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Sepsis is a potentially life-threatening condition caused by the immune system’s overreaction to a bacterial infection. One in three hospital deaths in the US result from sepsis. Despite its devastating impact on the human population, Jianjin Shi points out there are no drugs that treat this disease. The reason for this, he explains, is because we don’t know enough about how pathogens activate the inflammatory response that leads to sepsis. Shi focused his research on resolving this molecular process. When he began his studies, it was already known that lipopolysaccharide (LPS), a molecule from the cell wall of bacteria, is the toxic substance that triggers sepsis. However, it was unclear how LPS was being detected and the molecular pathway it activates downstream. Previous studies suggested that LPS was sensed by Toll-like receptors (TLR4), but targeting TLR4 showed no benefit in clinical trials. Shi discovered a new pathway that senses LPS inside cells, which activates caspases-4/5 and triggers pro-inflammatory cell death. Further biochemical characterization led to the unexpected result that the caspases (caspases-4/5) themselves are the sensors of LPS. Targeting this newly discovered pathway could lead to treatments for sepsis.
Featured Research Article
Shi J, Zhao Y, Wang Y, Gao W, Ding J, Li P, Hu L, Shao F. (2014) Inflammatory caspases are innate immune receptors for intracellular LPS. Nature. 514(7521):187-92
Jianjin Shi is a graduate student from Dr. Feng Shao's lab at National Institute of Biological Science (NIBS), Beijing, China. He studies how the body recognizes and fends off invading pathogens. During his PhD training, Shi discovered the intracellular sensors (caspase-4/5 in human and caspase-11 in mouse) that recognize lipopolysaccharide (LPS), the component of the bacterial cell wall that activates sepsis. He also performed a 300,000 small molecule compound screen and identified several lead compounds that may provide new treatment for sepsis, a disease without any known treatment. His discovery of the LPS intracellular sensing pathway was recognized as Signaling Breakthroughs of 2014 by the journal Science Signaling and China's top 10 scientific breakthroughs (2014) by the Ministry of Science and Technology of China. Shi has received several awards, including Ray Wu Prize (2015) for excellence in life science research (only 10 graduate students winners in China each year) and excellent graduate student of NIBS (2014 & 2015). In his spare time, Shi enjoys hiking, horseback riding, and learning about science history.
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