407.
Das Saumya, Das Saumya, Ansel K Mark, Bitzer Markus, Breakefield Xandra O, Charest Alain, Galas David J, Gerstein Mark B, Gupta Mihir, Milosavljevic Aleksandar, McManus Michael T, Patel Tushar, Raffai Robert L, Rozowsky Joel, Roth Matthew E, Saugstad Julie A, Van Keuren-Jensen Kendall, Weaver Alissa M, Laurent Louise C   The Extracellular RNA Communication Consortium: Establishing Foundational Knowledge and Technologies for Extracellular RNA Research Cell, 2019; 177(2): 231-242.