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Children's National Researchers Uncover Therapeutic Target Linked to Sepsis

Washington, DC -- Yang Liu, PhD, Director and Bosworth Chair of the Cancer Biology Center for Cancer and Immunology Research at Children’s National Health System, and his colleagues Pan Zheng, MD, McKnew Professor of Cancer Biology, and Guo-Yun Chen, PhD,  Assistant Professor of Immunology , have uncovered a “promising new therapeutic  target” in an experimental model of sepsis in mice that could open the door for improved treatment of inflammation linked to sepsis.

Sepsis is a complication of an infection, and can damage multiple organ systems and potentially lead to death. Early treatment of sepsis, usually with antibiotics and large amounts of intravenous fluids, improves chances for survival.

Dr. Liu and his team reported in the journal eLife a certain enzyme that moves within cells and disrupts interactions that normally serve to dampen inflammation associated with sepsis.

Receptors and protein receptors that are normally at odds interact and “act a bit like a brake” to slow down receptors. A key regulator is an enzyme called Neu1, which moves within the cells and potentially disrupts interactions that rely on sialic acid on the proteins, and triggers the immune response against the pathogens.

“Inflammation to tissue injuries is normally restrained when Neu1 stays inside the cells and exacerbated when Neu1 moves to cell surface,” says Dr. Liu. “However, when it moves to cell surface, it becomes vulnerable to inhibitors. The Neu1 enzyme may be a promising new target for treating sepsis.”

Many living things have proteins called toll-like receptors (TLRs) that detect invading bacteria, viruses, and other pathogens. Another family of proteins, Siglecs, attach themselves to other proteins and inhibits the immune response. Dr. Liu’s team found that Siglecs interact with the TLRs and slow down inflammation.

The promising target, the enzyme known as Neu1, moves to cell surface “disrupts interaction between the TLRs and the Siglecs and triggers exacerbated inflammation in cases of sepsis.  By inhibiting Neu1, Dr. Liu’s team successfully protected mice against sepsis.

Contact: Joe Cantlupe at 202-476-4500. 


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