Wendell Lim

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. He is the director of the UCSF Cell Design Institute. 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. He then did his postdoctoral work with Frederic Richards at Yale University on the structure of protein interaction domains. Lim's work has focused on cell signaling, synthetic biology, and cell engineering, particularly in immune cells.

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 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. 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. He has been applying these approaches to engineer and understand immune cell function as well as multicellular self-organization (synthetic development).

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. His group was the first to develop small molecule gated chimeric antigen receptors (CARs) as well as the highly flexible synthetic Notch (synNotch) receptor platform for programming novel transcriptional control circuits. 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). His group has also engineered T cells to recognize specific target tissues, and to deliver genetically encoded therapeutic payloads to these sites.

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. He has also been engineering multicellular networks that drive specific formation of complex self-organizing tissue-like structures.

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

Personal life Lim is Chinese-American and grew up in Chicago, where he graduated from the University of Chicago Laboratory Schools. He currently lives in San Francisco with his wife and children. Lim is an avid basketball player, surfer, and artist. University of Oregon, Streisinger Lecture (2020) German Biochemical Society, Feodor Lynden Award (2019) NIH Transformative R01 ('Re-Designing the T cell') (2014) Wired Magazine, 50 people who will change the world (2012) Howard Hughes Medical Institute Investigator (2008–2020) Protein Society Hans Neurath Award (2010) Westinghouse Science Talent Search Finalist (1982) Editorial Board, Science Magazine Editorial Board, Cell Burroughs Wellcome Fund, Board of Directors