CDI Publications
2022
Synthetic cytokine circuits that drive T cells into immune-excluded tumors
Allen GM*, Frankel NW*, Reddy NR, Bhargava HK, Yoshida MA, Stark SR, Purl M, Lee J, Yee J, Yu W, Li AW, Garcia KC, El-Samad H, Roybal KT, Spitzer MH, Lim WA
Science. doi: https://doi.org/10.1126/science.aba1624.
Explanatory Video: https://www.youtube.com/watch?v=cDGgPpfrcgk.
Programming Multicellular Assembly with Synthetic Cell Adhesion Molecules
Stevens AJ, Harris AR, Gerdts J, Kim KH, Trentesaux C, Ramirez JT, McKeithan WL, Fattahi F, Klein OD, Fletcher DA, Lim WA
Nature. doi: https://doi.org/10.1038/s41586-022-05622-z.
Explanatory Video: https://www.youtube.com/watch?v=U3zRAWkeEtE.
Decoding CAR T cell phenotype using combinatorial signaling motif libraries and machine learning
Daniels KG, Wang S, Simic MS, Bhargava HK, Capponi S, Tonai Y, Yu W, Bianco S, Lim WA
Science. doi: https://doi.org/10.1126/science.abq0225. full text: https://www.science.org/stoken/author-tokens/ST-899/full.
Explanatory Video: https://www.youtube.com/watch?v=iQT-4yN0ziw.
The emerging era of cell engineering: Harnessing the modularity of cells to program complex biological function.
Lim WA
Science. doi: https://doi.org/10.1126/science.add9665. full text: https://www.science.org/stoken/author-tokens/ST-872/full.
Rethinking cancer targeting strategies in the era of smart cell therapeutics.
Allen GM, Lim WA
Nature Reviews Cancer. doi: https://doi.org/10.1038/s41568-022-00505-x.
Pooled screening of CAR T cells identifies diverse immune signaling domains for next-generation immunotherapies.
Goodman DB, Azimi CS, Kearns K, Talbot A, Garakani K, Garcia J, Patel N, Hwang B, Lee D, Park E, Vykunta VS, Shy BR, Ye CJ, Eyquem J, Marson A, Bluestone JA, Roybal KT.
Science Translational Medicine. doi: https://doi.org/10.1126/scitranslmed.abm1463.
Modular design of synthetic receptors for programmed gene regulation in cell therapies.
Zhu I, Liu R, Garcia JM, Hyrenius-Wittsten A, Piraner DI, Alavi J, Israni DV, Liu B, Khalil AS, Roybal KT.
Cell. doi: https://doi.org/10.1016/j.cell.2022.03.023.
CoRa-A general approach for quantifying biological feedback control.
Gómez-Schiavon M, El-Samad H.
Proc Natl Acad Sci USA. doi: https://doi.org/10.1073/pnas.2206825119.
2021
SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma.
Joseph H. Choe, Payal B. Watchmaker, Milos S. Simic, Ryan D. Gilbert, Aileen W. Li, Nira A. Krasnow, Kira M. Downey, Wei Yu, Diego A. Carrera, Anna Celli, Juhyun Cho, Jessica D. Briones, Jason M. Duecker, Yitzhar e. Goretsky, Ruth Dannenfelser, Lia Cardarelli, Olga Troyanskaya, Sachdev S. Sidhu, Kole T. Roybal, Hideho Okada, Wendell A. Lim.
Science Translational Medicine. doi: https://doi.org/10.1126/scitranslmed.abe7378.
Video: Smart Cell Therapies for Solid Cancers
Video: Smart Immune Cells for Glioblastoma
SynNotch CAR circuits enhance solid tumor recognition and promote persistent antitumor activity in mouse models.
Axel Hyrenius-Wittsten, Yang Su, Minhee Park, Julie M. Garcia, Josef Alavi, Nathaniel Perry, Garrett Montgomery, Bin Liu, Kole T. Roybal.
Science Translational Medicine. doi: https://doi.org/10.1126/scitranslmed.abd8836.
T cell circuits that sense antigen density with an ultrasensitive threshold.
Rogelio A. Hernandez-Lopez, Wei Yu, Katie Cabral, Olivia Creasey, Maria del Pilar Lopez Pazmino, Yurie Tonai, Arsenia De Guzman, Anna Mäkelä, Kalle Saksela, Zev J. Gartner, Wendell A. Lim.
