Junwei Shi, Ph.D.

faculty photo
Assistant Professor of Cancer Biology
Department: Cancer Biology
Graduate Group Affiliations

Contact information
421 Curie Blvd., 610 BRB II/III
Philadelphia, PA 19104-6160
Office: 215-746-5733
Fax: 215-573-6725
Lab: 215-746-3614
Education:
B.S. (Biotechnology)
Sun Yat-sen University (China), 2008.
Ph.D. (Molecular and Cellular Biology)
Stony Brook University, SUNY, 2016.
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Description of Research Expertise

Current Research
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and causes up to 800,000 deaths annually worldwide. My lab focuses on understanding molecular pathways that support HCC growth. A major clinical challenge for HCC is that most patients are diagnosed at advanced stages, and no curative treatments are currently available. The multikinase inhibitor Sorafenib is the only approved therapy for late stage HCC, which confers only an approximately 3-month median survival benefit.

Current areas of interest within the lab include: (1) Defining the functional importance of epigenetic regulators in HCC, (2) Dissecting the signal transduction pathways that are required for HCC maintenance, and (3) Developing new functional genomic tools.

Research Details:
While whole exome sequencing of HCC cancer genome revealed many oncogene mutations, none of these genetic alterations lead to directly actionable therapeutic opportunities. A challenge in the HCC research community is to reveal non-oncogene dependencies that could be exploited with targeted therapeutics. A major objective of the lab is to annotate and dissect these non-oncogene vulnerabilities in HCC. To approach this, we will use our recently developed domain-focused CRISPR genetic knockout screening technology. This method directs the CRISPR-mediated mutagenesis to gene sequences encoding critical protein domains, which generates larger fraction of functional null alleles thus increases the severity in a phenotypic genetic screening. In contrast to RNA interference-based methods or prior CRISPR-based screening approaches, this new method is not only more efficient than other screening approaches, but also has the potential to evaluate protein domain function directly from genetic screening, and may allow high-throughput identification of protein domains that are suitable drug targets in cancer. Coupling with functional genomics screening, biochemical, and pre-clinical mouse models of HCC approaches, we will investigate the aberrant transcription signaling networks of HCC and explore them as potential therapeutic opportunities in HCC. Since genetic screenings are only as successful as the underlying technology, a major focus of the lab is to further optimize and expand our screening toolbox. Projects are underway to engineer different Cas proteins for multiplex genetic screening using a variety of methods, including structure-guided rational design and directed evolution. Our ultimate goal is to uncover complex genetic interactions in HCC that are therapeutically tractable.

Lab Members:

Krista Budinich, Research Specialist
Zhendong Cao, Graduate Researcher
Emily Duffner, Research Specialist
Rodrigo Gier, Research Specialist
Brandon Hayes, Graduate Student
Henry Sanchez, Graduate Student
Sydney Shaffer, Postdoctoral Researcher
Deb Sneddon, Administrative Coordinator
Nancy Yang, Undergraduate Researcher

Selected Publications

Maria Paz Zafra, Emma M Schatoff, Alyna Katti, Miguel Foronda, Marco Breinig, Anabel Y Schweitzer, Amber Simon, Teng Han, Sukanya Goswami, Emma Montgomery, Jordana Thibado, Edward R Kastenhuber, Francisco J Sánchez-Rivera, Junwei Shi, Christopher R Vakoc, Scott W Lowe, Darjus F Tschaharganeh, and Lukas E Dow: Optimized base editors enable efficient editing in cells, organoids and mice. Nature Biotechnology 10.1038/nbt.4194, Jan 2019 Notes: Epub ahead of print, Jul 2018.

Bin Lu, Olaf Klingbeil, Yusuke Tarumoto, Tim D. D. Somerville, Yu-Han Huang, Yiliang Wei, Dorothy C. Wai, Jason K.K. Low, Joseph P. Milazzo, Xiaoli S. Wu, Zhendong Cao, Xiaomei Yan, Osama E. Demerdash, Gang Huang, Joel P. Mackay, Justin B. Kinney, Junwei Shi#, and Christopher R. Vakoc#. # co-corresponding author: A transcription factor addiction in leukemia imposed by the MLL promoter sequence. Cancer Cell 10;34(6): 970-981, Dec 2018.

