Lingyin Li

Lingyin Li
Born	1981 (age 43–44) Xi'an
Alma mater	University of Wisconsin–Madison University of Science and Technology of China
Scientific career
Institutions	Stanford University, Arc Institute
Thesis	Synthetic surfaces to control cell fate  (2010)

Lingyin Li (born 1981) is a Chinese American chemical biologist who is a professor of biochemistry at Stanford University and core investigator at Arc Institute. Her research studies the chemical biology of innate immunity to design better therapeutics. She was named one of Chemical & Engineering News Talented 12 in 2020.

Early life and education

Li was born in Xi'an. ^[1] She was awarded a position on the competitive University of Science and Technology of China undergraduate program. ^[2] She was a doctoral researcher at the University of Wisconsin–Madison, where she worked with Laura L. Kiessling. She moved to Harvard Medical School as a postdoctoral researcher in the laboratory of Tim Mitchison.

Research and career

Li uses chemical biology to understand the mechanisms that underpin immunity, which she will use to develop new therapeutic pathways and targets. The activation of immunity can provide new therapeutic strategies for vaccines, cancer and viral infection.

At Harvard, she studied the drug Vadimezan (DMXAA), an activator of the stimulator of interferon genes (STING) pathway, and uncovered that DMXAA binds mouse but not human STING. ^[2] STING responds to inflammation and activates inflammatory proteins that trigger the adaptive immune system. ^[2] The combination of the innate and adaptive immune system eliminates pathogens and is predicted to fight cancer. Li also discovered ENPP1 as the first known hydrolase of cGAMP, the natural ligand and activator of STING. ENPP1 is an extracellular enzyme, which led her to propose that cGAMP is exported for degradation and thus must play an extracellular role in cancer. ^[3]

In 2015, Li set up her own lab at Stanford University ^[4] where she pioneered the study of the paracrine role of extracellular cGAMP in innate immunity and coined the phrase immunotransmitter. Her lab identified several transporters of the immunotransmitter cGAMP including SLC19A1, ^[5] SLC46A2, ^[6] LRRC8A:C, ^[7] and SLC7A1. ^[8] While many in the field have pursued STING agonists as a strategy for cancer immunotherapy, Li proposed an alternative strategy to sustain extracellular cancer signaling through the inhibition of the cGAMP hydrolases ENPP1 and ENPP3. ^{[9] [10]} She founded Angarus Therapeutics to develop ENPP1 inhibitors, which are now being tested in clinical trials.

In 2022, Li became one of the first core investigators at the Arc Institute, a nonprofit research organization that operates in partnership with Stanford University, UCSF, and UC Berkeley.

Awards and honors

• 2017 National Institutes of Health New Innovator Award ^[11]
• 2017 Ono Pharma Foundation Awardee ^[12]
• 2020 C&EN's Talented Twelve ^[2]
• 2022 Eli Lilly Award in Biological Chemistry ^[13]

Selected publications

• Lingyin Li; Qian Yin; Pia Kuss; Zoltan Maliga; José L Millán; Hao Wu; Timothy J Mitchison (26 October 2014). "Hydrolysis of 2'3'-cGAMP by ENPP1 and design of nonhydrolyzable analogs". Nature Chemical Biology . 10 (12): 1043–1048. doi:10.1038/NCHEMBIO.1661. ISSN   1552-4450. PMC   4232468 . PMID   25344812. Wikidata   Q34514089. (erratum)
• Sabrina L Ergun; Daniel Fernandez; Thomas M Weiss; Lingyin Li (20 June 2019). "STING Polymer Structure Reveals Mechanisms for Activation, Hyperactivation, and Inhibition". Cell . 178 (2): 290-301.e10. doi:10.1016/J.CELL.2019.05.036. ISSN   0092-8674. PMID   31230712. Wikidata   Q92967166.
• Carozza, J. A., Böhnert, V., Nguyen, K. C., Skariah, G., Shaw, K. E., Brown, J. A., Rafat, M., von Eyben, R., Graves, E. E., Glenn, J. S., Smith, M., & Li, L. (2020). Extracellular cGAMP is a cancer cell-produced immunotransmitter involved in radiation-induced anti-cancer immunity Nature cancer, 1(2), 184–196.
• Mardjuki, R., Wang, S., Carozza, J., Zirak, B., Subramanyam, V., Abhiraman, G., Lyu, X., Goodarzi, H., & Li, L. (2024). Identification of the extracellular membrane protein ENPP3 as a major cGAMP hydrolase and innate immune checkpoint Cell reports, 43(5), 114209.
• Merad, M., Posey, A. D., Jr, Olivero, O., Singh, P. K., Mouneimne, G., Li, L., Wallace, L. M., & Hayes, T. K. (2020). Diversity Is a Strength of Cancer Research in the U.S. Cancer cell, 38(3), 297–300.
• Cao, X., Cordova, A. F., & Li, L. (2022). Therapeutic Interventions Targeting Innate Immune Receptors: A Balancing Act Chemical reviews, 122(3), 3414–3458.

