Wendell Lim is an American biochemist who is the Byer's Distinguished
Professor of Cellular and Molecular Pharmacology at the
University of California, San Francisco .
[2] He is the director of the UCSF Cell Design Institute.
[3] He earned his A.B. in
chemistry from
Harvard University working with
Jeremy Knowles on enzyme evolutionary optimization. He obtained his Ph.D in
biochemistry and
biophysics from
Massachusetts Institute of Technology under the guidance of
Bob Sauer using
genetic and biophysical approaches to understand the role of
hydrophobic core interactions in
protein folding .
[4] He then did his
postdoctoral work with
Frederic Richards at
Yale 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
References
^
"Fred Richards on Academic Tree" .
^
"UCSF Profiles" .
^
"UCSF Cell Design Institute" . UCSF Cell Design Institute . Retrieved 2022-07-28 .
^
"Wendell Lim" . Retrieved 1 November 2012 .
^
"Wendell A. Lim, Ph.D." HHMI. Retrieved 1 November 2012 .
^
a
b
c
d Sedwick, C. (17 September 2012).
"Wendell Lim: Exploring the path not chosen" . The Journal of Cell Biology . 198 (6): 956–957.
doi :
10.1083/jcb.1986pi .
PMC
3444780 .
PMID
22986491 .
^
"Research | Lim Lab" . limlab.ucsf.edu . Retrieved 2022-07-29 .
^ Park, Sang-Hyun; Zarrinpar, Ali; Lim, Wendell A. (2003-02-14).
"Rewiring MAP kinase pathways using alternative scaffold assembly mechanisms" . Science . 299 (5609): 1061–1064.
Bibcode :
2003Sci...299.1061P .
doi :
10.1126/science.1076979 .
ISSN
1095-9203 .
PMID
12511654 .
S2CID
1643040 .
^ Dueber, John E.; Mirsky, Ethan A.; Lim, Wendell A. (June 2007).
"Engineering synthetic signaling proteins with ultrasensitive input/output control" . Nature Biotechnology . 25 (6): 660–662.
doi :
10.1038/nbt1308 .
ISSN
1087-0156 .
PMID
17515908 .
S2CID
10465894 .
^ 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" . Nature . 447 (7144): 596–600.
Bibcode :
2007Natur.447..596Y .
doi :
10.1038/nature05851 .
ISSN
1476-4687 .
PMID
17515921 .
S2CID
4393136 .
^ 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" . Science . 319 (5869): 1539–1543.
Bibcode :
2008Sci...319.1539B .
doi :
10.1126/science.1151153 .
ISSN
1095-9203 .
PMID
18339942 .
S2CID
365578 .
^ 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" . Nature . 461 (7266): 997–1001.
Bibcode :
2009Natur.461..997L .
doi :
10.1038/nature08446 .
ISSN
1476-4687 .
PMC
2989900 .
PMID
19749742 .
^ 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" . Cell . 155 (6): 1422–1434.
doi :
10.1016/j.cell.2013.11.004 .
ISSN
1097-4172 .
PMC
3925772 .
PMID
24315106 .
^ Bugaj, Lukasz J.; O'Donoghue, Geoff P.; Lim, Wendell A. (2017-01-02).
"Interrogating cellular perception and decision making with optogenetic tools" . The Journal of Cell Biology . 216 (1): 25–28.
doi :
10.1083/jcb.201612094 .
ISSN
1540-8140 .
PMC
5223619 .
PMID
28003330 .
^ Ma, Wenzhe; Trusina, Ala; El-Samad, Hana; Lim, Wendell A.; Tang, Chao (2009-08-21).
"Defining network topologies that can achieve biochemical adaptation" . Cell . 138 (4): 760–773.
doi :
10.1016/j.cell.2009.06.013 .
ISSN
1097-4172 .
PMC
3068210 .
PMID
19703401 .
^ 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" . Cell Systems . 9 (3): 297–308.e2.
doi :
10.1016/j.cels.2019.07.008 .
ISSN
2405-4720 .
PMC
6763348 .
PMID
31521602 .
^ 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" . Cell . 151 (2): 320–332.
doi :
10.1016/j.cell.2012.08.040 .
ISSN
1097-4172 .
PMC
3498761 .
PMID
23039994 .
^
a
b
c 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" . Science . 361 (6398): 156–162.
Bibcode :
2018Sci...361..156T .
doi :
10.1126/science.aat0271 .
ISSN
1095-9203 .
PMC
6492944 .
PMID
29853554 .
^ 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" . Science . 370 (6514): 327–331.
Bibcode :
2020Sci...370..327T .
doi :
10.1126/science.abc0033 .
ISSN
1095-9203 .
PMC
7986291 .
PMID
33060357 .
^ Lim, Wendell A. (June 2010).
"Designing customized cell signalling circuits" . Nature Reviews. Molecular Cell Biology . 11 (6): 393–403.
doi :
10.1038/nrm2904 .
ISSN
1471-0080 .
PMC
2975372 .
PMID
20485291 .
^ Fischbach, Michael A.; Bluestone, Jeffrey A.; Lim, Wendell A. (2013-04-03).
