Wendell Lim Explained

Wendell Lim
Nationality:American
Fields:Bioengineering
Workplaces:University of California, San Francisco
Alma Mater:Harvard University, Massachusetts Institute of Technology
Academic Advisors:Fred Richards[1]

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. 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.[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).[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).[26] [27] 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.[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. 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.

Awards and service

External links

Notes and References

  1. Web site: Fred Richards on Academic Tree.
  2. Web site: UCSF Profiles .
  3. Web site: UCSF Cell Design Institute . 2022-07-28 . UCSF Cell Design Institute . en-US.
  4. Web site: Wendell Lim. 1 November 2012.
  5. Web site: Wendell A. Lim, Ph.D.. HHMI. 1 November 2012.
  6. Sedwick . C. . 17 September 2012 . Wendell Lim: Exploring the path not chosen . The Journal of Cell Biology . 198 . 6 . 956–957 . 10.1083/jcb.1986pi . 3444780 . 22986491.
  7. Web site: Research Lim Lab . 2022-07-29 . limlab.ucsf.edu.
  8. 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 . 10.1126/science.1076979 . 1095-9203 . 12511654. 2003Sci...299.1061P . 1643040 . free .
  9. 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 . 10.1038/nbt1308 . 1087-0156 . 17515908. 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 . Nature . 447 . 7144 . 596–600 . 10.1038/nature05851 . 1476-4687 . 17515921. 2007Natur.447..596Y . 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 . Science . 319 . 5869 . 1539–1543 . 10.1126/science.1151153 . 1095-9203 . 18339942. 2008Sci...319.1539B . 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 . Nature . 461 . 7266 . 997–1001 . 10.1038/nature08446 . 1476-4687 . 2989900 . 19749742. 2009Natur.461..997L .
  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 . Cell . 155 . 6 . 1422–1434 . 10.1016/j.cell.2013.11.004 . 1097-4172 . 3925772 . 24315106.
  14. 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 . 10.1083/jcb.201612094 . 1540-8140 . 5223619 . 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 . Cell . 138 . 4 . 760–773 . 10.1016/j.cell.2009.06.013 . 1097-4172 . 3068210 . 19703401.
  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 . Cell Systems . 9 . 3 . 297–308.e2 . 10.1016/j.cels.2019.07.008 . 2405-4720 . 6763348 . 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 . Cell . 151 . 2 . 320–332 . 10.1016/j.cell.2012.08.040 . 1097-4172 . 3498761 . 23039994.
  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 . Science . 361 . 6398 . 156–162 . 10.1126/science.aat0271 . 1095-9203 . 6492944 . 29853554. 2018Sci...361..156T .
  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 . Science . 370 . 6514 . 327–331 . 10.1126/science.abc0033 . 1095-9203 . 7986291 . 33060357. 2020Sci...370..327T .
  20. Lim . Wendell A. . June 2010 . Designing customized cell signalling circuits . Nature Reviews. Molecular Cell Biology . 11 . 6 . 393–403 . 10.1038/nrm2904 . 1471-0080 . 2975372 . 20485291.
  21. Fischbach . Michael A. . Bluestone . Jeffrey A. . Lim . Wendell A. . 2013-04-03 . Cell-Based Therapeutics: The Next Pillar of Medicine . Science Translational Medicine . en . 5 . 179 . 179ps7 . 10.1126/scitranslmed.3005568 . 1946-6234 . 3772767 . 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 . Science . 350 . 6258 . aab4077 . 10.1126/science.aab4077 . 1095-9203 . 4721629 . 26405231. 2015Sci...350.4077W .
  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 . Cell . 164 . 4 . 780–791 . 10.1016/j.cell.2016.01.012 . 1097-4172 . 4752866 . 26830878.
  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 . Cell . 164 . 4 . 770–779 . 10.1016/j.cell.2016.01.011 . 1097-4172 . 4752902 . 26830879.
  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 . Cell . 167 . 2 . 419–432.e16 . 10.1016/j.cell.2016.09.011 . 1097-4172 . 5072533 . 27693353.
  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 receptors . Science . 370 . 6520 . 1099–1104 . 10.1126/science.abc6270 . 1095-9203 . 8054651 . 33243890. 2020Sci...370.1099W .
  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 . Science Translational Medicine . 13 . 591 . eabe7378 . 10.1126/scitranslmed.abe7378 . 1946-6242 . 8362330 . 33910979.
  28. Elowitz . Michael . Lim . Wendell A. . December 2010 . Build life to understand it . Nature . en . 468 . 7326 . 889–890 . 10.1038/468889a . 21164460 . 3068207 . 2010Natur.468..889E . 1476-4687.
  29. 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 . 10.1016/j.cell.2021.01.019 . 1097-4172 . 33545038. 231809613 . free .
  30. Web site: Startup Science UCSF Magazine . 2022-07-29 . magazine.ucsf.edu . en.
  31. 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 . 10.1086/690882 . 0033-5770.
  32. Web site: Tansey . Bernadette . 2007-11-17 . High school biowizards break new ground in winning competition . 2022-07-29 . SFGATE . en-US.
  33. News: Zachary . G. Pascal . 2007-11-18 . English, Algebra, Phys Ed ... and Biotech . en-US . The New York Times . 2022-07-29 . 0362-4331.
  34. Bernstein . Rachel . 2011-10-28 . Drop that Pipette: Science by Design . Cell . English . 147 . 3 . 496–497 . 10.1016/j.cell.2011.10.010 . 0092-8674 . 22036559. 13248964 . free .
  35. Web site: UCSF Lecture Takes on the Science of Food UC San Francisco . 2022-07-29 . www.ucsf.edu . en.
  36. Web site: 2014-11-11 . University of Chicago Laboratory Schools: Alumni » Alumni Weekend » Rising Star Professional Achievement Award . https://web.archive.org/web/20141111093100/http://www.ucls.uchicago.edu/alumni/alumni-weekend/young-alumni-professional-achievement-award/index.aspx . 2014-11-11 . 2022-07-29 .
  37. Web site: 15th CeMM Landsteiner Lecture by Wendell Lim and the 2021 Denise P. Barlow Award Ceremony . 2022-07-29 . CeMM - Science is our medicine! . en-us.
  38. Web site: Wendell Lim, selected for the 34th George Streisinger Memorial Lecture Center for Cellular Construction . 2022-07-29 . ccc.ucsf.edu.
  39. Web site: Feodor Lynen Lecture & Medaille - Homepage der Gesellschaft für Biochemie und Molekularbiologie e.V. . 2022-07-29 . gbm-online.de.
  40. Web site: 2013-06-27 . NIH Director's Transformative Research Award Program - Funded Research . 2022-07-29 . commonfund.nih.gov . en.
  41. The Smart List 2012: 50 people who will change the world . en-GB . Wired UK . 2022-07-29 . 1357-0978.
  42. Web site: Wendell A. Lim . 2022-07-29 . HHMI . en.
  43. Web site: The Protein Society : Protein Society Awards . 2022-07-29 . www.proteinsociety.org.
  44. Web site: Science Talent Search 1982 . 2022-07-29 . Society for Science . en-US.
  45. Web site: Wendell Lim, Ph.D. . 2022-07-29 . www.science.org . en.
  46. Web site: Editorial board: Cell . 2022-07-29 . www.cell.com.
  47. Web site: BWF Board . 2022-07-29 . Burroughs Wellcome Fund . en-US.

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