Wendell Lim

Wendell Lim is an American biochemist who is the

Byer's Distinguished Professor of Cellular and Wendell Lim
Molecular Pharmacology at the University of Nationality American
California, San Francisco.[2] He is the director of the Alma mater Harvard University,
UCSF Cell Design Institute.[3] He earned his A.B. in Massachusetts Institute of
chemistry from Harvard University working with Technology
Jeremy Knowles on enzyme evolutionary optimization. Scientific career
He obtained his Ph.D. in biochemistry and biophysics
Fields Bioengineering
from Massachusetts Institute of Technology under the
guidance of Bob Sauer using genetic and biophysical Institutions University of California, San
approaches to understand the role of hydrophobic core Francisco

interactions in protein folding.[4] He then did his Academic Fred Richards[1]

postdoctoral work with Frederic Richards at Yale advisors
University on the structure of protein interaction
domains.[5][6] Lim's work has focused on cell signaling, synthetic biology, and cell engineering,
particularly in immune cells.[7]

Research career

Modular Signaling Proteins

Lim's research has focused on mechanisms of cell signaling – how cells sense their environment and
process this information to make complex functional decisions.[6] He began his career studying the
structure and function of modular signaling domains and scaffold proteins, but became increasingly
interested in the general question of how modularity plays a role in the evolution of new signaling circuits
and networks.[6]

Synthetic and Systems Biology

Lim has been a pioneer in the fields of synthetic and systems biology, asking how rewiring cellular
regulatory circuits can be used to understand fundamental design principles of biological systems. He
showed that signaling proteins and pathways could be functionally rewired in living cells using altered
protein interaction domains, scaffold proteins, and modular allosteric interactions.[8][9][10][11] He helped
pioneer the use of optogenetic response modules as a way to exert control of intracellular signaling and
its use in profiling how cells respond to temporal patterns of stimulation.[12][13][14] He has also worked
on identifying common regulatory network modules that perform fundamental cellular functions such as
amplification, adaptation, spatial self-organization, polarized cell movement, and temporal
sensing.[15][16][17][18] He has been applying these approaches to engineer and understand immune cell
function as well as multicellular self-organization (synthetic development).[18][19]

Engineering therapeutic immune cells

Lim has been a leader in the application of synthetic biology approaches to immune cell engineering and
cell therapy development, advocating approaches for predictively engineering cells with precision
therapeutic functions to treat cancer and other complex diseases.[20][21] His group was the first to develop
small molecule gated chimeric antigen receptors (CARs) [22] as well as the highly flexible synthetic
Notch (synNotch) receptor platform for programming novel transcriptional control circuits.[23][24][25] His
group has shown how these components can be used to design T cell circuits that achieve precision
combinatorial antigen detection and killing of cancer (synNotch to CAR circuits).[24][26][27] His group
has also engineered T cells to recognize specific target tissues, and to deliver genetically encoded
therapeutic payloads to these sites.[25] In addition, Lim's group has used these synthetic receptors to
design positive feedback circuits for sensing antigen density with non-linear thresholds.[28]

Lim was part of the team that invented the CRISPRi system that used modular DNA targeting of inactive
Cas9 to control the transcription of specific endogenous genes.[29] He has also been engineering
multicellular networks that drive specific formation of complex self-organizing tissue-like structures.[18]
Lim and colleagues have advocated applying cell engineering approaches to many other complex
diseases besides cancer, as well as using engineered cells as research tools for probing and perturbing cell
and tissue regulatory networks.[28]

Biotech industry
Lim's work in immune cell engineering led to the founding of the early cell therapy engineering company
Cell Design Labs in 2015, which was acquired by Gilead Sciences in 2017.[30]

Science education and outreach

Lim co-authored the textbook Cell Signaling with colleagues Bruce Mayer and Tony Pawson.[31] His
group has also participated in the synthetic biology outreach program iGEM with San Francisco Bay Area
high school students and teachers.[32][33] He has also conducted creative projects on design thinking,[34]
as well as science and cooking.[35]

Personal life
Lim is Chinese-American and grew up in Chicago, where he graduated from the University of Chicago
Laboratory Schools.[36] He currently lives in San Francisco with his wife and children. Lim is an avid
basketball player, surfer, and artist.[6]

