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Wen Xue PhD

TitleAssistant Professor
InstitutionUniversity of Massachusetts Medical School
DepartmentRNA Therapeutics Institute
AddressUniversity of Massachusetts Medical School
368 Plantation Street, Shermann Center
Worcester MA 01605
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    Other Positions
    InstitutionUMMS - School of Medicine
    DepartmentProgram in Molecular Medicine

    InstitutionUMMS - School of Medicine
    DepartmentRNA Therapeutics Institute

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentBiochemistry and Molecular Pharmacology

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentCancer Biology

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentInterdisciplinary Graduate Program


    Collapse Biography 
    Collapse education and training
    Nanjing University, Nanjing, , ChinaBSBiochemistry
    Nanjing University, Nanjing, , ChinaMSBiochemistry
    State University of New York, Stony Brook, Stony Brook, NY, United StatesPHDBiochemistry
    Collapse awards and honors
    2014 - 2017Pathway to independence award 4R00CA169512-03, NIH
    2015 - 2016Scientific Merit Award, the Lung Cancer Research Foundation
    2015 - 2016Worcester Foundation Grant, Worcester Foundation
    2015 - 2016President’s Science and Technology (S&T) Fund , UMass
    2016 - 2020Research Scholars Grant , American Cancer Society
    2015Session co-chair, International Liver Cancer Association (ILCA) annual meeting
    2016 - 2021P01HL131471, NHLBI/NIH
    2016 - 2021NIH Director’s New Innovator Award, NIH
    2016 - 2018Research fund, the Lung Cancer Research Foundation
    2016 - 2018Pediatric Cancer Grant , Hyundai Hope On Wheels

    Collapse Overview 
    Collapse overview

    My lab will develop genetic models of liver and lung cancer using small RNA tools, such as RNAi-mediated silencing and CRISPR/Cas9-mediated genome editing. The CRISPR/Cas9 system allows us to quickly generate somatic loss-of-function mutations in tumor suppressor genes or gain-of-function mutations in oncogenes. Our approach presents a new avenue for rapid development of cancer models, functional genomics, and proof-of-concept targeted cancer therapy. My laboratory will engage in the following areas of research over the next few years:


    Discover and correct liver cancer genes using CRISPR-mediated genome editing


    Many candidate cancer genes are being discovered through cancer genome-sequencing efforts, and simple genetic methods are needed to validate candidate cancer genes in vivo. CRISPR/Cas genome-editing has been successfully used in many organisms, including mouse and human cells. We will use in vivo CRISPR/Cas-mediated genome editing tools to discover, validate, and correct liver cancer genes in the mouse. To identify potential liver cancer therapeutic targets, we will devise novel CRISPR strategies to delete candidate oncogenes and test the effect on liver cancer progression. Because our approach allows us to perform genetic tests without breeding mice, our approach will speed up cancer gene discovery and drug target validation for liver cancer.


    Characterize response and resistance to KRAS inhibition using in vivo RNAi and genome editing


    KRAS is mutated in >30% of lung cancer. While most studies in the literature use inducible Kras cDNA, conditional shRNA system allows knockdown of endogenous levels of Kras in vivo, offering a more physiologic model of Kras inhibition. We will model the response and resistance to Kras inhibition in mouse models using lentiviral-based tet-on shRNA in the lung. Our recent studies show that after long-term Kras inhibition by RNAi, Kras-driven tumors relapse and become Kras-independent. We will explore the molecular basis of resistance to Kras inhibition using gene expression profiling. To completely delete the oncogenic KRAS gene and compare the phenotype with RNAi-mediated knockdown, we plan to use CRISPR to generate floxed KRAS conditional knockout alleles in lung cancer cell lines. These small RNA-based experiments will generate in vivo and in vitro platforms to uncover important KRAS biology.


