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Wendell Lim

{{Infobox scientist

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| nationality = American

| fields = Bioengineering

| workplaces = University of California, San Francisco

| alma_mater = Harvard University, Massachusetts Institute of Technology

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| academic_advisors = Fred Richards{{cite web|url=http://academictree.org/chemistry/peopleinfo.php?pid=53842|title=Fred Richards on Academic Tree}}

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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.{{Cite web |title=UCSF Profiles |url=https://profiles.ucsf.edu/wendell.lim }} He is the director of the UCSF Cell Design Institute.{{Cite web |title=UCSF Cell Design Institute |url=https://www.celldesigninstitute.org/ |access-date=2022-07-28 |website=UCSF Cell Design Institute |language=en-US}} 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.{{cite web|title=Wendell Lim|url=http://mit.edu/sauerlab/publalumnithree.html#WLim|accessdate=1 November 2012}} He then did his postdoctoral work with Frederic Richards at Yale University on the structure of protein interaction domains.{{cite web|title=Wendell A. Lim, Ph.D.|url=http://www.hhmi.org/news/lim_bio.html|publisher=HHMI|accessdate=1 November 2012}}{{cite journal |last=Sedwick |first=C. |date=17 September 2012 |title=Wendell Lim: Exploring the path not chosen |journal=The Journal of Cell Biology |volume=198 |issue=6 |pages=956–957 |doi=10.1083/jcb.1986pi |pmc=3444780 |pmid=22986491}} Lim's work has focused on cell signaling, synthetic biology, and cell engineering, particularly in immune cells.{{Cite web |title=Research {{!}} Lim Lab |url=https://limlab.ucsf.edu/research.html |access-date=2022-07-29 |website=limlab.ucsf.edu}}

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. 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.