Awards and service

Vienna Center for Molecular Medicine, Landsteiner Lecture (2021)[37]
University of Oregon, Streisinger Lecture (2020)[38]
German Biochemical Society, Feodor Lynden Award (2019)[39]
NIH Transformative R01 ('Re-Designing the T cell') (2014)[40]
Wired Magazine, 50 people who will change the world (2012)[41]
Howard Hughes Medical Institute Investigator (2008–2020)[42]
Protein Society Hans Neurath Award (2010)[43]
Westinghouse Science Talent Search Finalist (1982)[44]
Editorial Board, Science Magazine[45]
Editorial Board, Cell[46]
Burroughs Wellcome Fund, Board of Directors[47]

References
1. "Fred Richards on Academic Tree" (http://academictree.org/chemistry/peopleinfo.php?pid=5
3842).
2. "UCSF Profiles" (https://profiles.ucsf.edu/wendell.lim).
3. "UCSF Cell Design Institute" (https://www.celldesigninstitute.org/). UCSF Cell Design
Institute. Retrieved 2022-07-28.
4. "Wendell Lim" (http://mit.edu/sauerlab/publalumnithree.html#WLim). Retrieved 1 November
2012.
5. "Wendell A. Lim, Ph.D." (http://www.hhmi.org/news/lim_bio.html) HHMI. Retrieved
1 November 2012.
6. Sedwick, C. (17 September 2012). "Wendell Lim: Exploring the path not chosen" (https://ww
w.ncbi.nlm.nih.gov/pmc/articles/PMC3444780). The Journal of Cell Biology. 198 (6): 956–
957. doi:10.1083/jcb.1986pi (https://doi.org/10.1083%2Fjcb.1986pi). PMC 3444780 (https://
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m.nih.gov/22986491).
7. "Research | Lim Lab" (https://limlab.ucsf.edu/research.html). limlab.ucsf.edu. Retrieved
2022-07-29.
8. Park, Sang-Hyun; Zarrinpar, Ali; Lim, Wendell A. (2003-02-14). "Rewiring MAP kinase
pathways using alternative scaffold assembly mechanisms" (https://pubmed.ncbi.nlm.nih.go
v/12511654/). Science. 299 (5609): 1061–1064. Bibcode:2003Sci...299.1061P (https://ui.ad
sabs.harvard.edu/abs/2003Sci...299.1061P). doi:10.1126/science.1076979 (https://doi.org/1
0.1126%2Fscience.1076979). ISSN 1095-9203 (https://search.worldcat.org/issn/1095-920
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pi.semanticscholar.org/CorpusID:1643040).
 9. Dueber, John E.; Mirsky, Ethan A.; Lim, Wendell A. (June 2007). "Engineering synthetic
signaling proteins with ultrasensitive input/output control" (https://pubmed.ncbi.nlm.nih.gov/1
7515908/). Nature Biotechnology. 25 (6): 660–662. doi:10.1038/nbt1308 (https://doi.org/10.1
038%2Fnbt1308). ISSN 1087-0156 (https://search.worldcat.org/issn/1087-0156).
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semanticscholar.org/CorpusID:10465894).
10. Yeh, Brian J.; Rutigliano, Robert J.; Deb, Anrica; Bar-Sagi, Dafna; Lim, Wendell A. (2007-05-
31). "Rewiring cellular morphology pathways with synthetic guanine nucleotide exchange
factors" (https://pubmed.ncbi.nlm.nih.gov/17515921/). Nature. 447 (7144): 596–600.
Bibcode:2007Natur.447..596Y (https://ui.adsabs.harvard.edu/abs/2007Natur.447..596Y).
doi:10.1038/nature05851 (https://doi.org/10.1038%2Fnature05851). ISSN 1476-4687 (http
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17515921). S2CID 4393136 (https://api.semanticscholar.org/CorpusID:4393136).
11. Bashor, Caleb J.; Helman, Noah C.; Yan, Shude; Lim, Wendell A. (2008-03-14). "Using
engineered scaffold interactions to reshape MAP kinase pathway signaling dynamics" (http
s://pubmed.ncbi.nlm.nih.gov/18339942/). Science. 319 (5869): 1539–1543.
Bibcode:2008Sci...319.1539B (https://ui.adsabs.harvard.edu/abs/2008Sci...319.1539B).
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m.nih.gov/18339942). S2CID 365578 (https://api.semanticscholar.org/CorpusID:365578).
12. Levskaya, Anselm; Weiner, Orion D.; Lim, Wendell A.; Voigt, Christopher A. (2009-10-15).