    Investigate oncogenic and tumor suppressor miRNA networks in lung cancer


    MicroRNAs (miRNAs) are small, non-coding RNAs that regulate mRNA translation or stability. Delineating miRNA networks can identify new miRNAs and miRNA antagonists for lung cancer treatment. We will cross-compare human lung adenocarcinoma miRNA expression profiles and cancer genome copy number analyses from TCGA (the Cancer Genome Atlas) to identify candidate miRNAs that drive or suppress tumor formation. We will use tet-on miRNA expression system to conditionally express miRNA at various stages of tumor progression and study the impact on tumor growth in vivo. Together, these studies will unveil miRNA networks in cancer using genetic tools.  



    Collapse Rotation Projects


    Our lab uses CRISPR tools to speed up cancer gene discovery and disease gene repair. Rotation projects are available to explore experimental techniques such as molecular cloning of CRISPR plasmids, measuring genome-editing efficiency, dissecting mice, and processing of mouse tumor/tissue for histology.



    Collapse Post Docs


    We are looking for postdoc candidates with experience in cancer biology, mouse models and genome-engineering. Please email CV and 3 letters of recommendation to Wen.Xue@umassmed.edu.




    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Song CQ, Xue W. CRISPR-Cas-related technologies in basic and translational liver research. Nat Rev Gastroenterol Hepatol. 2018 Feb 14. PMID: 29443117.
      View in: PubMed
    2. Yin H, Song CQ, Suresh S, Kwan SY, Wu Q, Walsh S, Ding J, Bogorad RL, Zhu LJ, Wolfe SA, Koteliansky V, Xue W, Langer R, Anderson DG. Partial DNA-guided Cas9 enables genome editing with reduced off-target activity. Nat Chem Biol. 2018 Mar; 14(3):311-316. PMID: 29377001.
      View in: PubMed
    3. Yin H, Song CQ, Suresh S, Wu Q, Walsh S, Rhym LH, Mintzer E, Bolukbasi MF, Zhu LJ, Kauffman K, Mou H, Oberholzer A, Ding J, Kwan SY, Bogorad RL, Zatsepin T, Koteliansky V, Wolfe SA, Xue W, Langer R, Anderson DG. Structure-guided chemical modification of guide RNA enables potent non-viral in vivo genome editing. Nat Biotechnol. 2017 Nov 13. PMID: 29131148.
      View in: PubMed
    4. Dang H, Takai A, Forgues M, Pomyen Y, Mou H, Xue W, Ray D, Ha KCH, Morris QD, Hughes TR, Wang XW. Oncogenic Activation of the RNA Binding Protein NELFE and MYC Signaling in Hepatocellular Carcinoma. Cancer Cell. 2017 Jul 10; 32(1):101-114.e8. PMID: 28697339.
      View in: PubMed
    5. Mou H, Smith JL, Peng L, Yin H, Moore J, Zhang XO, Song CQ, Sheel A, Wu Q, Ozata DM, Li Y, Anderson DG, Emerson CP, Sontheimer EJ, Moore MJ, Weng Z, Xue W. CRISPR/Cas9-mediated genome editing induces exon skipping by alternative splicing or exon deletion. Genome Biol. 2017 Jun 14; 18(1):108. PMID: 28615073.
      View in: PubMed
    6. Tammela T, Sanchez-Rivera FJ, Cetinbas NM, Wu K, Joshi NS, Helenius K, Park Y, Azimi R, Kerper NR, Wesselhoeft RA, Gu X, Schmidt L, Cornwall-Brady M, Yilmaz ÖH, Xue W, Katajisto P, Bhutkar A, Jacks T. A Wnt-producing niche drives proliferative potential and progression in lung adenocarcinoma. Nature. 2017 05 18; 545(7654):355-359. PMID: 28489818.
