Han Xu, Ph.D.
Department of Epigenetics and Molecular Carcinogenesis, Division of Division of Discovery Science
Present Title & Affiliation
Primary Appointment
Associate Professor, Department of Epigenetics and Molecular Carcinogenesis, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center, Houston, TX
Dual/Joint/Adjunct Appointment
Faculty Member, Graduate School of Biomedical Sciences (GSBS), The University of Texas Health Science Center, Houston, TX
Research Interests
I am interested in developing computational algorithms for the design and analysis of high-throughput biological experiments, with a focus on applications in the field of transcriptional and epigenetic regulation. The advent of Next-Generation Sequencing has facilitated the development of a number of high-throughput biotechnologies in the past decade, which have greatly accelerated biomedical research. Innovative computational methods are in demand, not only for standardized data processing, but also for rational design and unbiased interpretation of these experiments. We have developed a series of bioinformatics tools for applications with ChIP-seq, DNase-seq, RNA-seq, and 3D chromatin interaction experiments. These tools have enabled in-depth collaborations leading to the elucidation of transcriptional and epigenetic regulatory mechanisms in cancer cells and embryonic stem cells. My current research interest is mainly on the optimization, design, and analysis of CRISPR-based genetic or epigenetic perturbation screens. We are developing machine-learning and statistical methods to boost the performance of CRISPR screens, and are using these approaches for systematic functional characterization of coding and non-coding genomic regions. We are also developing novel algorithms to integrate information from CRISPR screens and other heterogeneous “-omic” datasets. Working with molecular biologists and clinical researchers, my group combines our computational expertise with cutting-edge biotechnologies to address fundamental questions in cancer epigenetics and to decipher the genetic and epigenetic “codes” underlying various cancer phenotypes.
Education & Training
Degree-Granting Education
| 2011 | Nanyang Technological University, Singapore, SGP, PHD, Bioinformatics |
| 1999 | Zhejiang University, Zhejiang, CHN, ME, Information Systems |
| 1996 | Zhejiang University, Zhejiang, CHN, BE, Computer Science |
Postgraduate Training
| 2010-2015 | Postdoctoral Research Fellowship, Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, MA |
Selected Publications
Peer-Reviewed Articles
- Zheng C, Wei Y, Zhang P, Lin K, He D, Teng H, Manyam G, Zhang Z, Liu W, Lee HRL, Tang X, He W, Islam N, Jain A, Chiu Y, Cao S, Diao Y, Meyer-Gauen S, Höök M, Malovannaya A, Li W, Hu M, Wang W, Xu H, Kopetz S, Chen Y. CRISPR-Cas9-based functional interrogation of unconventional translatome reveals human cancer dependency on cryptic non-canonical open reading frames. Nat Struct Mol Biol 30(12):1878-1892, 2023. e-Pub 2023. PMID: 37932451.
- Zhang L, He W, Fu R, Wang S, Chen Y, Xu H. Guide-specific loss of efficiency and off-target reduction with Cas9 variants. Nucleic Acids Res 51(18):9880-9893, 2023. PMID: 37615574.
- Xu L, Xuan H, He W, Zhang L, Huang M, Li K, Wen H, Xu H, Shi X. TAZ2 truncation confers overactivation of p300 and cellular vulnerability to HDAC inhibition. Nat Commun 14(1):5362, 2023. e-Pub 2023. PMID: 37660055.
- Zheng C, Wei Y, Zhang Q, Sun M, Wang Y, Hou J, Zhang P, Lv X, Su D, Jiang Y, Gumin J, Sahni N, Hu B, Wang W, Chen X, McGrail DJ, Zhang C, Huang S, Xu H, Chen J, Lang FF, Hu J, Chen Y. Multiomics analyses reveal DARS1-AS1/YBX1-controlled posttranscriptional circuits promoting glioblastoma tumorigenesis/radioresistance. Sci Adv 9(31):eadf3984, 2023. e-Pub 2023. PMID: 37540752.
- Zheng C, Wei Y, Zhang P, Xu L, Zhang Z, Lin K, Hou J, Lv X, Ding Y, Chiu Y, Jain A, Islam N, Malovannaya A, Wu Y, Ding F, Xu H, Sun M, Chen X, Chen Y. CRISPR/Cas9 screen uncovers functional translation of cryptic lncRNA-encoded open reading frames in human cancer. J Clin Invest 133(5), 2023. e-Pub 2023. PMID: 36856111.
