Publications

2023

Li Zhang, Jonathan J Park, Matthew B Dong, Deanna Arsala, Shengqian Xia, Jianhai Chen, Dylan Sosa, Jared E Atlas, Manyuan Long†, Sidi Chen†. Human gene age dating reveals an early and rapid evolutionary construction of the adaptive immune system. Genome Biology and Evolution 2023 doi: https://doi.org/10.1093/gbe/evad081.
Wang G, Zhang F, Chow RD, He E, Zhu L, Han Q, Chen S†. Rational design of immune gene therapy combinations via in vivo CRISPR activation screen of tumor microenvironment modulators. bioRxiv 2023 doi: https://doi.org/10.1101/2023.03.14.532665
Zhang F, Wang G, Chow RD, He E, Majety M, Zhang Y, Chen S†. Multiplexed repression of immunosuppressive genes as combinatorial cancer immunotherapy. bioRxiv 2023. doi: https://doi.org/10.1101/2023.03.14.532668
Renauer PA, Park JJ, Bai M, Acosta A, Lee WH, Lin GH, Zhang Y, Dai X, Wang G, Errami Y, Wu T, Clark P, Ye L, Yang Q, Chen S†. Immunogenetic metabolomics revealed key enzymes that modulate CAR-T metabolism and function. bioRxiv 2023. doi: https://doi.org/10.1101/2023.03.14.532663
Peng L, Renauer PA, Ye L, Yang L, Park JJ, Chow RD, Zhang Y, Lin Q, Bai M, Sanchez A, Zhang Y, Lam SZ, Chen S†. Perturbomics of tumor-infiltrating NK cells bioRxiv 2023. doi: https://doi.org/10.1101/2023.03.14.532653
Ye L, Lam SZ, Yang L, Suzuki K, Zou Y, Lin Q, Zhang Y, Clark P, Peng L, Chen S†. Therapeutic immune cell engineering with an mRNA : AAV-Sleeping Beauty composite system bioRxiv 2023 doi: https://doi.org/10.1101/2023.03.14.532651
Zhou X*, Cao H*, Fang SY, Chow RD, Tang K, Mejety M, Bai M, Dong MB, Renauer PA, Shang X, Suzuki K, Levchenko A, Chen S†. CTLA-4 tail fusion enhances CAR-T anti-tumor immunity. bioRxiv 2023 doi: https://doi.org/10.1101/2023.03.14.532655
Ren P*, Hu Y*, Peng L*, Yang L, Suzuki K, Fang Z, Bai M, Zhou L, Feng Y, Zou Y, Xiong Y†, Chen S†. Function and Cryo-EM structures of broadly potent bispecific antibodies against multiple SARS-CoV-2 Omicron sublineages. bioRxiv 2022 PMID: 35982661. doi: https://doi.org/10.1101/2022.08.09.503414
Dong MB, Tang K, Zhou X, Shen J, Chen K, Kim HR, Zhou J, Cao H, Vandenbulcke E, Zhang Y, Chow RD, Du A, Suzuki K, Fang SY, Majety M, Dai X, Chen S†. Cas12a/Cpf1 knock-in mice enable efficient multiplexed immune cell engineering bioRxiv2023 doi: https://doi.org/10.1101/2023.03.14.532657
Zhenhao Fang*, Valter S. Monteiro*, Paul A. Renauer, Xingbo Shang, Kazushi Suzuki, Xinyu Ling, Meizhu Bai, Yan Xiang, Andre Levchenko, Carmen J. Booth, Carolina Lucas† & Sidi Chen†. Cell Research 2023. https://www.nature.com/articles/s41422-023-00792-5. PDF
Dai X*,Park JJ*, Du Y*, Na Z*, Lam SZ*, … Chen S†. Massively parallel knock-in engineering of human T cells. Nature Biotechnology 2023. https://www.nature.com/articles/s41587-022-01639-x PDF

Yale News about our new Nature Biotechnology paper: https://www.yalecancercenter.org/news-article/yale-scientists-enable-massively-parallel-dna-insertions-into-human-cells/

Nature Biotechnology research briefing about our new paper: https://www.nature.com/articles/s41587-023-01664-4
Park JJ*, Lee KV*, … Chen S. Machine learning identifies T cell receptor repertoire signatures associated with COVID-19 severity. Communications Biology 2023. https://www.nature.com/articles/s42003-023-04447-4 PDF
Ren P*, Peng L*, … Chen S. RAMIHM generates fully human monoclonal antibodies by rapid mRNA immunization of humanized mice and BCR-seq. Cell Chemical Biology 2023. Cover Article. https://www.sciencedirect.com/science/article/pii/S245194562200455X?dgcid=coauthor PDF