"Spatiotemporal control of cell signalling using a light-switchable protein interaction" (https://
www.ncbi.nlm.nih.gov/pmc/articles/PMC2989900). Nature. 461 (7266): 997–1001.
Bibcode:2009Natur.461..997L (https://ui.adsabs.harvard.edu/abs/2009Natur.461..997L).
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rticles/PMC2989900). PMID 19749742 (https://pubmed.ncbi.nlm.nih.gov/19749742).
13. Toettcher, Jared E.; Weiner, Orion D.; Lim, Wendell A. (2013-12-05). "Using optogenetics to
interrogate the dynamic control of signal transmission by the Ras/Erk module" (https://www.
ncbi.nlm.nih.gov/pmc/articles/PMC3925772). Cell. 155 (6): 1422–1434.
doi:10.1016/j.cell.2013.11.004 (https://doi.org/10.1016%2Fj.cell.2013.11.004). ISSN 1097-
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gov/pmc/articles/PMC3925772). PMID 24315106 (https://pubmed.ncbi.nlm.nih.gov/2431510
6).
14. Bugaj, Lukasz J.; O'Donoghue, Geoff P.; Lim, Wendell A. (2017-01-02). "Interrogating
cellular perception and decision making with optogenetic tools" (https://www.ncbi.nlm.nih.go
v/pmc/articles/PMC5223619). The Journal of Cell Biology. 216 (1): 25–28.
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c/articles/PMC5223619). PMID 28003330 (https://pubmed.ncbi.nlm.nih.gov/28003330).
15. Ma, Wenzhe; Trusina, Ala; El-Samad, Hana; Lim, Wendell A.; Tang, Chao (2009-08-21).
"Defining network topologies that can achieve biochemical adaptation" (https://www.ncbi.nl
m.nih.gov/pmc/articles/PMC3068210). Cell. 138 (4): 760–773.
doi:10.1016/j.cell.2009.06.013 (https://doi.org/10.1016%2Fj.cell.2009.06.013). ISSN 1097-
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gov/pmc/articles/PMC3068210). PMID 19703401 (https://pubmed.ncbi.nlm.nih.gov/1970340
1).
16. Gerardin, Jaline; Reddy, Nishith R.; Lim, Wendell A. (2019-09-25). "The Design Principles of
Biochemical Timers: Circuits that Discriminate between Transient and Sustained
Stimulation" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763348). Cell Systems. 9 (3):
297–308.e2. doi:10.1016/j.cels.2019.07.008 (https://doi.org/10.1016%2Fj.cels.2019.07.008).
ISSN 2405-4720 (https://search.worldcat.org/issn/2405-4720). PMC 6763348 (https://www.n
cbi.nlm.nih.gov/pmc/articles/PMC6763348). PMID 31521602 (https://pubmed.ncbi.nlm.nih.g
ov/31521602).
17. Chau, Angela H.; Walter, Jessica M.; Gerardin, Jaline; Tang, Chao; Lim, Wendell A. (2012-
10-12). "Designing synthetic regulatory networks capable of self-organizing cell polarization"
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498761). Cell. 151 (2): 320–332.
doi:10.1016/j.cell.2012.08.040 (https://doi.org/10.1016%2Fj.cell.2012.08.040). ISSN 1097-
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gov/pmc/articles/PMC3498761). PMID 23039994 (https://pubmed.ncbi.nlm.nih.gov/2303999
4).
18. Toda, Satoshi; Blauch, Lucas R.; Tang, Sindy K. Y.; Morsut, Leonardo; Lim, Wendell A.
(2018-07-13). "Programming self-organizing multicellular structures with synthetic cell-cell
signaling" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492944). Science. 361 (6398):
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19. Toda, Satoshi; McKeithan, Wesley L.; Hakkinen, Teemu J.; Lopez, Pilar; Klein, Ophir D.;
Lim, Wendell A. (2020-10-16). "Engineering synthetic morphogen systems that can program
multicellular patterning" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986291). Science.
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20. Lim, Wendell A. (June 2010). "Designing customized cell signalling circuits" (https://www.ncb
i.nlm.nih.gov/pmc/articles/PMC2975372). Nature Reviews. Molecular Cell Biology. 11 (6):
