Dr. Guoyun Chen Recieves $2.28 Million for Sepsis Treatment Research

Guoyun Chen, PhD, MD, an associate professor of Pediatrics Research at the UT Health Science Center and basic scientist at the Children's Foundation Research Institute at Le Bonheur Children's Hospital, has been awarded $2.26 million from the National Institute of Allergy and Infectious Diseases to continue researching new ways to treat sepsis, a potentially deadly immune response to infection.

In his project titled "The molecular mechanism of Siglec-E in bacterial clearance," Dr. Chen is building on prior work investigating key interactions at the molecular level that may help inhibit bacterial sepsis progression.

Most cases of septic shock are caused by a type of bacteria known as Gram-negative bacteria, the most common being E. coli. In other research, Dr. Chen and his team previously discovered that special immune system receptors called Siglecs played a key role in the progression of sepsis. They found lack of Siglec-E increased mortality in organisms infected with Gram-negative bacteria. This heightened susceptibility correlated with impaired bacterial clearance, suggesting Siglec-E helps control the immune response against Gram-negative bacteria.

In addition, infection with Gram-negative E. coli strains (25922 and DH5a) induced Siglec-E expression, leading to increased production of a key molecule, reactive oxygen species (ROS), for killing bacteria. On the other hand, infections with Gram-positive bacteria like Staphylococcus aureus or Listeria monocytogenes caused a decrease in Siglec-E, resulting in lower ROS production.

In this newly funded study, the Chen lab will now work to discover how Siglec-E helps in clearing bacterial infections. His team will investigate how Siglec-E differently regulates the immune response during infections by Gram-positive and Gram-negative bacteria, and to develop new treatment strategies for bacterial sepsis. By achieving these goals, the team hopes to uncover new ways to treat sepsis and improve outcomes for patients affected by this life-threatening condition.

"Sepsis is still one of the leading causes of death worldwide," said Dr. Chen. "Effective therapies for sepsis could help to reduce its associated mortality and improve outcomes of patients with severe sepsis."