2022

Park J.J.*, Codina A*, Ye, L.*, … Chen S. Double knockout CRISPR screen for cancer resistance to T cell cytotoxicity. Journal of Hematology & Oncology 2022. https://jhoonline.biomedcentral.com/articles/10.1186/s13045-022-01389-y PDF
Song J.*, Chow R.D.*, Pena-Hernandez, M.*, Zhang L.*, … Chen S., Wilen C.B.**, Lee S.** LRRC15 inhibits SARS-CoV-2 cellular entry in trans. Plos Biology 2022. https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3001805 PDF
Fang Z., Monteiro V.S., Hahn A.M., Grubaugh N.D., Lucas C., Chen S. Bivalent mRNA vaccine booster induces robust antibody immunity against Omicron lineages BA.2, BA.2.12.1, BA.2.75 and BA.5. Cell Discovery 2022. https://www.nature.com/articles/s41421-022-00473-4 PDF
Park JJ., Lee K.A.V., Lam S.Z., Tang K., Chen S. Genome Engineering for Next-Generation Cellular Immunotherapies. Biochemistry 2022. https://pubs.acs.org/doi/full/10.1021/acs.biochem.2c00340 PDF
Na Z.*, Dai X.*, Zheng S., Bryant C.J., Loh K.H., Su X., … & Chen S. & Slavoff S.A.. Mapping subcellular localizations of unannotated microproteins and alternative proteins with MicroID. Mol. Cell 2022. https://doi.org/10.1016/j.molcel.2022.06.035. PDF
Peng, L.*, Fang, Z.*, Renauer, P.A.*, McNamara, A., Park, J.J., Lin, Q., … Wilen, C. B. & Chen, S. Multiplexed LNP-mRNA vaccination against pathogenic coronavirus species. Cell Reports 2022. https://www.cell.com/cell-reports/fulltext/S2211-1247(22)00969-X. PDF
Fang, Z.*, Peng, L.*, Filler, R., Suzuki, K., McNamara, A., Lin, Q., … Wilen, C. B.** & Chen, S.** Omicron-specific mRNA vaccination alone and as a heterologous booster against SARS-CoV-2. Nature Communications 2022. doi: https://doi.org/10.1038/s41467-022-30878-4. PDF
Fang, Z.*, Peng, L.*, Lucas C., Lin, Q., Zhou, L., Yang, L., Feng, Y., … Wilen, C. B. & Chen, S. (2022). Heterotypic vaccination responses against SARS-CoV-2 Omicron BA. 2. Cell Discovery 2022. https://doi.org/10.1038/s41421-022-00435-w PDF
Peng, L.*, Renauer, P. A.*, Ökten, A.*, Fang, Z.*, Park, J. J.*, Zhou, X.*, … Wilen, C. B.** & Chen, S**. Variant-specific vaccination induces systems immune responses and potent in vivo protection against SARS-CoV-2. Cell Reports Medicine 2022, 100634. 10.1016/j.xcrm.2022.100634 PDF
Peng, L.*, Hu, Y.*, Mankowski, M. C.*, Ren, P.*, Chen, R. E., Wei, J., … Wilen, C. B.**, Xiong, Y.** & Chen, S**. (2022). Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B. 1.617. Nature Communications 2022. https://www.nature.com/articles/s41467-022-29288-3 PDF
Ye, L.*, Park, J. J.*, Peng, L.*, Yang, Q.*, Chow, R. D., Dong, M. B., … & Chen, S. A genome-scale gain-of-function CRISPR screen in CD8 T cells identifies proline metabolism as a means to enhance CAR-T therapy. Cell Metabolism 2022. 10.1016/j.cmet.2022.02.009 PDF
Bock, C., Datlinger, P., Chardon, F., Coelho, M. A., Dong, M. B., Lawson, K. A., … & Zhuang, X. High-content CRISPR screening. Nature Reviews Methods Primers 2022. https://www.nature.com/articles/s43586-021-00093-4 PDF
Fang Z*, Peng L*, Filler R, Suzuki K, McNamara A, Lin Q, Renauer PA, Yang L, Menasche B, Sanchez A, Ren P, Xiong Q, Strine M, Clark P, Lin C, Ko AI, Grubaugh ND, Wilen CB, Chen S. Omicron-specific mRNA vaccination alone and as a heterologous booster against SARS-CoV-2. bioRxiv 2022. doi: https://doi.org/10.1101/2022.02.14.480449 PDF
Park JJ, Codina A, Ye L, Lam S, Guo J, Clark P, Zhou X, Peng L, Chen S. Double knockout CRISPR screen in cancer resistance to T cell cytotoxicity. bioRxiv 2022. doi: https://doi.org/10.1101/2022.03.01.482556 PDF