393–403. doi:10.1038/nrm2904 (https://doi.org/10.1038%2Fnrm2904). ISSN 1471-0080 (htt
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articles/PMC2975372). PMID 20485291 (https://pubmed.ncbi.nlm.nih.gov/20485291).
21. Fischbach, Michael A.; Bluestone, Jeffrey A.; Lim, Wendell A. (2013-04-03). "Cell-Based
Therapeutics: The Next Pillar of Medicine" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3
772767). Science Translational Medicine. 5 (179): 179ps7.
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cbi.nlm.nih.gov/pmc/articles/PMC3772767). PMID 23552369 (https://pubmed.ncbi.nlm.nih.g
ov/23552369).
22. Wu, Chia-Yung; Roybal, Kole T.; Puchner, Elias M.; Onuffer, James; Lim, Wendell A. (2015-
10-16). "Remote control of therapeutic T cells through a small molecule-gated chimeric
receptor" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721629). Science. 350 (6258):
aab4077. Bibcode:2015Sci...350.4077W (https://ui.adsabs.harvard.edu/abs/2015Sci...350.4
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cbi.nlm.nih.gov/pmc/articles/PMC4721629). PMID 26405231 (https://pubmed.ncbi.nlm.nih.g
ov/26405231).
23. Morsut, Leonardo; Roybal, Kole T.; Xiong, Xin; Gordley, Russell M.; Coyle, Scott M.;
Thomson, Matthew; Lim, Wendell A. (2016-02-11). "Engineering Customized Cell Sensing
and Response Behaviors Using Synthetic Notch Receptors" (https://www.ncbi.nlm.nih.gov/p
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24. Roybal, Kole T.; Rupp, Levi J.; Morsut, Leonardo; Walker, Whitney J.; McNally, Krista A.;
Park, Jason S.; Lim, Wendell A. (2016-02-11). "Precision Tumor Recognition by T Cells With
Combinatorial Antigen-Sensing Circuits" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC475
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25. Roybal, Kole T.; Williams, Jasper Z.; Morsut, Leonardo; Rupp, Levi J.; Kolinko, Isabel; Choe,
Joseph H.; Walker, Whitney J.; McNally, Krista A.; Lim, Wendell A. (2016-10-06).
"Engineering T Cells with Customized Therapeutic Response Programs Using Synthetic
Notch Receptors" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072533). Cell. 167 (2):
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ISSN 1097-4172 (https://search.worldcat.org/issn/1097-4172). PMC 5072533 (https://www.n
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26. Williams, Jasper Z.; Allen, Greg M.; Shah, Devan; Sterin, Igal S.; Kim, Ki H.; Garcia, Vivian
P.; Shavey, Gavin E.; Yu, Wei; Puig-Saus, Cristina; Tsoi, Jennifer; Ribas, Antoni (2020-11-
27). "Precise T cell recognition programs designed by transcriptionally linking multiple
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ISSN 1095-9203 (https://search.worldcat.org/issn/1095-9203). PMC 8054651 (https://www.n
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27. Choe, Joseph H.; Watchmaker, Payal B.; Simic, Milos S.; Gilbert, Ryan D.; Li, Aileen W.;
Krasnow, Nira A.; Downey, Kira M.; Yu, Wei; Carrera, Diego A.; Celli, Anna; Cho, Juhyun
(2021-04-28). "SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and
persistence in treating glioblastoma" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC836233
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w.ncbi.nlm.nih.gov/pmc/articles/PMC3068207). Nature. 468 (7326): 889–890.
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External links
 His Academic Bio (http://profiles.ucsf.edu/ProfileDetails.aspx?Person=4594015)
His Howard Hughes Medical Institute bio (http://www.hhmi.org/research/investigators/lim_bi
o.html)
Lim Lab website (http://limlab.ucsf.edu/)

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