      View in: PubMed
    7. Mou H, Moore J, Malonia SK, Li Y, Ozata DM, Hough S, Song CQ, Smith JL, Fischer A, Weng Z, Green MR, Xue W. Genetic disruption of oncogenic Kras sensitizes lung cancer cells to Fas receptor-mediated apoptosis. Proc Natl Acad Sci U S A. 2017 Mar 20. PMID: 28320962.
      View in: PubMed
    8. Song CQ, Li Y, Mou H, Moore J, Park A, Pomyen Y, Hough S, Kennedy Z, Fischer A, Yin H, Anderson DG, Conte D, Zender L, Wang XW, Thorgeirsson S, Weng Z, Xue W. Genome-wide CRISPR Screen Identifies Regulators of MAPK as Suppressors of Liver Tumors in Mice. Gastroenterology. 2016 Dec 09. PMID: 27956228.
      View in: PubMed
    9. Sheel A, Xue W. Genomic Amplifications Cause False Positives in CRISPR Screens. Cancer Discov. 2016 Aug; 6(8):824-6. PMID: 27485003.
      View in: PubMed
    10. Akama-Garren EH, Joshi NS, Tammela T, Chang GP, Wagner BL, Lee DY, Rideout WM, Papagiannakopoulos T, Xue W, Jacks T. A Modular Assembly Platform for Rapid Generation of DNA Constructs. Sci Rep. 2016 Feb 18; 6:16836. PMID: 26887506.
      View in: PubMed
    11. Yin H, Song CQ, Dorkin JR, Zhu LJ, Li Y, Wu Q, Park A, Yang J, Suresh S, Bizhanova A, Gupta A, Bolukbasi MF, Walsh S, Bogorad RL, Gao G, Weng Z, Dong Y, Koteliansky V, Wolfe SA, Langer R, Xue W, Anderson DG. Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo. Nat Biotechnol. 2016 Mar; 34(3):328-33. PMID: 26829318.
      View in: PubMed
    12. Yin H, Bogorad RL, Barnes C, Walsh S, Zhuang I, Nonaka H, Ruda V, Kuchimanchi S, Nechev L, Akinc A, Xue W, Zerial M, Langer R, Anderson DG, Koteliansky V. RNAi-nanoparticulate manipulation of gene expression as a new functional genomics tool in the liver. J Hepatol. 2016 Apr; 64(4):899-907. PMID: 26658687.
      View in: PubMed
    13. Wang D, Mou H, Li S, Li Y, Hough S, Tran K, Li J, Yin H, Anderson DG, Sontheimer EJ, Weng Z, Gao G, Xue W. Adenovirus-Mediated Somatic Genome Editing of Pten by CRISPR/Cas9 in Mouse Liver in Spite of Cas9-Specific Immune Responses. Hum Gene Ther. 2015 Jul; 26(7):432-42. PMID: 26086867.
      View in: PubMed
    14. Mou H, Kennedy Z, Anderson DG, Yin H, Xue W. Precision cancer mouse models through genome editing with CRISPR-Cas9. Genome Med. 2015; 7(1):53. PMID: 26060510.
      View in: PubMed
    15. Li Y, Park AI, Mou H, Colpan C, Bizhanova A, Akama-Garren E, Joshi N, Hendrickson EA, Feldser D, Yin H, Anderson DG, Jacks T, Weng Z, Xue W. A versatile reporter system for CRISPR-mediated chromosomal rearrangements. Genome Biol. 2015 May 28; 16:111. PMID: 26018130.
      View in: PubMed
    16. Khan OF, Zaia EW, Jhunjhunwala S, Xue W, Cai W, Yun DS, Barnes CM, Dahlman JE, Dong Y, Pelet JM, Webber MJ, Tsosie JK, Jacks TE, Langer R, Anderson DG. Dendrimer-Inspired Nanomaterials for the in Vivo Delivery of siRNA to Lung Vasculature. Nano Lett. 2015 May 13; 15(5):3008-16. PMID: 25789998.
      View in: PubMed
    17. Li J, Chanrion M, Sawey E, Wang T, Chow E, Tward A, Su Y, Xue W, Lucito R, Zender L, Lowe SW, Bishop JM, Powers S. Reciprocal interaction of Wnt and RXR-a pathways in hepatocyte development and hepatocellular carcinoma. PLoS One. 2015; 10(3):e0118480. PMID: 25738607.