Gerard L. Brien, David Remillard, Junwei Shi, Matthew L. Hemming, Jonathon Chabon, Kieran Wynne, Eugène T. Dillon, Gerard Cagney, Guido Van Mierlo, Marijke P Baltissen, Michiel Vermeulen, Jun Qi, Stefan Fröhling, Nathanael S. Gray, James E. Bradner, Christopher R. Vakoc and Scott A. Armstrong: Targeted degradation of BRD9 reverses oncogenic gene expression in synovial sarcoma. Elife 15;7. pii: e41305., Nov 2018.

Yu-Han Huang, Xiaoli Wu, Olaf Klingbeil, Xue-Yan He, Gayatri Arun, Bin Lu, Tim D. D. Somerville, Joseph P. Milazzo, John E. Wilkinson, Osama E. Demerdash, David L. Spector, Mikala Egeblad, Junwei Shi, and Christopher R. Vakoc: POU2F3 is a master regulator of a tuft cell-like variant of small cell lung cancer. Genes and Development Page: 32(13-14):915-928, Jul 2018.

Jeremy D Grevet, Xianjiang Lan, Nicole Hamagami, Christopher R Edwards, Laavanya Sankaranarayanan, Xinjun Ji, Saurabh K Bhardwaj, Carolyne J Face, David F Posocco, Osheiza Abdulmalik, Cheryl A Keller, Belinda Giardine, Simone Sidoli, Ben A Garcia, Stella T Chou, Stephen A Liebhaber, Ross C Hardison, Junwei Shi#, and Gerd A Blobel# (# co-corresponding author): Domain-focused CRISPR screen identifies HRI as a fetal hemoglobin regulator in human erythroid cells. Science Page: 361(6399):285-290, Jul 2018.

Alexandra Hörmann, Barbara Hopfgartner, Thomas Köcher, Maja Corcokovic, Teresa Krammer, Christoph Reiser, Gerd Bader, Junwei Shi, Katharina Ehrenhöfer, Simon Wöhrle, Norbert Schweifer, Christopher R Vakoc, Norbert Kraut, Mark Pearson, Mark Petronczki, and Ralph A Neumüller: RIOK1 kinase activity is required for cell survival irrespective of MTAP status. Oncotarget Page: 9(47):28625-28637, Jun 2018.

Yusuke Tarumoto, Bin Lu, Tim D. D. Somerville, Yu-Han Huang, Joseph P. Milazzo, Xiaoli S. Wu, Olaf Klingbeil, Osama E. Demerdash, Junwei Shi#, and Christopher R. Vakoc#. # co-corresponding author : LKB1, Salt-Inducible Kinases, and MEF2C are linked dependencies in acute myeloid leukemia. Molecular Cell. Molecular Cell, 10.1016/j.molcel.2018.02.011: online, Mar 2018.

Vivek Behera, Perry Evans, Carolyne J Face, Nicole Hamagami, Laavanya Sankaranarayanan, Cheryl A Keller, Belinda Giardine, Kai Tan, Ross C Hardison, Junwei Shi, and Gerd A Blobel.: Exploiting genetic variation to uncover rules of transcription factor binding and chromatin accessibility. Nature Communication Page: 9(1):782, Feb 2018.

Isaia Barbieri, Konstantinos Tzelepis, Luca Pandolfini, Junwei Shi, Gonzalo Millán-Zambrano, Samuel C Robson, Demetrios Aspris, Valentina Migliori, Andrew J Bannister, Namshik Han, Etienne De Braekeleer, Hannes Ponstingl, Alan Hendrick, Christopher R Vakoc, George S Vassiliou, and Tony Kouzarides: Promoter-bound METTL3 maintains myeloid leukaemia by m6A-dependent translation control. Nature 552(7683): 126-131, Dec 2017.

Nathan Singh, Junwei Shi, Carl H June, and Marco Ruella.: Genome-Editing Technologies in Adoptive T Cell Immunotherapy for Cancer. Curr Hematol Malig Rep 12(6):522-529, Dec 2017.

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Last updated: 12/12/2018
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