The Li Lab studies how innate immune signaling shapes cancer, autoimmunity, and inflammatory disease, with a focus on the cGAS–cGAMP–STING pathway. We discovered that cells with high metabolic demand including cancer cells actively export the second messenger cGAMP, establishing extracellular cGAMP as an immunotransmitter that enables short‑range communication between these cells and the immune system. We identified the ectoenzymes ENPP1 and 3 as the hydrolases of extracellular cGAMP and revealed ENPP1/3 as innate immune checkpoints that allow cancers to erase this danger signal and evade immune surveillance. Building on this mechanistic framework, we develop small‑molecule ENPP1 inhibitors and STING modulators to reprogram tumor–immune interactions, and we apply chemical biology, structural biology, and in vivo cancer and inflammation models to translate basic signaling principles into new therapeutic strategies.
The innate immune STING pathway senses cytosolic dsDNA and generates the second messenger cGAMP, which activates STING to initiate downstream immune signaling. It exists in a delicate balance: it must detect and defend against viruses and cancer but not aberrantly respond to benign self dsDNA. We previously discovered that cGAMP is an immunotransmitter that is secreted by producing cells and detected by various immune cell types and stromal cells. We investigate cell type-specific cGAMP and STING regulation using chemical biology and genetic approaches, and discover new, potentially druggable checkpoints on the pathway.
We use classic biochemistry, structural biology, and medicinal chemistry to investigate at the atomic level how protein and small molecule immunomodulators of the STING pathway function effectively and how they fall into dysregulation and cause inflammation. In parallel, we develop and refine prototype drugs that bind to targets in the STING pathway and can be used to test therapeutic hypotheses in disease models.
Valentino Sudaryo, Dayanne R. Carvalho, Jacqueline A. Carozza, Xujun Cao, Courtney Kernick, Anthony F. Cordova, J. Michelle Lee, Theodore L. Roth, Lingyin Li
Songnan Wang, Randolph M. Johnson, Jacqueline A. Carozza, Daniel Fernandez, Jan Scicinski, Neil A. Verity, Rachel Mardjuki, Xujun Cao, Yingjie Guo, Jacqueline Papkoff, Nigel Ray, Lingyin Li
Rebecca Chan, Xujun Cao, Sabrina L. Ergun, Evert Njomen, Stephen R. Lynch, Christopher Ritchie, Benjamin Cravatt, Lingyin Li
Christopher Ritchie, Lingyin Li
Rachel Mardjuki, Songnan Wang, Jacqueline Carozza, Bahar Zirak, Vishvak Subramanyam, Gita Abhiraman, Xuchao Lyu, Hani Goodarzi, Lingyin Li
Lingyin Li
Songnan Wang, Volker Böhnert, Alby J. Joseph, Valentino Sudaryo, Gemini Skariah, Jason T. Swinderman, Feiqiao B. Yu, Vishvak Subramanyam, Denise M. Wolf, Xuchao Lyu, Luke A. Gilbert, Laura J. van’t Veer, Hani Goodarzi, and Lingyin Li
Jacqueline A Carozza, Anthony F Cordova, Jenifer A Brown, Yasmeen AlSaif, Volker Böhnert, Xujun Cao, Rachel E Mardjuki, Gemini Skariah, Daniel Fernandez, Lingyin Li
Anthony F Cordova, Christopher Ritchie, Volker Böhnert, Lingyin Li
Lauren J Lahey, Rachel E Mardjuki, Xianlan Wen, Gaelen T Hess, Christopher Ritchie, Jacqueline A Carozza, Volker Böhnert, Merritt Maduke, Michael C Bassik, Lingyin Li
Jacqueline A Carozza, Jenifer A Brown, Volker Böhnert, Daniel Fernandez, Yasmeen AlSaif, Rachel E Mardjuki, Mark Smith, Lingyin Li
Jacqueline A Carozza, Volker Böhnert, Khanh C Nguyen, Gemini Skariah, Kelsey E Shaw, Jenifer A Brown, Marjan Rafat, Rie von Eyben, Edward E Graves, Jeffrey S Glenn, Mark Smith, Lingyin Li
Sabrina L Ergun, Daniel Fernandez, Thomas M Weiss, Lingyin Li
Christopher Ritchie, Anthony F Cordova, Gaelen T Hess, Michael C Bassik, Lingyin Li
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Lingyin Li is a Professor in the Biochemistry Department and the ChEM-H institute at Stanford. She received her Ph.D at the University of Wisconsin-Madison with Dr. Laura Kiessling and performed postdoctoral studies with Dr. Timothy Mitchison at Harvard Medical School. Building on Zhijian Chen and Glenn Barber’s discovery of the cGAS–cGAMP–STING pathway, Dr. Li’s work on extracellular cGAMP and ENPP1 as an innate checkpoint revealed the full circuit architecture of the cGAS–STING pathway in cancer and inflammation. Dr. Li is the recipient of the NIH New Innovator Award in 2017, the Ono Pharma Foundation Breakthrough Science Initiative Award in 2017, and the 2022 Eli Lilly Award in Biological Chemistry.