Science. doi: https://doi.org/10.1101/2021.01.21.427654.
T cells selectively filter oscillatory signals on the minutes timescale.
Geoff P. O’Donoghue, Lukasz J. Bugaj, Warren Anderson, Kyle G. Daniels, David J. Rawlings, Wendell A. Lim.
Proceedings of the National Academy of Sciences. doi: https://doi.org/10.1073/pnas.2019285118.
CoRa – A general approach for quantifying biological feedback control
Gómez-Schiavon, M., El-Samad, H.
BioRxiv, under review; doi: https://doi.org/10.1101/2020.10.09.334078
TuNR: Orthogonal Control of Mean and Variability of Endogenous Genes in a Human Cell Line.
Bonny R., Fonseca J.P., Park J.E., El-Samad, H.
Nature Communications, doi: 2020.05.23.112979.
2020
Precise T cell recognition programs designed by transcriptionally linking multiple receptors.
Williams JZ*, Allen GM*, Shah DH, Sterin IS, Kim KH, Garcia VP, Shavey GE, Yu W, Puig-Saus C, Tsoi J, Ribas A, Roybal KT, Lim WA.
Science. doi: 10.1126/science.abc6270
DNA scaffolds enable efficient and tunable functionalization of biomaterials for immune cell modulation.
Huang, X., Williams, J.Z., Chang, R, Li, Z., Burnett, C.E., Hernandez-Lopez, R., Setiady, I., Gai, E., Patterson, D.M., Yu, W., Roybal, K.T., Lim, W.A., Desai, T.A.
Nature Nanotechnology.
Engineering cytokines and cytokine circuits: Learning to speak the secret language of immune cells could improve immunotherapies.
Li, A.W., Lim, W.A,
Science.
Engineering synthetic morphogen systems that can program multicellular patterning.
Toda S, McKeithan WL, Hakkinen TJ, Lopez P, Klein OD, Lim WA.
Science. doi: https://doi.org/10.1126/science.abc0033
De novo design of protein logic gates.
Chen, Z., Kibler, R.D., Hunt, A., Busch, F., Pearl, J., Jia, M., VanAernum, Z.L., Wicky, B.I.M., Dods, G., Liao, H., Wilken, M.S., Ciarlo, C., Green, S., El-Samad, H., Stamatoyannopoulos, J., Wysocki, V.H., Jewett, M.C., Boyken, S.E., Baker, D.
Science. doi: https://doi.org/10.1126/science.aay2790
Discriminatory Power of Combinatorial Antigen Recognition in Cancer T Cell Therapies
Dannenfelser R, Allen GM, VanderSluis B, Koegel AK, Levinson S, Stark SR, Yao V, Tadych A, Troyanskaya OG, Lim WA. ,
Cell Systems.
Engineering T Cells to Treat Cancer: The Convergence of Immuno-Oncology and Synthetic Biology
Choe H, Williams JZ, and Lim WA.
Annual Review of Cancer Biology. doi: https://doi.org/10.1146/annurev-cancerbio-030419-033657
Multidimensional characterization of parts enhances modeling accuracy in genetic circuits.
Dods G, Gómez-Schiavon M., Ng. A.H., El-Samad H.
ACS Synthetic Biology; doi: https://doi.org/10.1101/2020.05.30.122077
De novo design of protein logic gates.
Chen Z., Kibler R.D., Hunt A., Busch F., Pearl J., Jia M., VanAernum Z.L., Wicky B., Dods G., Liao H., El-Samad H., Jewett M.C., Boyken S.E., Baker D.
Science; doi: 10.1126/science.aay2790
Optogenetic control reveals differential promoter interpretation of transcription factor nuclear translocation dynamics.
Chen S.Y., Osimiri L.C., Chevalier M.W., Bugaj L.J., Ng A.H., Stewart-Ornstein J., Neves L.T., El-Samad H.
Cell Systems; DOI: 10.1101/548255.
Assembly of Genetic Circuits with the Mammalian ToolKit.
Fonseca, J., Bonny, A., Town, J. & El-Samad, H.
BIO-PROTOCOL.
