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Wendell Lim

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Wendell Lim
NationalityAmerican
Alma materHarvard University, Massachusetts Institute of Technology
Scientific career
FieldsBioengineering
InstitutionsUniversity of California, San Francisco
Academic advisorsFred 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

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Modular Signaling Proteins

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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

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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

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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

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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

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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

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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

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References

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  1. ^ "Fred Richards on Academic Tree".
  2. ^ "UCSF Profiles".
  3. ^ "UCSF Cell Design Institute". UCSF Cell Design Institute. Retrieved 2022-07-28.
  4. ^ "Wendell Lim". Retrieved 1 November 2012.
  5. ^ "Wendell A. Lim, Ph.D." HHMI. Retrieved 1 November 2012.
  6. ^ 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.
  7. ^ "Research | Lim Lab". 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". Science. 299 (5609): 1061–1064. Bibcode:2003Sci...299.1061P. doi:10.1126/science.1076979. ISSN 1095-9203. PMID 12511654. S2CID 1643040.
  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. doi:10.1038/nbt1308. ISSN 1087-0156. PMID 17515908. S2CID 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. Bibcode:2007Natur.447..596Y. doi:10.1038/nature05851. ISSN 1476-4687. PMID 17515921. S2CID 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. Bibcode:2008Sci...319.1539B. doi:10.1126/science.1151153. ISSN 1095-9203. PMID 18339942. S2CID 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. Bibcode:2009Natur.461..997L. doi:10.1038/nature08446. ISSN 1476-4687. PMC 2989900. PMID 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". Cell. 155 (6): 1422–1434. doi:10.1016/j.cell.2013.11.004. ISSN 1097-4172. PMC 3925772. PMID 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. doi:10.1083/jcb.201612094. ISSN 1540-8140. PMC 5223619. PMID 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. doi:10.1016/j.cell.2009.06.013. ISSN 1097-4172. PMC 3068210. PMID 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. doi:10.1016/j.cels.2019.07.008. ISSN 2405-4720. PMC 6763348. PMID 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. doi:10.1016/j.cell.2012.08.040. ISSN 1097-4172. PMC 3498761. PMID 23039994.
  18. ^ 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.
  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. Bibcode:2020Sci...370..327T. doi:10.1126/science.abc0033. ISSN 1095-9203. PMC 7986291. PMID 33060357.
  20. ^ 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.
  21. ^ 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.
  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. Bibcode:2015Sci...350.4077W. doi:10.1126/science.aab4077. ISSN 1095-9203. PMC 4721629. PMID 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". Cell. 164 (4): 780–791. doi:10.1016/j.cell.2016.01.012. ISSN 1097-4172. PMC 4752866. PMID 26830878.
  24. ^ 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.
  25. ^ 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.
  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. Bibcode:2020Sci...370.1099W. doi:10.1126/science.abc6270. ISSN 1095-9203. PMC 8054651. PMID 33243890.
  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. doi:10.1126/scitranslmed.abe7378. ISSN 1946-6242. PMC 8362330. PMID 33910979.
  28. ^ 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.
  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. doi:10.1016/j.cell.2021.01.019. ISSN 1097-4172. PMID 33545038. S2CID 231809613.
  30. ^ "Startup Science | UCSF Magazine". magazine.ucsf.edu. Retrieved 2022-07-29.
  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. doi:10.1086/690882. ISSN 0033-5770.
  32. ^ Tansey, Bernadette (2007-11-17). "High school biowizards break new ground in winning competition". SFGATE. Retrieved 2022-07-29.
  33. ^ Zachary, G. Pascal (2007-11-18). "English, Algebra, Phys Ed ... and Biotech". The New York Times. ISSN 0362-4331. Retrieved 2022-07-29.
  34. ^ 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.
  35. ^ "UCSF Lecture Takes on the Science of Food | UC San Francisco". www.ucsf.edu. Retrieved 2022-07-29.
  36. ^ "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.
  37. ^ "15th CeMM Landsteiner Lecture by Wendell Lim and the 2021 Denise P. Barlow Award Ceremony". CeMM - Science is our medicine!. Retrieved 2022-07-29.
  38. ^ "Wendell Lim, selected for the 34th George Streisinger Memorial Lecture | Center for Cellular Construction". ccc.ucsf.edu. Retrieved 2022-07-29.
  39. ^ "Feodor Lynen Lecture & Medaille - Homepage der Gesellschaft für Biochemie und Molekularbiologie e.V." gbm-online.de. Retrieved 2022-07-29.
  40. ^ "NIH Director's Transformative Research Award Program - Funded Research". commonfund.nih.gov. 2013-06-27. Retrieved 2022-07-29.
  41. ^ "The Smart List 2012: 50 people who will change the world". Wired UK. ISSN 1357-0978. Retrieved 2022-07-29.
  42. ^ "Wendell A. Lim". HHMI. Retrieved 2022-07-29.
  43. ^ "The Protein Society : Protein Society Awards". www.proteinsociety.org. Retrieved 2022-07-29.
  44. ^ "Science Talent Search 1982". Society for Science. Retrieved 2022-07-29.
  45. ^ "Wendell Lim, Ph.D." www.science.org. Retrieved 2022-07-29.
  46. ^ "Editorial board: Cell". www.cell.com. Retrieved 2022-07-29.
  47. ^ "BWF Board". Burroughs Wellcome Fund. Retrieved 2022-07-29.
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