- Srour N, Villarreal OD, Hardikar S, Yu Z, Preston S, Miller WH, Szewczyk MM, Barsyte-Lovejoy D, Xu H, Chen T, Del Rincón SV, Richard S. PRMT7 ablation stimulates anti-tumor immunity and sensitizes melanoma to immune checkpoint blockade. Cell Rep 38(13):110582, 2022. PMID: 35354055.
- Fu R, He W, Dou J, Villarreal OD, Bedford E, Wang H, Hou C, Zhang L, Wang Y, Ma D, Chen Y, Gao X, Depken M, Xu H. Systematic decomposition of sequence determinants governing CRISPR/Cas9 specificity. Nat Commun 13(1):474, 2022. e-Pub 2022. PMID: 35078987.
- Liao Y, Chen CH, Xiao T, de la Peña Avalos B, Dray EV, Cai C, Gao S, Shah N, Zhang Z, Feit A, Xue P, Liu Z, Yang M, Lee JH, Xu H, Li W, Mei S, Pierre RS, Shu S, Fei T, Duarte M, Zhao J, Bradner JE, Polyak K, Kantoff PW, Long H, Balk SP, Liu XS, Brown M, Xu K. Inhibition of EZH2 transactivation function sensitizes solid tumors to genotoxic stress. Proc Natl Acad Sci U S A 119(3), 2022. PMID: 35031563.
- Sun M, Wang Y, Zheng C, Wei Y, Hou J, Zhang P, He W, Lv X, Ding Y, Liang H, Hon CC, Chen X, Xu H*, Chen Y*. Systematic functional interrogation of human pseudogenes using CRISPRi. Genome Biol 22(1):240, 2021. e-Pub 2021. PMID: 34425866 (*co-senior authors).
- He W, Wang H, Wei Y, Jiang Z, Tang Y, Chen Y, Xu H. GuidePro: A multi-source ensemble predictor for prioritizing sgRNAs in CRISPR/Cas9 protein knockouts. Bioinformatics 37(1):134-136, 2021. e-Pub 2021. PMID: 33394026.
- Veazey KJ, Cheng D, Lin K, Villarreal OD, Gao G, Perez-Oquendo M, Van HT, Stratton SA, Green M, Xu H, Lu Y, Bedford MT, Santos MA. CARM1 inhibition reduces histone acetyltransferase activity causing synthetic lethality in CREBBP/EP300-mutated lymphomas. Leukemia 34(12):3269-3285, 2020. e-Pub 2020. PMID: 32576962.
- He W, Zhang L, Villarreal OD, Fu R, Bedford E, Dou J, Patel AY, Bedford MT, Shi X, Chen T, Bartholomew B, Xu H. De novo identification of essential protein domains from CRISPR-Cas9 tiling-sgRNA knockout screens. Nat Commun 10(1):4541, 2019. e-Pub 2019. PMID: 31586052.
- Gao G, Zhang L, Villarreal OD, He W, Su D, Bedford E, Moh P, Shen J, Shi X, Bedford MT*, Xu H*. PRMT1 loss sensitizes cells to PRMT5 inhibition. Nucleic Acids Res 47(10):5038-5048, 2019. PMID: 30916320 (*co-senior authors).
- Rosenbluh J*, Xu H*, Harrington W, Gill S, Wang X, Vazquez F, Root DE, Tsherniak A, Hahn WC. Complementary information derived from CRISPR Cas9 mediated gene deletion and suppression. Nat Commun 8:15403, 2017. e-Pub 2017. PMID: 28534478 (*co-first authors.
- Ma J, Köster J, Qin Q, Hu S, Li W, Chen C, Cao Q, Wang J, Mei S, Liu Q, Xu H*, Liu XS*. CRISPR-DO for genome-wide CRISPR design and optimization. Bioinformatics 32(21):3336-3338, 2016. e-Pub 2016. PMID: 27402906 (*co-senior author).