2019
De novo design of bioactive protein switches. Langan, R.A., Boyken, S.E., Ng, A.H., Samson, J.A., , Dods, G., Westbrook, A., Nguyen, T.H., Lajoie, M.J., Chen, Z., Berger, S., Khipple Mulligan, V., Dueber, J.E., Novak, W.R.P., El-Samad, H., Baker, D. Nature. 2019; doi:https://doi.org/10.1038/s41586-019-1432-8
Modular and tunable biological feedback control using a de novo protein switch. Ng, A.H., Nguyen, T.H., Gómez-Schiavon, M., Dods, G., Langan, R.A., Boyken, S.E., Samson, J.A., Waldburger, L.M., Dueber, J.E., Baker, D., El-Samad, H. Nature. 2019; doi:https://doi.org/10.1038/s41586-019-1425-7
Control Theoretical Concepts for Synthetic and Systems Biology. Baetica, A.A., Westbrook, A.,El-Samad, H. Curr Opin Syst Biol. 2019; doi:https://doi.org/10.1016/j.coisb.2019.02.010
Engineering cell–cell communication networks: programming multicellular behaviors. Toda, S., Frankel, N.W., Lim, W.A, Current Opinion in Chemical Biology. 2019
The Design Principles of Biochemical Timers: Circuits that Discriminate between Transient and Sustained Stimulation. Gerardin, J., Reddy, N. R., Lim WA*. Cell Systems. 2019
A Toolkit for Rapid Modular Construction of Biological Circuits in Mammalian Cells. Fonseca JP, Bonny AR, Kumar GR, Ng AH, Town J, Wu QC, Aslankoohi E, Chen SY, Dods G, Harrigan P, Osimiri LC, Kistler AL, El-Samad H ACS Synth Biol. 2019 Nov 15;8(11):2593-2606. doi: 10.1021/acssynbio.9b00322. Epub 2019 Nov 5.
Controlling CRISPR-Cas9 with ligand-activated and ligand-deactivated sgRNAs. Kundert K., Lucas J.E., Watters K.E., Fellmann C., Ng A.H., Heineike B.M., Fitzsimmons C.M., Oakes C.K., Qu J., Prasad N., Rosenberg O.S., Savage D.F., El-Samad H., Doudna J.A., Kortemme T. Nat Commun; DOI: 10.1038/s41467-019-09985-2.
Design and analysis of a Proportional-Integral-Derivative controller with biological molecules. Chevalier M., Schiavon-Gomez M., Ng A.H., and El-Samad H. Cell Systems; DOI: 10.1101/248419
2018
Programming self-organizing multicellular structures with synthetic cell-cell signaling. Toda S, Blauch LR, Tang SKY, Morsut L, Lim WA. Science. 2018 Jul 13;361(6398):156-162. doi: 10.1126/science.aat0271.
Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities. Roybal KT, Lim WA. Annu Rev Immunol. 2017 Apr 26;35:229-253. doi: 10.1146/annurev-immunol-051116-052302. Review.
2017
The Principles of Engineering Immune Cells to Treat Cancer. Wendell A. Lim and Carl H. June. Cell. 2017 February 9
Engineering Therapeutic T cells: From Synthetic Biology to Clinical Trials. Jonathan H. Esensten, Jeffrey A. Bluestone, Wendell A. Lim. Annu Rev Pathol. 2017 Jan
2016
Engineering T cells with Customized Therapeutic Response Programs Using Synthetic Notch Receptors. KT Roybal, JZ Williams, L Morsut, LJ Rupp, I.Kolinko, JH Choe, WJ Walker, KA McNally, WA Lim. Cell. 2016 October 6
Precision tumor recognition by T cells with combinatorial antigen-sensing circuits. Kole T. Roybal, Levi J. Rupp, Leonardo Morsut, Whitney J. Walker, Krista A. McNally, Jason S. Park, Wendell A. Lim. Cell. 2016 Feb. 11
Engineering customized cell sensing and response behaviors using synthetic notch receptors. Leonardo Morsut*, Kole T. Roybal*, Xin Xiong, Russell M. Gordley, Scott M. Coyle, Matthew Thomson, Wendell A. Lim. Cell. 2016 Feb. 11
Robust Synthetic Circuits for Two-Dimensional Control of Gene Expression in Yeast. Aranda-Diaz A., Mace K., Zuleta I., Harrigan P., El-Samad H. ACS Synthetic Biology; DOI:1021/acssynbio.6b00251.