"Cell-Based Therapeutics: The Next Pillar of Medicine" . Science Translational Medicine . 5 (179): 179ps7.
doi :
10.1126/scitranslmed.3005568 .
ISSN
1946-6234 .
PMC
3772767 .
PMID
23552369 .
^ 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" . Science . 350 (6258): aab4077.
Bibcode :
2015Sci...350.4077W .
doi :
10.1126/science.aab4077 .
ISSN
1095-9203 .
PMC
4721629 .
PMID
26405231 .
^ 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" . Cell . 164 (4): 780–791.
doi :
10.1016/j.cell.2016.01.012 .
ISSN
1097-4172 .
PMC
4752866 .
PMID
26830878 .
^
a
b 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" . Cell . 164 (4): 770–779.
doi :
10.1016/j.cell.2016.01.011 .
ISSN
1097-4172 .
PMC
4752902 .
PMID
26830879 .
^
a
b 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" . Cell . 167 (2): 419–432.e16.
doi :
10.1016/j.cell.2016.09.011 .
ISSN
1097-4172 .
PMC
5072533 .
PMID
27693353 .
^ 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 receptors" . Science . 370 (6520): 1099–1104.
Bibcode :
2020Sci...370.1099W .
doi :
10.1126/science.abc6270 .
ISSN
1095-9203 .
PMC
8054651 .
PMID
33243890 .
^ 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" . Science Translational Medicine . 13 (591): eabe7378.
doi :
10.1126/scitranslmed.abe7378 .
ISSN
1946-6242 .
PMC
8362330 .
PMID
33910979 .
^
a
b Elowitz, Michael; Lim, Wendell A. (December 2010).
"Build life to understand it" . Nature . 468 (7326): 889–890.
Bibcode :
2010Natur.468..889E .
doi :
10.1038/468889a .
ISSN
1476-4687 .
PMC
3068207 .
PMID
21164460 .
^ Qi, Lei S.; Larson, Matthew H.; Gilbert, Luke A.; Doudna, Jennifer A.; Weissman, Jonathan S.; Arkin, Adam P.; Lim, Wendell A. (2021-02-04).
"Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression" . Cell . 184 (3): 844.
doi :
10.1016/j.cell.2021.01.019 .
ISSN
1097-4172 .
PMID
33545038 .
S2CID
231809613 .
^
"Startup Science | UCSF Magazine" . magazine.ucsf.edu . Retrieved 2022-07-29 .
^ Thorner, Jeremy (2017-03-01).
"Cell Signaling: Principles and Mechanisms by Wendell Lim, Bruce Mayer, and Tony Pawson" . The Quarterly Review of Biology . 92 (1): 105–106.
doi :
10.1086/690882 .
ISSN
0033-5770 .
^ Tansey, Bernadette (2007-11-17).
"High school biowizards break new ground in winning competition" . SFGATE . Retrieved 2022-07-29 .
^ Zachary, G. Pascal (2007-11-18).
"English, Algebra, Phys Ed ... and Biotech" . The New York Times .
ISSN
0362-4331 . Retrieved 2022-07-29 .
^ Bernstein, Rachel (2011-10-28).
"Drop that Pipette: Science by Design" . Cell . 147 (3): 496–497.
doi :
10.1016/j.cell.2011.10.010 .
ISSN
0092-8674 .
PMID
22036559 .
S2CID
13248964 .
^
"UCSF Lecture Takes on the Science of Food | UC San Francisco" . www.ucsf.edu . Retrieved 2022-07-29 .
^
"University of Chicago Laboratory Schools: Alumni » Alumni Weekend » Rising Star Professional Achievement Award" . 2014-11-11. Archived from
the original on 2014-11-11. Retrieved 2022-07-29 .
^
"15th CeMM Landsteiner Lecture by Wendell Lim and the 2021 Denise P. Barlow Award Ceremony" . CeMM - Science is our medicine! . Retrieved 2022-07-29 .
^
"Wendell Lim, selected for the 34th George Streisinger Memorial Lecture | Center for Cellular Construction" . ccc.ucsf.edu . Retrieved 2022-07-29 .
^
"Feodor Lynen Lecture & Medaille - Homepage der Gesellschaft für Biochemie und Molekularbiologie e.V." gbm-online.de . Retrieved 2022-07-29 .
^
"NIH Director's Transformative Research Award Program - Funded Research" . commonfund.nih.gov . 2013-06-27. Retrieved 2022-07-29 .
^
"The Smart List 2012: 50 people who will change the world" . Wired UK .
ISSN
1357-0978 . Retrieved 2022-07-29 .
^
"Wendell A. Lim" . HHMI . Retrieved 2022-07-29 .
^
"The Protein Society : Protein Society Awards" . www.proteinsociety.org . Retrieved 2022-07-29 .
^
"Science Talent Search 1982" . Society for Science . Retrieved 2022-07-29 .
^
"Wendell Lim, Ph.D." www.science.org . Retrieved 2022-07-29 .
^
"Editorial board: Cell" . www.cell.com . Retrieved 2022-07-29 .
^
"BWF Board" . Burroughs Wellcome Fund . Retrieved 2022-07-29 .
External links
International National Academics Other