Wen Xue, Ph.D
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Wen Xue, Ph.D. RNA Therapeutics Institute University of Massachusetts Medical School 368 Plantation Street, AS4-2053 Worcester, MA 01605 (774) 455-3783 Fax: (508) 856-6696 [email protected] Lab Home page: http://www.umassmed.edu/xuelab/ Education Ph.D., Stony Brook University, The State University of New York, Stony Brook, NY 2004-2009 Thesis: Tumor suppressor gene networks in liver cancer Advisor: Dr. Scott Lowe M.S., Biochemistry, Nanjing University, China 2002-2004 Thesis: Transcriptional regulation in eukaryotes Advisor: Dr. Jin Wang 1998-2002 B.S., Biochemistry, Nanjing University, China Appointments Assistant Professor, RNA Therapeutics Institute, 2014-present Program of Molecular Medicine, and MCCB University of Massachusetts Medical School, Worcester, MA Postdoctoral Research 2009-2014 Koch Institute, MIT, Cambridge, MA Advisor: Dr. Tyler Jacks Honors and Awards NIH Director’s New Innovator Award 2016-2021 American Cancer Society Research Scholars Grant 2016-2020 The Lung Cancer Research Foundation Scientific Merit Award 2015 Worcester Foundation Award 2015 NCI-K99 Pathway to Independence Award 2012-2017 The Leukemia & Lymphoma Society Career Development Program Award 2011-2012 American Association for Cancer Research (AACR) Pre-doctoral Fellowship 2008-2011 Professional Memberships and Activities Member, American Society of Gene & Cell Therapy (ASGCT) 2018-present Member, American Association for Cancer Research (AACR) 2008-present Member, International Liver Cancer Association (ILCA) 2016-present Consultant, Cystic Fibrosis Foundation Therapeutics lab, Lexington, MA 2017-present Consultant, LEK consulting, Boston, MA 2018-present Ad hoc consultant for other companies 2017-present Outside Service / Peer Review Activities Editorial Board: Human Gene Therapy (2015-now), FASEB (2019-now) Guest editor: 2019 Theranostics special issue: Progress in Gene Editing Nanotheranostics Referee (ad hoc) for the following journals (>10 review per year): Nature, Nature 2014-present biotechnology, Nature Genetics, Nature Methods, Nature Materials, Cancer Cell, Cancer Discovery, Gastroenterology, Nature Communications, eLIFE, Genome Biology, Human Gene Therapy, Cancer Letters, FEBS, Trends in Cancer, Mol Therapy, etc Referee of grants for funding agencies: UPenn Orphan Disease Center Pilot Grant 2017 Educational Activities Teaching Activities (classroom hours) 2019 Instructor, UMMS Cancer Bio BBS 725, (2 hours, March)* 2018 Instructor, UMMS Foundation course, cancer module (6 hours, Oct) 2018 Instructor, UMMS Foundation course, cancer module (6 hours, Jan) 2018 Instructor, UMMS Regulatory RNA Biology (BBS 718) (2 hours) 2017 Instructor, UMMS Foundation course (6 hours) 2017 Instructor, UMMS cancer bio BBS 725 (6 hours) 2016 Instructor, UMMS Foundation course (3 hours) 2015 Instructor, UMMS Regulatory RNA Biology (BBS 718) (2 hours) 2015 Instructor, UMMS Core Course RAPS (2 hours) 2014 Instructor, UMMS Core Course RAPS (2 hours) 2014 Instructor, UMMS Ethics Course (2 hours) 2010 Instructor, MIT Advanced Undergraduate Course (15 hours) Advising, Mentoring & Supervision: Current postdoc and students: 1. Chunqing Song, Postdoc, Joint mentor with Dr. Craig Mello 2015-present 2. SuetYan Kwan, Postdoc 2016-present 3. Tingting Jiang, Postdoc 2017-present 4. Shunqing Liang, Postdoc 2018-present 5. Zachary Kennedy, Neuroscience PhD student, Joint mentor with Dr. Robert Brown 2015-present 6. Ankur Sheel, MD/PhD student (NCI F30 2018-2022) 2016-present 7. Jordan Smith, MD/PhD student (NCI F30 2019-2023, UMass T32 2017-2018) 2017-present Former postdoc and students: Haiwei Mou, Postdoc. Current: postdoc, Cold Spring Harbor Labs 2014-2018 Yingxiang Li, Visiting PhD student with Dr. Zhiping Weng. Current: Senior Bioinformatics 2015-2016 Engineer at WeGene, China Grants 2 Current NIH/NHLBI DP2HL137167 Xue 2016-2021 CRISPR-based modular therapy for precision medicine Description: To develop Cas9 delivery modules for precision genome editing Total Award: $2,512,500 (direct =$300,000 / year) PI: 25% effort NIH/NHLBI P01HL131471 Flotte 2016-2021 New Approaches to Gene Therapy for Alpha-1 Antitrypsin Deficiency Project 3: Liver-directed somatic gene correction rAAV system of regulatable Cas9/sgRNA Description: To establish a pre-clinical paradigm for CRISPR-mediated correction of AAT deficiency in the mouse Total Award: ~$2,500,000 (direct =~$300,000 / year) co-I, PI of Project 3: 20% effort American Cancer Society 129056-RSG-16-093 Xue 2016-2020 An integrative approach to study KRAS inhibition in lung cancer