      View in: PubMed
    18. Sánchez-Rivera FJ, Papagiannakopoulos T, Romero R, Tammela T, Bauer MR, Bhutkar A, Joshi NS, Subbaraj L, Bronson RT, Xue W, Jacks T. Rapid modelling of cooperating genetic events in cancer through somatic genome editing. Nature. 2014 Dec 18; 516(7531):428-31. PMID: 25337879.
      View in: PubMed
    19. Xue W, Dahlman JE, Tammela T, Khan OF, Sood S, Dave A, Cai W, Chirino LM, Yang GR, Bronson R, Crowley DG, Sahay G, Schroeder A, Langer R, Anderson DG, Jacks T. Small RNA combination therapy for lung cancer. Proc Natl Acad Sci U S A. 2014 Aug 26; 111(34):E3553-61. PMID: 25114235.
      View in: PubMed
    20. Xue W, Chen S, Yin H, Tammela T, Papagiannakopoulos T, Joshi NS, Cai W, Yang G, Bronson R, Crowley DG, Zhang F, Anderson DG, Sharp PA, Jacks T. CRISPR-mediated direct mutation of cancer genes in the mouse liver. Nature. 2014 Oct 16; 514(7522):380-4. PMID: 25119044.
      View in: PubMed
    21. Tschaharganeh DF, Xue W, Calvisi DF, Evert M, Michurina TV, Dow LE, Banito A, Katz SF, Kastenhuber ER, Weissmueller S, Huang CH, Lechel A, Andersen JB, Capper D, Zender L, Longerich T, Enikolopov G, Lowe SW. p53-dependent Nestin regulation links tumor suppression to cellular plasticity in liver cancer. Cell. 2014 Jul 31; 158(3):579-92. PMID: 25083869.
      View in: PubMed
    22. Shao DD, Xue W, Krall EB, Bhutkar A, Piccioni F, Wang X, Schinzel AC, Sood S, Rosenbluh J, Kim JW, Zwang Y, Roberts TM, Root DE, Jacks T, Hahn WC. KRAS and YAP1 converge to regulate EMT and tumor survival. Cell. 2014 Jul 3; 158(1):171-84. PMID: 24954536.
      View in: PubMed
    23. Yin H, Xue W, Chen S, Bogorad RL, Benedetti E, Grompe M, Koteliansky V, Sharp PA, Jacks T, Anderson DG. Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype. Nat Biotechnol. 2014 Jun; 32(6):551-3. PMID: 24681508.
      View in: PubMed
    24. Xue W, Kitzing T, Roessler S, Zuber J, Krasnitz A, Schultz N, Revill K, Weissmueller S, Rappaport AR, Simon J, Zhang J, Luo W, Hicks J, Zender L, Wang XW, Powers S, Wigler M, Lowe SW. A cluster of cooperating tumor-suppressor gene candidates in chromosomal deletions. Proc Natl Acad Sci U S A. 2012 May 22; 109(21):8212-7. PMID: 22566646.
      View in: PubMed
    25. Oliver TG, Meylan E, Chang GP, Xue W, Burke JR, Humpton TJ, Hubbard D, Bhutkar A, Jacks T. Caspase-2-mediated cleavage of Mdm2 creates a p53-induced positive feedback loop. Mol Cell. 2011 Jul 8; 43(1):57-71. PMID: 21726810.
      View in: PubMed
    26. Xue W, Meylan E, Oliver TG, Feldser DM, Winslow MM, Bronson R, Jacks T. Response and resistance to NF-?B inhibitors in mouse models of lung adenocarcinoma. Cancer Discov. 2011 Aug; 1(3):236-47. PMID: 21874163.
      View in: PubMed
    27. Liu LX, Lee NP, Chan VW, Xue W, Zender L, Zhang C, Mao M, Dai H, Wang XL, Xu MZ, Lee TK, Ng IO, Chen Y, Kung HF, Lowe SW, Poon RT, Wang JH, Luk JM. Targeting cadherin-17 inactivates Wnt signaling and inhibits tumor growth in liver carcinoma. Hepatology. 2009 Nov; 50(5):1453-63. PMID: 19676131.
      View in: PubMed