2021

Chow RD, Majety M, Chen S. The aging transcriptome and cellular landscape of the human lung in relation to SARS-CoV-2. Nature Communications 2021. doi:10.1038/s41467-020-20323-9. https://rdcu.be/cc1O0. PDF
Park JJ, Chen S. Metaviromic identification of discriminative genomic features in SARS-CoV-2 using machine learning. Cell Patterns 2021. doi:10.1016/j.patter.2021.100407. PDF
Park JJ, Lee K, Lam S, Chen S. T cell receptor repertoire signatures associated with COVID-19 severity. bioRxiv (preprint) 2021. doi: https: 10.1101/2021.11.30.470640. PDF
Peng, L., Park, J.J., Fang, Z., Zhou, X., Dong, M.B., Xiong, Q., Lin, C. and Chen, S. Systems immune profiling of variant-specific vaccination against SARS-CoV-2. bioRxiv 2021. doi:10.1101/2021.12.02.471028. PDF
Peng L, Hu Y, Mankowski M, Ren P, Chen R, Wei J, Zhao M, Li T, Tripler T, Ye L, Chow R, Fang Z, Wu C, Dong MB, Cook M, Wang G, Clark P, Nelson B, Klein D, Sutton R, Diamond MS, Wilen CB, Xiong Y, Chen S. Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B. 1.617. bioRxiv 2021. doi:10.1101/2021.12.21.473733. PDF
Dong MB, Tang K, Zhou X, Zhou JJ, Chen S. Tumor immunology CRISPR screening: present, past, and future. Trends in Cancer 2021. doi: 10.1016/j.trecan.2021.11.009. PDF

2020

Yuan S*, Peng L*, Park JJ, Hu Y, Devarkar SC, Dong MB, Shen Q, Wu S, Chen S**, Lomakin I**, Xiong Y**. Nonstructural protein 1 of SARS-CoV-2 is a potent pathogenicity factor redirecting host protein synthesis machinery toward viral RNA. Molecular Cell 2020. doi: 10.1016/j.molcel.2020.10.034. PDF
Chow RD*, Chen JS*, Shen J, and Chen S. A web tool for the design of prime-editing guide RNAs. Nature Biomedical Engineering 2020. doi: 10.1038/s41551-020-00622-8. PDF
Wang G*, Chow RD*, Zhu L*, Bai Z*, Ye L, Zhang F, Renauer PA, Dong MB, Dai X, Zhang X, Du Y, Cheng Y, Niu L, Chu Z, Kim K, Liao C, Clark P, Errami Y, Chen S. CRISPR-GEMM pooled mutagenic screening identifies KMT2D as a major modulator of immune checkpoint blockade. Cancer Discovery 2020. doi: 10.1158/2159-8290.CD-19-1448. PDF

2019

Wang G*, Chow RD*, Bai Z, Zhu L, Errami Y, Dai X, Dong MB, Ye L, Zhang X, Renauer PA, Park JJ, Shen L, Ye H, Fuchs CS, Chen S. Multiplexed activation of endogenous genes by CRISPRa elicits potent antitumor immunity. Nature Immunology 2019. doi: 10.1038/s41590-019-0500-4. PDF
Ye L*, Park JJ*, Dong MB*, Yang Q, Chow RD, Peng L, Du Y, Guo J, Dai X, Wang G, Errami Y, Chen S. In vivo CRISPR screening in CD8 T cells with AAV-Sleeping Beauty hybrid vectors identifies membrane targets for improving immunotherapy for glioblastoma. Nature Biotechnology 2019. doi: 10.1038/s41587-019-0246-4. PDF
Dong MB*, Wang G*, Chow RD*, Ye L*, Zhu L, Dai X, Park JJ, Kim HR, Errami Y, Guzman CD, Zhou X, Chen KY, Renauer PA, Du Y, Shen J, Lam SZ, Zhou JJ, Lannin DR, Herbst RS, Chen S. Systematic Immunotherapy Target Discovery Using Genome-Scale In vivo CRISPR Screens in CD8 T Cells. Cell 2019. doi: 10.1016/j.cell.2019.07.044. PDF.
in vitro screen raw count table
in vivo screen raw count table
Chow RD*, Wang G*, Ye L*, Codina A, Kim HR, Shen L, Dong MB, Errami Y, Chen S. In vivo profiling of metastatic double knockouts through CRISPR-Cpf1 screens. Nature Methods 2019. doi: 10.1038/s41592-019-0371-5. PDF
Dai X*, Park JJ*, Du Y, Kim HR, Wang G, Errami Y, Chen S. One-step generation of modular CAR-T with AAV-Cpf1. Nature Methods 2019. doi: 10.1038/s41592-019-0329. PDF
Codina A*, Renauer PA*, Wang G*, Chow RD*, Park JJ**, Ye H**, Zhang K**, Dong M**, Gassaway B, Ye L, Errami Y, Shen L, Chang A, Jain D, Herbst RS, Bosenberg M, Rinehart J, Fan R, Chen S. Convergent identification and interrogation of tumor-intrinsic factors that modulate cancer immunity in vivo. Cell Systems 2019. 10.1016/j.cels.2019.01.004. PDF

