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Prizewinner’s Research Unveils STING as a Pivotal Immune Sensor Channel

For his work in furthering the understanding of how the human immune system senses dangerous invading pathogens, Bingxu Li has received the 2024 Michelson Philanthropies & Science Prize for Immunology.

Bingxu Liu in the lab
Bingxu Liu | Ian Haydon

Li's prize-winning essay, published in the February 16 issue of Science, investigates the role Stimulator of Interferon Genes, or STING, plays in triggering multiple distinct defenses against viruses, bacteria and tumors. It discusses how this protein orchestrates a myriad of downstream responses upon activation — resolving a significant mystery in the field of innate immunity.

"The Science editors and jury of experts were excited by the groundbreaking nature of Li's doctoral work, which reports the first known immune sensor in human cells to transport ions in response to pathogens," said Sarah Ross, associate editor at Science. "This fundamental discovery may help drive the development of next-generation vaccines and cancer immunotherapies."

The sensing and clearance of invading pathogens is crucial to the survival of living systems, ranging from bacteria to humans. This is accomplished by an intricate web of innate immune receptors or sensors that detect pathogen-specific molecules called pathogen-associated molecular patterns (PAMPS). Once activated, these receptors trigger downstream immune responses designed to defend against the invading pathogen.

However, some sensors exhibit additional behaviors upon activation. For example, activation of STING — a well-known human immune sensor — not only induces inflammation, but it also triggers various other components of the innate immune system, thus inducing multiple defenses against different types of pathogens. How STING controls these diverse downstream responses has remained unknown.

Using various genetic, biochemical and structural tools, Li and his colleagues at the Massachusetts Institute of Technology discovered that human STING plays a surprising role as an ion channel — a protein molecule that spans across a cell membrane to allow the passage of ions from one side to another. Ion channels enable cells to send and receive chemical or electrical signals.

To Li's knowledge, STING is the first ion channel that is known to sense pathogen danger in mammalian cells.

Furthermore, the discovery hints at the adaptability of innate immune proteins like STING, suggesting that they have evolved to acquire diverse new functions over time, without drastic changes.

"STING is one of the most promising targets whose activation can activate immune cells to kill cancer cells," said Li.

Although STING has any downstream effects that need to be better understood, the novel insights revealed by Li's work may one day enable use of the STING pathway as a therapeutic target.

About the Award

The Michelson Philanthropies & Science Prize for Immunology focuses on transformative research in human immunology, with trans-disease applications to accelerate vaccine and immunotherapeutic discovery. This international prize is intended to encourage and support young investigators from a wide range of disciplines, including computer science, artificial intelligence/machine learning, protein engineering, nanotechnology, genomics, parasitology and tropical medicine, neurodegenerative diseases and gene editing, who apply their expertise to perform research that has a lasting impact on vaccine and immunotherapy.

"Breakthroughs in immunology hold the potential to deliver transformative medical treatments and therapies," said Gary K. Michelson, founder and co-chair of Michelson Philanthropies. "Dr. Bingxu Liu's winning \paper and research suggest that our innate immune recognition molecules can be actively adapted, which may one day lead to treatments that help our bodies engineer better responses in immunotherapy for cancer and autoimmune diseases — two of the biggest threats to human health today. We hope his exceptional work, and that of our two finalists, Dr. Carla Nowasad and Dr. Gabriele Casirati, will generate broader support for brilliant early-career scientists who are willing to engage in high-risk, high-reward research."

2024 Finalists

headshot of Gabriele Casirati
Gabriele Casirati

Gabriele Casirati is a finalist for his essay "Stem cells in disguise: How epitope editing can empower targeted cancer immunotherapies." Casirati received his M.D. degree from the Università degli studi di Milano and Ph.D. from Università Milano-Bicocca. He is a postdoctoral research fellow at Boston Children's Hospital where his research focuses on new gene-editing approaches to enhance targeted immunotherapies for hematological malignancies.

headshot of Carla Nowosad
Carla Nowosad

Carla Nowosad is a finalist for her essay "Who goes there? How B cells assess risk in the intestine." Nowosad received undergraduate degrees from the University of Warwick and a Ph.D. from the Francis Crick Institute, National Institute for Medical Research Mill Hill. After completing her postdoctoral fellowship at Rockefeller University, Nowosad started her laboratory in the department of pathology and the Translational Immunology Center at New York University Grossman School of Medicine. Her research focuses on how B cells make decisions in the complex microenvironment of the intestine.


Walter Beckwith

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