    28. Krizhanovsky V, Xue W, Zender L, Yon M, Hernando E, Lowe SW. Implications of cellular senescence in tissue damage response, tumor suppression, and stem cell biology. Cold Spring Harb Symp Quant Biol. 2008; 73:513-22. PMID: 19150958.
      View in: PubMed
    29. Zender L, Xue W, Zuber J, Semighini CP, Krasnitz A, Ma B, Zender P, Kubicka S, Luk JM, Schirmacher P, McCombie WR, Wigler M, Hicks J, Hannon GJ, Powers S, Lowe SW. An oncogenomics-based in vivo RNAi screen identifies tumor suppressors in liver cancer. Cell. 2008 Nov 28; 135(5):852-64. PMID: 19012953.
      View in: PubMed
    30. Gyrd-Hansen M, Darding M, Miasari M, Santoro MM, Zender L, Xue W, Tenev T, da Fonseca PC, Zvelebil M, Bujnicki JM, Lowe S, Silke J, Meier P. IAPs contain an evolutionarily conserved ubiquitin-binding domain that regulates NF-kappaB as well as cell survival and oncogenesis. Nat Cell Biol. 2008 Nov; 10(11):1309-17. PMID: 18931663.
      View in: PubMed
    31. Burgess DJ, Doles J, Zender L, Xue W, Ma B, McCombie WR, Hannon GJ, Lowe SW, Hemann MT. Topoisomerase levels determine chemotherapy response in vitro and in vivo. Proc Natl Acad Sci U S A. 2008 Jul 1; 105(26):9053-8. PMID: 18574145.
      View in: PubMed
    32. Xue W, Krasnitz A, Lucito R, Sordella R, Vanaelst L, Cordon-Cardo C, Singer S, Kuehnel F, Wigler M, Powers S, Zender L, Lowe SW. DLC1 is a chromosome 8p tumor suppressor whose loss promotes hepatocellular carcinoma. Genes Dev. 2008 Jun 1; 22(11):1439-44. PMID: 18519636.
      View in: PubMed
    33. He L, He X, Lim LP, de Stanchina E, Xuan Z, Liang Y, Xue W, Zender L, Magnus J, Ridzon D, Jackson AL, Linsley PS, Chen C, Lowe SW, Cleary MA, Hannon GJ. A microRNA component of the p53 tumour suppressor network. Nature. 2007 Jun 28; 447(7148):1130-4. PMID: 17554337.
      View in: PubMed
    34. Xue W, Zender L, Miething C, Dickins RA, Hernando E, Krizhanovsky V, Cordon-Cardo C, Lowe SW. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature. 2007 Feb 8; 445(7128):656-60. PMID: 17251933.
      View in: PubMed
    35. Lakshmi B, Hall IM, Egan C, Alexander J, Leotta A, Healy J, Zender L, Spector MS, Xue W, Lowe SW, Wigler M, Lucito R. Mouse genomic representational oligonucleotide microarray analysis: detection of copy number variations in normal and tumor specimens. Proc Natl Acad Sci U S A. 2006 Jul 25; 103(30):11234-9. PMID: 16844783.
      View in: PubMed
    36. Zender L, Spector MS, Xue W, Flemming P, Cordon-Cardo C, Silke J, Fan ST, Luk JM, Wigler M, Hannon GJ, Mu D, Lucito R, Powers S, Lowe SW. Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach. Cell. 2006 Jun 30; 125(7):1253-67. PMID: 16814713.
      View in: PubMed
    37. Zender L, Xue W, Cordón-Cardo C, Hannon GJ, Lucito R, Powers S, Flemming P, Spector MS, Lowe SW. Generation and analysis of genetically defined liver carcinomas derived from bipotential liver progenitors. Cold Spring Harb Symp Quant Biol. 2005; 70:251-61. PMID: 16869761.
      View in: PubMed
    38. Xue W, Wang J, Shen Z, Zhu H. Enrichment of transcriptional regulatory sites in non-coding genomic region. Bioinformatics. 2004 Mar 1; 20(4):569-75. PMID: 14990453.
      View in: PubMed
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