2018

Chow RD, Chen S. Sno-derived RNAs are prevalent molecular markers of cancer immunity. Oncogene. 2018 Aug 2. PDF
Ye L, Wang C, Hong L, Sun N, Chen D, Chen S*, Han F*. Programmable DNA repair with CRISPRa/i enhanced homology-directed repair efficiency with a single Cas9. Cell Discovery. 2018 Jul 24;4:46. PDF
Chow RD, Kim HR, Chen S. Programmable sequential mutagenesis by inducible Cpf1 crRNA array inversion. Nature Communications. 2018 May 15;9(1):1903. PDF
Chow RD, Chen S. Cancer CRISPR screens in vivo. Trends in Cancer. 2018 Mar 29. PDF
Wang G*, Chow RD*, Ye L, Guzman CD, Dai X, Dong MB, Zhang F, Sharp PA, Platt RJ, Chen S. Mapping a functional cancer genome atlas of tumor suppressors in mouse liver using AAV-CRISPR mediated direct in vivo screening. Science Advances. 2018 Feb 28;4(2). PDF

2017

Chow RD*, Guzman CD*, Wang G*, Schmidt F*, Youngblood MW, Ye L, Errami Y, Dong MB, Martinez MA, Zhang S, Renauer P, Bilguvar K, Gunel M, Sharp PA, Zhang F, Platt RJ, Chen S. AAV-mediated direct in vivo CRISPR screen identifies functional suppressors in glioblastoma. Nature Neuroscience. 2017 Aug 14. PDF

2015

Chen S*, Sanjana NE*, Zheng K, Shalem O, Lee K, Shi X, Scott DA, Song J, Pan JQ, Weissleder R, Lee H, Zhang F, Sharp PA. Genome-wide CRISPR screen in a mouse model of tumor growth and metastasis. Cell. 2015 Mar 12;160(6):1246-60. PDF

2014

Platt RJ*, Chen S*, Zhou Y, Yim MJ, Swiech L, Kempton HR, Dahlman JE, Parnas O, Eisenhaure TM, Jovanovic M, Graham DB, Jhunjhunwala S, Heidenreich M, Xavier RJ, Langer R, Anderson DG, Hacohen N, Regev A, Feng G, Sharp PA, Zhang F. CRISPR-Cas9 knockin mice for genome editing and cancer modeling. Cell. 2014 Oct 9;159(2):440-55. PDF
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. PDF
Chen S*, Xue Y*, Wu X, Le C, Bhutkar A, Bell EL, Zhang F, Langer R, Sharp PA. Global microRNA depletion suppresses tumor angiogenesis. Genes Dev. 2014 May 15;28(10):1054-67. PDF

2013

Chen S, Krinsky BH, Long M. New genes as drivers of phenotypic evolution. Nat Rev Genet. 2013 Sep;14(9):645-60. PDF

2012

Chen S*, Ni X*, Krinsky BH, Zhang YE, Vibranovski MD, White KP, Long M. Reshaping of global gene expression networks and sex-biased gene expression by integration of a young gene. EMBO J. 2012 Jun 13;31(12):2798-809. PDF
Chen S, Spletter M, Ni X, White KP, Luo L, Long M. Frequent recent origination of brain genes shaped the evolution of foraging behavior in Drosophila. Cell Rep. 2012 Feb 23;1(2):118-32. PDF

2010

Chen S, Zhang YE, Long M. New genes in Drosophila quickly become essential. Science. 2010 Dec 17;330(6011):1682-5. PDF