References

1. "C&EN's Talented 12: Lingyin Li". Chemical & Engineering News. Retrieved 2024-01-20.
2. "C&EN's Talented 12". Chemical & Engineering News. Retrieved 2024-01-20.
3. Li, Lingyin; Yin, Qian; Kuss, Pia; Maliga, Zoltan; Millán, José L; Wu, Hao; Mitchison, Timothy J (December 2014). "Hydrolysis of 2′3′-cGAMP by ENPP1 and design of nonhydrolyzable analogs". Nature Chemical Biology. 10 (12): 1043–1048. doi:10.1038/nchembio.1661. ISSN   1552-4450. PMC   4232468 . PMID   25344812.
4. "Lingyin Li's Profile | Stanford Profiles". profiles.stanford.edu. Retrieved 2024-01-20.
5. Ritchie, Christopher; Cordova, Anthony F.; Hess, Gaelen T.; Bassik, Michael C.; Li, Lingyin (2019-07-25). "SLC19A1 Is an Importer of the Immunotransmitter cGAMP". Molecular Cell. 75 (2): 372–381.e5. doi:10.1016/j.molcel.2019.05.006. ISSN   1097-4164. PMC   6711396 . PMID   31126740.
6. Cordova, Anthony F.; Ritchie, Christopher; Böhnert, Volker; Li, Lingyin (2021-06-23). "Human SLC46A2 Is the Dominant cGAMP Importer in Extracellular cGAMP-Sensing Macrophages and Monocytes". ACS Central Science. 7 (6): 1073–1088. doi:10.1021/acscentsci.1c00440. ISSN   2374-7943. PMC   8228594 . PMID   34235268.
7. Lahey, Lauren J.; Mardjuki, Rachel E.; Wen, Xianlan; Hess, Gaelen T.; Ritchie, Christopher; Carozza, Jacqueline A.; Böhnert, Volker; Maduke, Merritt; Bassik, Michael C.; Li, Lingyin (2020-11-19). "LRRC8A:C/E Heteromeric Channels Are Ubiquitous Transporters of cGAMP". Molecular Cell. 80 (4): 578–591.e5. doi: 10.1016/j.molcel.2020.10.021 . ISSN   1097-4164. PMID   33171122.
8. Sudaryo, Valentino; Carvalho, Dayanne R.; Lee, J. Michelle; Carozza, Jacqueline A.; Cao, Xujun; Cordova, Anthony F.; Li, Lingyin (2024-09-24). "Toxicity of extracellular cGAMP and its analogs to T cells is due to SLC7A1-mediated import". BioRxiv: The Preprint Server for Biology: 2024.09.21.614248. doi:10.1101/2024.09.21.614248. ISSN   2692-8205. PMC   11463533 . PMID   39386698.
9. Li, Lingyin (2024-05-16). "Stimulating STING for cancer therapy: Taking the extracellular route". Cell Chemical Biology. 31 (5): 851–861. doi: 10.1016/j.chembiol.2024.04.004 . ISSN   2451-9448. PMID   38723635.
10. Carozza, Jacqueline A.; Brown, Jenifer A.; Böhnert, Volker; Fernandez, Daniel; AlSaif, Yasmeen; Mardjuki, Rachel E.; Smith, Mark; Li, Lingyin (2020-11-19). "Structure-Aided Development of Small-Molecule Inhibitors of ENPP1, the Extracellular Phosphodiesterase of the Immunotransmitter cGAMP". Cell Chemical Biology. 27 (11): 1347–1358.e5. doi:10.1016/j.chembiol.2020.07.007. ISSN   2451-9448. PMC   7680421 . PMID   32726585.
11. "NIH Director's New Innovator Award Program - 2017 Award Recipients | NIH Common Fund". commonfund.nih.gov. Archived from the original on April 17, 2019. Retrieved 2024-01-20.
12. "Awardees List". www.onofound.org. Retrieved 2024-10-25.
13. "Eli Lilly Award in Biological Chemistry". Division of Biological Chemistry. Retrieved 2024-01-20.