= 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.{{Cite journal |last1=Park |first1=Sang-Hyun |last2=Zarrinpar |first2=Ali |last3=Lim |first3=Wendell A. |date=2003-02-14 |title=Rewiring MAP kinase pathways using alternative scaffold assembly mechanisms |url=https://pubmed.ncbi.nlm.nih.gov/12511654/ |journal=Science |volume=299 |issue=5609 |pages=1061–1064 |doi=10.1126/science.1076979 |issn=1095-9203 |pmid=12511654|bibcode=2003Sci...299.1061P |s2cid=1643040 |doi-access=free }}{{Cite journal |last1=Dueber |first1=John E. |last2=Mirsky |first2=Ethan A. |last3=Lim |first3=Wendell A. |date=June 2007 |title=Engineering synthetic signaling proteins with ultrasensitive input/output control |url=https://pubmed.ncbi.nlm.nih.gov/17515908/ |journal=Nature Biotechnology |volume=25 |issue=6 |pages=660–662 |doi=10.1038/nbt1308 |issn=1087-0156 |pmid=17515908|s2cid=10465894 }}{{Cite journal |last1=Yeh |first1=Brian J. |last2=Rutigliano |first2=Robert J. |last3=Deb |first3=Anrica |last4=Bar-Sagi |first4=Dafna |last5=Lim |first5=Wendell A. |date=2007-05-31 |title=Rewiring cellular morphology pathways with synthetic guanine nucleotide exchange factors |url=https://pubmed.ncbi.nlm.nih.gov/17515921/ |journal=Nature |volume=447 |issue=7144 |pages=596–600 |doi=10.1038/nature05851 |issn=1476-4687 |pmid=17515921|bibcode=2007Natur.447..596Y |s2cid=4393136 }}{{Cite journal |last1=Bashor |first1=Caleb J. |last2=Helman |first2=Noah C. |last3=Yan |first3=Shude |last4=Lim |first4=Wendell A. |date=2008-03-14 |title=Using engineered scaffold interactions to reshape MAP kinase pathway signaling dynamics |url=https://pubmed.ncbi.nlm.nih.gov/18339942/ |journal=Science |volume=319 |issue=5869 |pages=1539–1543 |doi=10.1126/science.1151153 |issn=1095-9203 |pmid=18339942|bibcode=2008Sci...319.1539B |s2cid=365578 }} 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.{{Cite journal |last1=Levskaya |first1=Anselm |last2=Weiner |first2=Orion D. |last3=Lim |first3=Wendell A. |last4=Voigt |first4=Christopher A. |date=2009-10-15 |title=Spatiotemporal control of cell signalling using a light-switchable protein interaction |journal=Nature |volume=461 |issue=7266 |pages=997–1001 |doi=10.1038/nature08446 |issn=1476-4687 |pmc=2989900 |pmid=19749742|bibcode=2009Natur.461..997L }}{{Cite journal |last1=Toettcher |first1=Jared E. |last2=Weiner |first2=Orion D. |last3=Lim |first3=Wendell A. |date=2013-12-05 |title=Using optogenetics to interrogate the dynamic control of signal transmission by the Ras/Erk module |journal=Cell |volume=155 |issue=6 |pages=1422–1434 |doi=10.1016/j.cell.2013.11.004 |issn=1097-4172 |pmc=3925772 |pmid=24315106}}{{Cite journal |last1=Bugaj |first1=Lukasz J. |last2=O'Donoghue |first2=Geoff P. |last3=Lim |first3=Wendell A. |date=2017-01-02 |title=Interrogating cellular perception and decision making with optogenetic tools |journal=The Journal of Cell Biology |volume=216 |issue=1 |pages=25–28 |doi=10.1083/jcb.201612094 |issn=1540-8140 |pmc=5223619 |pmid=28003330}} 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.{{Cite journal |last1=Ma |first1=Wenzhe |last2=Trusina |first2=Ala |last3=El-Samad |first3=Hana |last4=Lim |first4=Wendell A. |last5=Tang |first5=Chao |date=2009-08-21 |title=Defining network topologies that can achieve biochemical adaptation |journal=Cell |volume=138 |issue=4 |pages=760–773 |doi=10.1016/j.cell.2009.06.013 |issn=1097-4172 |pmc=3068210 |pmid=19703401}}{{Cite journal |last1=Gerardin |first1=Jaline |last2=Reddy |first2=Nishith R. |last3=Lim |first3=Wendell A. |date=2019-09-25 |title=The Design Principles of Biochemical Timers: Circuits that Discriminate between Transient and Sustained Stimulation |journal=Cell Systems |volume=9 |issue=3 |pages=297–308.e2 |doi=10.1016/j.cels.2019.07.008 |issn=2405-4720 |pmc=6763348 |pmid=31521602}}{{Cite journal |last1=Chau |first1=Angela H. |last2=Walter |first2=Jessica M. |last3=Gerardin |first3=Jaline |last4=Tang |first4=Chao |last5=Lim |first5=Wendell A. |date=2012-10-12 |title=Designing synthetic regulatory networks capable of self-organizing cell polarization |journal=Cell |volume=151 |issue=2 |pages=320–332 |doi=10.1016/j.cell.2012.08.040 |issn=1097-4172 |pmc=3498761 |pmid=23039994}}{{Cite journal |last1=Toda |first1=Satoshi |last2=Blauch |first2=Lucas R. |last3=Tang |first3=Sindy K. Y. |last4=Morsut |first4=Leonardo |last5=Lim |first5=Wendell A. |date=2018-07-13 |title=Programming self-organizing multicellular structures with synthetic cell-cell signaling |journal=Science |volume=361 |issue=6398 |pages=156–162 |doi=10.1126/science.aat0271 |issn=1095-9203 |pmc=6492944 |pmid=29853554|bibcode=2018Sci...361..156T }} He has been applying these approaches to engineer and understand immune cell function as well as multicellular self-organization (synthetic development).{{Cite journal |last1=Toda |first1=Satoshi |last2=McKeithan |first2=Wesley L. |last3=Hakkinen |first3=Teemu J. |last4=Lopez |first4=Pilar |last5=Klein |first5=Ophir D. |last6=Lim |first6=Wendell A. |date=2020-10-16 |title=Engineering synthetic morphogen systems that can program multicellular patterning |journal=Science |volume=370 |issue=6514 |pages=327–331 |doi=10.1126/science.abc0033 |issn=1095-9203 |pmc=7986291 |pmid=33060357|bibcode=2020Sci...370..327T }}

