Lim Lab
Principal Investigator: Wendell A Lim
Institution: University of California, San Francisco (San Francisco, CA)
Primary Subfield: Molecular & Cell Bio
Recruitment Status: ✅ Accepting PhD Students ✅ Hiring Postdocs
Research Focus
PROJECT SUMMARY Cellular differentiation is controlled by epigenetic regulatory systems that integrate multiple sensory inputs over time to direct long-term cell fate decisions. Harnessing epigenetic regulation in the design of synthetic gene circuits would greatly augment synthetic biology. Synthetic epigenetic circuits based on controlling chromatin state present many attractive advantages over current forms of artificial cellular memory (e.g. recombinase or Cas9-based switches/cascades) which can be limited in scalability, stability, and temporal control. Natural epigenetic systems support stable memory states without altering genetic information, can induce state changes in either deterministic or stochastic fashion, and still maintain reversibility. We propose to generate a synthetic toolbox to regulate chromatin state in response to user-specified inputs, thereby allowing construction of circuits with key epigenetic properties, such as memory, fate bifurcation and temporally controlled gene expression. Our proposed circuits will be designed to a) respond to a variety of extracellular input cues through synthetic Notch receptors, b) discriminate inputs by duration to specifica…
Active NIH Awards
- 5R01CA253017-06: Synthetic epigenetic circuits: tunable cell fate switches controlled by dynamic and combinatorial inputs (2026)
- 5R01CA249018-06: Recognizing the tumor ecosystem: Integrating stromal and cancer antigen signals to achieve precision recognition of solid tumors by CAR T cells (2026)
- 1R01DK148614-01: Engineering synthetic suppressor cells for immune protection of transplanted islet beta cells (2026)
- 5R01CA258789-05: Ameliorating off-target toxicities of CAR T cells by engineering NOT gates (2026)
- 5R01CA249018-05: Recognizing the tumor ecosystem: Integrating stromal and cancer antigen signals to achieve precision recognition of solid tumors by CAR T cells (2025)
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