Before joining Li lab as lab manager/ LSRP, I was working at different Stanford labs since 2004. At Li lab I maintain all the mouse strains for different projects in the lab. Outside of the lab I enjoy spending time with family and friends.
I trained in chemistry and biochemistry, completing my PhD at Stanford with Lingyin in 2021. Now, I work on identifying druggable proteins in innate immuno-oncology and developing molecules that target them. I really enjoy backpacking in the Sierra Nevada foothills and spending time with my family.
Before joining Stanford I worked at EMBL Grenoble, France, on X-ray structural characterization of plant hormone receptors and their ligands. At Li Lab I supervise protein structural work, training students. Outside of the lab, I enjoy biking and reading books.
I have a PhD in Biochemistry from Stanford. In lieu of a traditional bio, I commissioned members of my lab space to write a descriptive haiku for me:
In my PhD
I found cGAMP transporters
I enjoy biking.
Prior to Stanford, I worked in epigenetics and organic synthesis. At Arc, I work on understanding the regulation of extracellular cGAMP. Outside of lab I enjoy swimming and music.
Prior to Stanford, I majored in Chemistry at the National University of Singapore, where I worked on the organic synthesis of carbohydrate probes and imprinted polymers. At Arc, I use tools in biochemistry, computation and cell and structural biology to study molecular mechanisms of innate immune activation. Outside of the lab I enjoy mahjong, board games and mind games, eating and running so I can keep eating.
Prior to Stanford, I did my undergrad at MIT, where I worked on a joint project between the labs of Harvey Lodish and Hidde Ploegh to engineer red blood cells and nanobodies for various therapeutic purposes. At Arc, I work on how extracellular cGAMP signals in T cells. Outside of lab I enjoy doing photography, watching basketball games and trying out different food.
Prior to Stanford, I received my B.S. in Chemistry and Biology from the Massachusetts Institute of Technology (MIT), where I worked in Prof. Laura Kiessling's lab studying structure-fuction relationships of mucins by designing mucin-mimetic polymers with antivirulence properties against cholera toxin. At Arc, I work on STING signaling and regulation in T cells. Outside of lab I enjoy going on road trips, hiking, and attempting to cook Brazilian dishes.
Prior to Stanford, I received my B.A. in Chemistry and Biological Sciences from Cornell University, where I trained in organic synthesis, catalysis, and metabolomics. At Stanford, I use chemical biology approaches to investigate innate immune signaling, with a particular interest in how cGAMP transport shapes intercellular communication. My research focuses on identifying and characterizing cGAMP transporters that regulate inflammatory responses and may serve as therapeutic targets for disease. Outside of the lab, I enjoy going to the gym, watching hockey, exploring new cafés, and wandering through grocery stores.
I have a BS focused in Pharmacy Technician from the Polytechnic Institute of Health. Today, I'm an In Vivo Technician in the Li Lab at Arc.
I earned my PhD in regenerative medicine from the Chinese Academy of Sciences, where my research focused on mitochondrial biology and its therapeutic potential in disease. At Arc, I study how tumor-intrinsic programs reshape extracellular cGAMP–STING signaling and antitumor immunity, with a particular focus on ENPP1-mediated tumor–immune communication. Outside the lab, I enjoy road trips, singing, and exploring great food.
I assist Lingyin Li with day to day administrative tasks; and work with the lab on event planning, meeting scheduling, ad-hoc projects, and more. In my free time, I love exercising, especially running and playing beach tennis during the summer and snowboarding during the winter. I also enjoy exploring new restaurants in the Bay Area over the weekends.
I completed my PhD training at Westlake University, focusing on mucosal immunology before joining Li lab. My current research explores the role of extracellular cGAMP in regulating immune cells across various mouse models. Outside of work, I enjoy crafting with natural materials like shells, stones, and tree seeds. I also enjoy going to the gym and playing badminton.
I received my PhD in Chemistry at University of Chicago. At UChicago, I worked on covalent inhibitor development with peptides, and at the same time worked on novel user-friendly assay for biomarker. At Arc, I am exploring how extracellular cGAMP regulates STING signaling and activation. Outside of the lab I enjoy exploring national parks, reading, and trying new foods.
I'm a junior studying Bioengineering at Stanford University, with a particular interest in applying bioengineering to designing and investigating novel cancer immunotherapy approaches. At Arc, I investigate pathways for cGAMP transport and their implications for cancer immunotherapy and neurodegeneration.
I am a rising junior at Stanford, studying Bioengineering and Data science. I am passionate about the field of IO and translational science. I am also on the varsity women’s squash team at Stanford and enjoy hiking, music, drinking coffee and playing random sports in my free time.
