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Hooven Laboratory Receives Second NIH R01 Grant for Research on Group B Streptococcus Infections in Pregnancy

December 18, 2024

UPMC Newborn Medicine Program researcher Thomas Hooven, MD, was awarded his second National Institutes of Health (NIH) R01 grant in 2024 for his ongoing research into the molecular mechanisms driving Group B Streptococcus (GBS) infections during pregnancy. Dr. Hooven is an assistant professor of Pediatrics in the Division of Newborn Medicine at the University of Pittsburgh School of Medicine and an R.K. Mellon Institute for Pediatric Research Scholar at UPMC Children’s Hospital of Pittsburgh.

Investigating a Critical Pregnancy Infection

GBS is a leading cause of pregnancy-related infections worldwide, contributing to preterm labor, stillbirth, and severe neonatal disease. Although GBS colonizes the intestines or reproductive tracts of approximately 30% of healthy adults without causing issues, it can become highly invasive during pregnancy. This bacterial invasion is linked to severe pregnancy outcomes, including preterm labor, stillbirth, and neonatal infections.

“GBS is a commensal organism in many adults, but during pregnancy, it becomes a serious infectious threat,” says Dr. Hooven. “We are working to understand why this bacterium can be harmless in some environments yet highly dangerous when it invades the amniotic fluid.”

New Grant Research Objectives

Dr. Hooven’s project, "Signal Transduction, Metabolic Shifts, and Host Interactions During Group B Streptococcus Infection," explores how changes in the bacterium’s metabolic state drive its virulence.

“Our central hypothesis is that nutrient deprivation in the amniotic environment triggers stress responses in GBS, driving the expression of virulence factors that can lead to devastating pregnancy complications,” says Dr. Hooven.

The research focuses on three areas. Dr. Hooven’s team will investigate how nutrient scarcity in the amniotic fluid prompts GBS to increase the production of harmful molecules linked to infection and inflammation. Using models of human fetal membranes, they will study how these metabolic shifts influence bacterial invasion and immune system activation. The research will also use a small animal model to evaluate how changes in GBS’s metabolic profile affect pregnancy outcomes, including preterm labor and fetal loss.

“Our research will try to uncover the molecular processes that transform GBS from a harmless colonizer into a dangerous pathogen,” says Dr. Hooven. “Understanding these processes could lead to new therapies aimed at preventing pregnancy complications caused by GBS.”

Grant Reference

Project Title: Signal Transduction, Metabolic Shifts, and Host Interactions During Group B Streptococcus Infection. NIH Project Number: R01AI177991. Principal Investigator: Thomas Hooven, MD.

More About the Hooven Laboratory

The Hooven Laboratory focuses on understanding how bacterial pathogens, particularly GBS, cause neonatal infections. The lab’s research explores bacterial-host interactions during initial colonization of the newborn intestine, mechanisms of bacterial invasion, systemic spread, and immune responses. The team applies advanced molecular techniques, including CRISPR/Cas9 gene editing, single-cell RNA sequencing, and various tissue model systems. Their ultimate goal is to identify potential therapeutic targets that could be used to develop vaccines or treatments to prevent severe neonatal infections.