Description: To elucidate the function of oncogenic KRAS in lung tumor maintenance Total Award: $791,000 (direct =$165,000 / year) PI: 10% effort Lung Cancer Research Foundation Xue 2016-2019 Targeting NF-κB as an Achilles’ heel in KRAS-mutant lung cancer Description: To identify mechanisms of NF-κB signaling in lung cancer. Total Award: $150,000 PI: 1% effort UMass CCTS pilot award program Sontheimer 2018-2019 All-in-one AAV Delivery of a Compact Cas9 Ortholog in the Central Nervous System Description: To develop AAV delivery of a Compact Cas9 Ortholog Total Award: $60,000 (~$15,000 Xue lab) co-I: 5% effort NIH/NHLBI UG3HL147367 Gao/Anderson/Xue 2018-2021 Develop combinatorial non-viral and viral CRISPR delivery for lung diseases Description: To develop new CRISPR delivery toolkits for lung diseases Total Award: direct =$166,000 / year for Xue lab co-PI: 10% effort Completed (total grant, role, % effort) Hyundai Pediatric Cancer Grant (2016-2018) $250,000 PI: 10% ALS Association Robert Brown (2017-2018) $169,000 co-I: 1% NIH/NCI R00CA169512 (2014-2017) $747,000 PI: 20% UMass CCTS Pilot Project Program (2016-2017) $50,000 PI: 5% UMass President’s S&T Fund (2015-2016) $25,000 co-PI: 1% Lung Cancer Research Foundation (2015-2016) $75,000 PI: 5% Worcester Foundation (2015-2016) $35,000 PI: 1% Technology Development Patent applications: 3 Structure-guided chemical modification of guide RNA and its applications Yin H, Anderson DG, Langer R, Xue W, Song CQ PCT Application No: 16/256,003 filed on 01/24/2019 Delivery systems and kits for gene editing Yin H, Xue W, Anderson DG, Dorkin J, Jacks T. US patent No. 10,047,355, issued on 08/14/2018 Methods for in vivo genome editing Yin H, Xue W, Bogorad RL, Anderson DG, Jacks T. PCT Application No: PCT/ US2015/017246. Priority date Feb 24, 2014 Methods and products related to lung cancer US20,150,150,892 TE Jacks, W Xue, E Meylan, TG Oliver, D Feldser, M Winslow. 2015 Cooperating oncogenes in cancer US20110035814, EP2027294,WO2007139985A9 L Zender, SW Lowe, MS Spector, W Xue 2011 Oncogenomics-based rnai screen and use thereof to identify novel tumor suppressors US20100273660 L Zender, W Xue, S Powers, SW Lowe 2009 Orthotopic, controllable, and genetically tractable non-human animal model for cancer US20090022685, WO2008021393 R Dickins, GJ Hannon, SW Lowe, W Xue, L Zender 2008 Publications Please access Google Scholar. In March 2019, my H-index is 28 and total citation is 9,924. https://scholar.google.com/citations?user=oANsQ4YAAAAJ&hl=en&oi=ao A. Publications from work at UMassmed Total publications at UMass: 30 (24 primary papers including 11 corresponding + 6 reviews). A1. Peer-reviewed corresponding author (# Co-corresponding, * Co-first) 1. Mou H*, Ozata D*. Smith J*, et al, Xue W#. CRISPR-SONIC: targeted somatic oncogene knock-in enables rapid in vivo cancer modeling. Genome Medicine 2019. in press. 2. Song C-Q*, Jiang T*, et al, Liu D#, Yin H#, Xue W#. Adenine base editing in an adult mouse model of tyrosinemia. Nature Biomedical Engineering. 2019. doi.org/10.1038/s41551-019-0357-8 3. Wang D, Li J, Song C-Q, et al, Zamore PD#, Xue W#, and Gao G#. Repairing recessive compound heterozygous mutations in vivo via cas9-mediated allelic exchange. Nat Biotechnology. 2018. 36:839–842 4. Song C-Q, Wang D, et al, Terence R#, Xue W#. in vivo genome editing partially restores alpha1-antitrypsin in a murine model of AAT deficiency. Hum Gene Therapy 2018. 29 (8):853-860 5. Yin H*, Song C-Q*, et al, Xue W#, Langer R#, Anderson DG#. Partial DNA-guided Cas9 enables efficient genome editing with reduced off-target activity. Nature Chemical Biology 2018. 14: 311–316 6. Mou H*, Smith J*, et al, Moore M#, Weng Z#, Xue W#. CRISPR-mediated genome editing induces exon skipping by alternative splicing or exon deletion. Genome Biology 2017. 18:108 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. 114(14):3648-3653 8. Song C-Q*, Li Y*, Mou H, Moore J, Park A, Pomyen Y, Hough S, Kennedy Z, Fischer A, Yin H, Anderson DG, Conte Jr D, Zender L, Wang XW, Thorgeirsson S, Weng Z#, Xue W#. Genome-wide CRISPR Screen Identifies Regulators of Mitogen-Activated Protein Kinase as Suppressors of Liver Tumors in Mice. Gastroenterology. 2017. 152(5):1161-1173.e1 9. 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 4 DG#. Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components to the mouse liver. Nat Biotechnology 2016. 34: 328-333. 10. Wang D*, Mou H*, Li SY*, 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. Human Gene Therapy 2015. 26:432-42. 11. Li Y*, Park A*, 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.