= 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.{{Cite journal |last=Lim |first=Wendell A. |date=June 2010 |title=Designing customized cell signalling circuits |journal=Nature Reviews. Molecular Cell Biology |volume=11 |issue=6 |pages=393–403 |doi=10.1038/nrm2904 |issn=1471-0080 |pmc=2975372 |pmid=20485291}}{{Cite journal |last1=Fischbach |first1=Michael A. |last2=Bluestone |first2=Jeffrey A. |last3=Lim |first3=Wendell A. |date=2013-04-03 |title=Cell-Based Therapeutics: The Next Pillar of Medicine |journal=Science Translational Medicine |language=en |volume=5 |issue=179 |pages=179ps7 |doi=10.1126/scitranslmed.3005568 |issn=1946-6234 |pmc=3772767 |pmid=23552369}} His group was the first to develop small molecule gated chimeric antigen receptors (CARs) {{Cite journal |last1=Wu |first1=Chia-Yung |last2=Roybal |first2=Kole T. |last3=Puchner |first3=Elias M. |last4=Onuffer |first4=James |last5=Lim |first5=Wendell A. |date=2015-10-16 |title=Remote control of therapeutic T cells through a small molecule-gated chimeric receptor |journal=Science |volume=350 |issue=6258 |pages=aab4077 |doi=10.1126/science.aab4077 |issn=1095-9203 |pmc=4721629 |pmid=26405231|bibcode=2015Sci...350.4077W }} as well as the highly flexible synthetic Notch (synNotch) receptor platform for programming novel transcriptional control circuits.{{Cite journal |last1=Morsut |first1=Leonardo |last2=Roybal |first2=Kole T. |last3=Xiong |first3=Xin |last4=Gordley |first4=Russell M. |last5=Coyle |first5=Scott M. |last6=Thomson |first6=Matthew |last7=Lim |first7=Wendell A. |date=2016-02-11 |title=Engineering Customized Cell Sensing and Response Behaviors Using Synthetic Notch Receptors |journal=Cell |volume=164 |issue=4 |pages=780–791 |doi=10.1016/j.cell.2016.01.012 |issn=1097-4172 |pmc=4752866 |pmid=26830878}}{{Cite journal |last1=Roybal |first1=Kole T. |last2=Rupp |first2=Levi J. |last3=Morsut |first3=Leonardo |last4=Walker |first4=Whitney J. |last5=McNally |first5=Krista A. |last6=Park |first6=Jason S. |last7=Lim |first7=Wendell A. |date=2016-02-11 |title=Precision Tumor Recognition by T Cells With Combinatorial Antigen-Sensing Circuits |journal=Cell |volume=164 |issue=4 |pages=770–779 |doi=10.1016/j.cell.2016.01.011 |issn=1097-4172 |pmc=4752902 |pmid=26830879}}{{Cite journal |last1=Roybal |first1=Kole T. |last2=Williams |first2=Jasper Z. |last3=Morsut |first3=Leonardo |last4=Rupp |first4=Levi J. |last5=Kolinko |first5=Isabel |last6=Choe |first6=Joseph H. |last7=Walker |first7=Whitney J. |last8=McNally |first8=Krista A. |last9=Lim |first9=Wendell A. |date=2016-10-06 |title=Engineering T Cells with Customized Therapeutic Response Programs Using Synthetic Notch Receptors |journal=Cell |volume=167 |issue=2 |pages=419–432.e16 |doi=10.1016/j.cell.2016.09.011 |issn=1097-4172 |pmc=5072533 |pmid=27693353}} 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).{{Cite journal |last1=Williams |first1=Jasper Z. |last2=Allen |first2=Greg M. |last3=Shah |first3=Devan |last4=Sterin |first4=Igal S. |last5=Kim |first5=Ki H. |last6=Garcia |first6=Vivian P. |last7=Shavey |first7=Gavin E. |last8=Yu |first8=Wei |last9=Puig-Saus |first9=Cristina |last10=Tsoi |first10=Jennifer |last11=Ribas |first11=Antoni |date=2020-11-27 |title=Precise T cell recognition programs designed by transcriptionally linking multiple receptors |journal=Science |volume=370 |issue=6520 |pages=1099–1104 |doi=10.1126/science.abc6270 |issn=1095-9203 |pmc=8054651 |pmid=33243890|bibcode=2020Sci...370.1099W }}{{Cite journal |last1=Choe |first1=Joseph H. |last2=Watchmaker |first2=Payal B. |last3=Simic |first3=Milos S. |last4=Gilbert |first4=Ryan D. |last5=Li |first5=Aileen W. |last6=Krasnow |first6=Nira A. |last7=Downey |first7=Kira M. |last8=Yu |first8=Wei |last9=Carrera |first9=Diego A. |last10=Celli |first10=Anna |last11=Cho |first11=Juhyun |date=2021-04-28 |title=SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma |journal=Science Translational Medicine |volume=13 |issue=591 |pages=eabe7378 |doi=10.1126/scitranslmed.abe7378 |issn=1946-6242 |pmc=8362330 |pmid=33910979}} His group has also engineered T cells to recognize specific target tissues, and to deliver genetically encoded therapeutic payloads to these sites. In addition, Lim's group has used these synthetic receptors to design positive feedback circuits for sensing antigen density with non-linear thresholds.{{Cite journal |last1=Elowitz |first1=Michael |last2=Lim |first2=Wendell A. |date=December 2010 |title=Build life to understand it |journal=Nature |language=en |volume=468 |issue=7326 |pages=889–890 |doi=10.1038/468889a |pmid=21164460 |pmc=3068207 |bibcode=2010Natur.468..889E |issn=1476-4687}}

