Lingyin Li Lab

Proof-of-concept innate immune checkpoint inhibitor shows promise against solid tumors in rodents | Arc Institute Biochemist Lingyin Li has been pioneering a new direction for immunotherapy, searching for drugs that would turn these “cold” environments “hot”. Instead of stimulating T cells in the adaptive immune ...

Read more here: arcinstitute.org/news/stf-162...

This paper is now online at @cp-cellrepmed.bsky.social! Congratulations to all the authors. Read the paper here: www.cell.com/cell-reports...

Structural insights into STING give new ways to inhibit it Researchers have discovered a highly conserved post translational modification in the STING pathway that when inhibited stops its activity

Activation of the stimulator of interferon genes (STING) pathway can be great for fighting pathogens and treating cancer. But when the pathway is too active, it can do more harm than good, aggravating autoimmune and neurodegenerative diseases. cen.acs.org/analytical-c... #chemsky 🧪

Core Investigator @lingyinli.bsky.social's new paper in Nature Chemical Biology investigates why human STING inhibitors have shown limited efficacy, despite strong activity in mouse models.

Cysteine allostery and autoinhibition govern human STING oligomer functionality - Nature Chemical Biology Palmitoylation at C64 in stimulator of interferon genes (STING) is reported and, along with engagement of C91, is involved in dynamic cross talk with C148 to alter STING oligomer states and ultimately...

The newest paper from the lab is now out @natchembio.nature.com! A hard-won effort by Rebecca and @xujunc.bsky.social uncovers a previously undescribed post-translationally modified site that regulates STING signaling and proposes a new strategy for inhibition.

www.nature.com/articles/s41...

‘Every failed experiment is a chance to learn faster’ Stanford biochemist Lingyin Li’s lab is studying a tumor-fighting “miracle molecule” that could one day inform therapies for cancer, as well as autoimmune, neurodegenerative, and age-related diseases.

In the latest Research Matters feature, @lingyinli.bsky.social discusses her quest for more broadly efficacious cancer therapies and the importance of learning from failures.
news.stanford.edu/stories/2025...

Xujun is presenting in front of his slide on the molecular mechanism of STING signaling.

Xujun and Lingyin sharing a toast.

It's been a busy week for the Li lab! The 10th PhD in 10 years, @xujunc.bsky.social successfully defended his thesis! Congratulations, and keep an eye out for his work on new STING inhibitors and regulators!

ENPP1 inhibitor with ultralong drug-target residence time as an innate immune checkpoint blockade cancer therapy Only one in five patients is estimated to respond to immune checkpoint inhibitors, which primarily target adaptive immunity. To date, no FDA-approved immunotherapies directly activate the innate anti-...

How can we do better with cancer immunotherapy? By leveraging both adaptive and innate immunity: in our latest preprint, we and industrial partners provide the most comprehensive characterization to date of STF-1623, an inhibitor of the innate immune checkpoint ENPP1
www.biorxiv.org/content/10.1...

Lingyin and Songnan are posing for pictures beside a cake

Songnan cutting her celebratory cake

The ninth PhD defense from the lab by @songnanwang.bsky.social, now forging ahead with her MD-PhD! Excited for great things from Songnan yet to come!

New preprint: The first whole-body map of both DNA methylation and 3D genome organization at single-cell resolution across 16 human tissues, with in-depth analyses of cell type diversity of these epigenome modalities at unprecedented resolutions. (1/5)

Rebecca is standing at the lectern to the left of her presentation titled "Cysteine allostery governs STING oligomerization and function"

Rebecca walking out of her closed door session.

Rebecca Chan kicked off March for the lab by successfully defending her thesis! Watch this space for the newly minted Dr. Chan's phenomenal work on molecular mechanisms of STING signaling!

Same spot, two years apart. 🧬 Exciting to see how far we've come!

🚨 New paper alert! 🚨
Check out our latest work on HypoxyStat, a small-molecule therapy that increases oxygen-hemoglobin affinity and provides a practical form of hypoxia therapy. A great collaboration with Maze Therapeutics
🔗 Paper: doi.org/10.1016/j.ce... @cp-cell.bsky.social

Group photo of current lab members with Lingyin marked out with an arrow

We're excited to share that our fearless leader @lingyinli.bsky.social has been promoted to full Professor of Biochemistry! Here's to decades more of research in therapeutics harnessing the innate immunity!

DNA repair pathways might be important beyond maintaining genome stability. Using a CRISPRi screen, Becky Fu in the Gilbert Lab & colleagues found that the Fanconi anemia pathway is also necessary for lysosome function.

Read about the work, now on @biorxivpreprint: www.biorxiv.org/content/10.1....

Associate or Full Professor Rank Search to join the Arc Institute as a Core Investigator and the Stanford Department of Bioengineering | Arc Institute Arc Institute is a independent nonprofit research organization headquartered in Palo Alto, California.

Seeking pioneering scientists in immunology, neuroscience, and machine learning! Join Arc Institute as a Core Investigator + Stanford Bioengineering as Associate/Full Professor. Full lab funding and cutting-edge facilities in Palo Alto. Apply by Jan 15 for full consideration: shorturl.at/CuH1K

Thirteen members of the lab are posing in front of a course for golf games

Happy holidays from the Li lab!

Today we report that an engineered skin bacterium, swabbed gently on the head of a mouse, can unleash a potent antibody response against a pathogen. Could lead to topical vaccines that are applied in a cream. @djenetbousbaine.bsky.social led the charge... @natureportfolio.bsky.social 1/55

Incredible meeting #CSChemBio2024 in San Francisco including talks from @fleurmferguson.bsky.social, @danetteldaniels.bsky.social, Michelle Arkin, Ingrid Wertz, and @mishtudey.bsky.social!

Xujun is chatting with an audience member beside his poster

Rebecca is gesturing at her poster to a visitor

Graduate students Rebecca Chan and Xujun Cao (@xujunc.bsky.social) present posters on mechanistic work underlying STING activation and the development of inhibitors. Read their preprint here: www.biorxiv.org/content/10.1...

Lingyin is on stage in front of a screen presenting her slides

The Li lab is at the Cell Symposium @cellpress.bsky.social! Lab leader @lingyinli.bsky.social presents the lab's work on new therapeutic modalities harnessing the STING pathway

Patrick Hsu and Silvana Konermann

Excited that our Core investigators and Cofounders Silvana Konermann and Patrick Hsu are on this year's @vox.com #FuturePerfect50 List, highlighting also the work of @lingyinli.bsky.social, Songnan Wang, @mgdurrant.bsky.social, and Nick Perry.

www.vox.com/future-perfe...

The 2025 Bioorganic Gordon Research Conference organized by Denise Field and @doc-jlmeier.bsky.social has an amazing lineup of speakers. Sadly, I will not be able to travel, but if you are interested in #ChemicalBiology, #BioorganicChemistry or #ChemicalProteomics, make sure to check it out. (1/4)