- Xu H*, Xu K*, He HH, Zang C, Chen CH, Chen Y, Qin Q, Wang S, Wang C, Hu S, Li F, Long H, Brown M, Liu XS. Integrative Analysis Reveals the Transcriptional Collaboration between EZH2 and E2F1 in the Regulation of Cancer-Related Gene Expression. Mol Cancer Res 14(2):163-72, 2016. e-Pub 2015. PMID: 26659825 (*co-first authors).
- Xu H*, Xiao T*, Chen CH, Li W, Meyer CA, Wu Q, Wu D, Cong L, Zhang F, Liu JS, Brown M, Liu XS. Sequence determinants of improved CRISPR sgRNA design. Genome Res 25(8):1147-57, 2015. e-Pub 2015. PMID: 26063738 (*co-first authors).
- Li W*, Xu H*, Xiao T, Cong L, Love MI, Zhang F, Irizarry RA, Liu JS, Brown M, Liu XS. MAGeCK enables robust identification of essential genes from genome-scale CRISPR/Cas9 knockout screens. Genome Biol 15(12):554, 2014. PMID: 25476604 (*co-first author).
- Xu H, Sung WK. Identifying differential histone modification sites from ChIP-seq data. Methods Mol Biol 802:293-303, 2012. PMID: 22130888.
- Handoko L*, Xu H*, Li G*, Ngan CY, Chew E, Schnapp M, Lee CW, Ye C, Ping JL, Mulawadi F, Wong E, Sheng J, Zhang Y, Poh T, Chan CS, Kunarso G, Shahab A, Bourque G, Cacheux-Rataboul V, Sung WK, Ruan Y, Wei CL. CTCF-mediated functional chromatin interactome in pluripotent cells. Nat Genet 43(7):630-8, 2011. e-Pub 2011. PMID: 21685913 (*co-first author).
- Xu H, Handoko L, Wei X, Ye C, Sheng J, Wei CL, Lin F, Sung WK. A signal-noise model for significance analysis of ChIP-seq with negative control. Bioinformatics 26(9):1199-204, 2010. e-Pub 2010. PMID: 20371496.
- Xu H, Wei CL, Lin F, Sung WK. An HMM approach to genome-wide identification of differential histone modification sites from ChIP-seq data. Bioinformatics 24(20):2344-9, 2008. e-Pub 2008. PMID: 18667444.
- Chen X*, Xu H*, Yuan P, Fang F, Huss M, Vega VB, Wong E, Orlov YL, Zhang W, Jiang J, Loh YH, Yeo HC, Yeo ZX, Narang V, Govindarajan KR, Leong B, Shahab A, Ruan Y, Bourque G, Sung WK, Clarke ND, Wei CL, Ng HH. Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 133(6):1106-17, 2008. PMID: 18555785 (*co-first author).
- Zhao XD*, Han X*, Chew JL, Liu J, Chiu KP, Choo A, Orlov YL, Sung WK, Shahab A, Kuznetsov VA, Bourque G, Oh S, Ruan Y, Ng HH, Wei CL. Whole-genome mapping of histone H3 Lys4 and 27 trimethylations reveals distinct genomic compartments in human embryonic stem cells. Cell Stem Cell 1(3):286-98, 2007. PMID: 18371363 (*co-first author).
Grant & Contract Support
| Title: | Recruitment of First-time, Tenure-Track Faculty - Dr. Han Xu |
| Funding Source: | Cancer Prevention & Research Institute of Texas (CPRIT) |
| Role: | Principal Investigator |
| Title: | Integrative Approaches to Identifying Epigenetic Regulatory Networks in Cancer |
| Funding Source: | University of Texas System Rising STARs Award |
| Role: | Principal Investigator |
| Title: | Transcriptional Activation by Reorganizing Chromatin |
| Funding Source: | NIH/NCI |
| Role: | Co-Investigator |
| Title: | Assessment, modeling, and prediction of CRISPR/Cas9 off-target effect |
| Funding Source: | NIH/NHGRI |
| Role: | Principal Investigator |
| Title: | Synthetic Lethality of MAT2A and MLLs in Small Cell Lung Cancer |
| Funding Source: | UTMDACC Tobacco Settlement Pilot Award |
| Role: | Principal Investigator |
Patient Reviews
CV information above last modified August 14, 2024