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.{{Cite journal |last1=Qi |first1=Lei S. |last2=Larson |first2=Matthew H. |last3=Gilbert |first3=Luke A. |last4=Doudna |first4=Jennifer A. |last5=Weissman |first5=Jonathan S. |last6=Arkin |first6=Adam P. |last7=Lim |first7=Wendell A. |date=2021-02-04 |title=Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression |url=https://pubmed.ncbi.nlm.nih.gov/33545038/ |journal=Cell |volume=184 |issue=3 |pages=844 |doi=10.1016/j.cell.2021.01.019 |issn=1097-4172 |pmid=33545038|s2cid=231809613 |doi-access=free }} He has also been engineering multicellular networks that drive specific formation of complex self-organizing tissue-like structures. 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.

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.{{Cite web |title=Startup Science {{!}} UCSF Magazine |url=https://magazine.ucsf.edu/startup-science |access-date=2022-07-29 |website=magazine.ucsf.edu |language=en}}

Science education and outreach

Lim co-authored the textbook Cell Signaling with colleagues Bruce Mayer and Tony Pawson.{{Cite journal |last=Thorner |first=Jeremy |date=2017-03-01 |title=Cell Signaling: Principles and Mechanisms by Wendell Lim, Bruce Mayer, and Tony Pawson |url=https://www.journals.uchicago.edu/doi/10.1086/690882 |journal=The Quarterly Review of Biology |volume=92 |issue=1 |pages=105–106 |doi=10.1086/690882 |issn=0033-5770|url-access=subscription }} His group has also participated in the synthetic biology outreach program iGEM with San Francisco Bay Area high school students and teachers.{{Cite web |last=Tansey |first=Bernadette |date=2007-11-17 |title=High school biowizards break new ground in winning competition |url=https://www.sfgate.com/education/article/High-school-biowizards-break-new-ground-in-3300857.php |access-date=2022-07-29 |website=SFGATE |language=en-US}}{{Cite news |last=Zachary |first=G. Pascal |date=2007-11-18 |title=English, Algebra, Phys Ed ... and Biotech |language=en-US |work=The New York Times |url=https://www.nytimes.com/2007/11/18/technology/18ping.html |access-date=2022-07-29 |issn=0362-4331}} He has also conducted creative projects on design thinking,{{Cite journal |last=Bernstein |first=Rachel |date=2011-10-28 |title=Drop that Pipette: Science by Design |url=https://www.cell.com/cell/abstract/S0092-8674(11)01208-6 |journal=Cell |language=English |volume=147 |issue=3 |pages=496–497 |doi=10.1016/j.cell.2011.10.010 |issn=0092-8674 |pmid=22036559|s2cid=13248964 |doi-access=free }} as well as science and cooking.{{Cite web |title=UCSF Lecture Takes on the Science of Food {{!}} UC San Francisco |url=https://www.ucsf.edu/news/2012/07/104227/ucsf-lecture-takes-science-food |access-date=2022-07-29 |website=www.ucsf.edu |language=en}}

Personal life

Lim is Chinese-American and grew up in Chicago, where he graduated from the University of Chicago Laboratory Schools.{{Cite web |date=2014-11-11 |title=University of Chicago Laboratory Schools: Alumni » Alumni Weekend » Rising Star Professional Achievement Award |url=http://www.ucls.uchicago.edu/alumni/alumni-weekend/young-alumni-professional-achievement-award/index.aspx |archive-url=https://web.archive.org/web/20141111093100/http://www.ucls.uchicago.edu/alumni/alumni-weekend/young-alumni-professional-achievement-award/index.aspx |archive-date=2014-11-11 |access-date=2022-07-29 }} He currently lives in San Francisco with his wife and children. Lim is an avid basketball player, surfer, and artist.

Awards and service

  • Vienna Center for Molecular Medicine, Landsteiner Lecture (2021){{Cite web |title=15th CeMM Landsteiner Lecture by Wendell Lim and the 2021 Denise P. Barlow Award Ceremony |url=https://cemm.at/news/n/15th-cemm-landsteiner-lecture-by-wendell-lim-and-the-2021-denise-p-barlow-award-ceremony |access-date=2022-07-29 |website=CeMM - Science is our medicine! |language=en-us}}
  • University of Oregon, Streisinger Lecture (2020){{Cite web |title=Wendell Lim, selected for the 34th George Streisinger Memorial Lecture {{!}} Center for Cellular Construction |url=https://ccc.ucsf.edu/news/wendell-lim-selected-34th-george-streisinger-memorial-lecture |access-date=2022-07-29 |website=ccc.ucsf.edu}}
  • German Biochemical Society, Feodor Lynden Award (2019){{Cite web |title=Feodor Lynen Lecture & Medaille - Homepage der Gesellschaft für Biochemie und Molekularbiologie e.V. |url=https://gbm-online.de/preise-und-auszeichnungen-details/feodor-lynen-lecture-medaille.html |access-date=2022-07-29 |website=gbm-online.de}}
  • NIH Transformative R01 ('Re-Designing the T cell') (2014){{Cite web |date=2013-06-27 |title=NIH Director's Transformative Research Award Program - Funded Research |url=https://commonfund.nih.gov/tra/fundedresearch |access-date=2022-07-29 |website=commonfund.nih.gov |language=en}}
  • Wired Magazine, 50 people who will change the world (2012){{Cite magazine |title=The Smart List 2012: 50 people who will change the world |language=en-GB |magazine=Wired UK |url=https://www.wired.co.uk/article/the-smart-list |access-date=2022-07-29 |issn=1357-0978}}
  • Howard Hughes Medical Institute Investigator (2008–2020){{Cite web |title=Wendell A. Lim |url=https://www.hhmi.org/scientists/wendell-lim |access-date=2022-07-29 |website=HHMI |language=en}}
  • Protein Society Hans Neurath Award (2010){{Cite web |title=The Protein Society : Protein Society Awards |url=https://www.proteinsociety.org/page/protein-society-awards |access-date=2022-07-29 |website=www.proteinsociety.org}}
  • Westinghouse Science Talent Search Finalist (1982){{Cite web |title=Science Talent Search 1982 |url=https://www.societyforscience.org/regeneron-sts/science-talent-search-1982/ |access-date=2022-07-29 |website=Society for Science |language=en-US}}
  • Editorial Board, Science Magazine{{Cite web |title=Wendell Lim, Ph.D. |url=https://www.science.org/content/author/wendell-lim-phd |access-date=2022-07-29 |website=www.science.org |language=en}}
  • Editorial Board, Cell{{Cite web |title=Editorial board: Cell |url=https://www.cell.com/cell/editorial-board |access-date=2022-07-29 |website=www.cell.com}}
  • Burroughs Wellcome Fund, Board of Directors{{Cite web |title=BWF Board |url=https://www.bwfund.org/about/board/ |access-date=2022-07-29 |website=Burroughs Wellcome Fund |language=en-US}}

References

{{Reflist}}

External links

  • [http://profiles.ucsf.edu/ProfileDetails.aspx?Person=4594015 His Academic Bio]
  • [http://www.hhmi.org/research/investigators/lim_bio.html His Howard Hughes Medical Institute bio]
  • [http://limlab.ucsf.edu/ Lim Lab website]

{{authority control}}

{{DEFAULTSORT:Lim, Wendell}}

Category:Living people

Category:American biochemists

Category:Howard Hughes Medical Investigators

Category:Place of birth missing (living people)

Category:Year of birth missing (living people)

Category:University of California, San Francisco faculty

Category:Scientists from the San Francisco Bay Area

Category:Harvard University alumni

Category:Massachusetts Institute of Technology School of Science alumni

Category:Helen Hay Whitney Foundation fellows