NIH Awards $2.4 Million R01 Grant to Investigate How Maternal Viral Infections Reprogram Fetal Immune Development in a Sex-Specific Manner
Key Insights
The NIH NIAID has awarded a five-year, $2.4 million R01 grant to Dr. Jiahui Ding at Wayne State University to study how maternal viral infections during pregnancy shape lifelong immune health in offspring.
The research focuses on the placenta as a key mediator, examining how placental inflammasome activation and IL-1β (search) signaling reprogram fetal hematopoietic stem cells in a sex-dimorphic manner.
Preliminary findings indicate maternal viral infection impairs neutrophil function and increases inflammatory sensitivity predominantly in male offspring, suggesting sex-specific placental inflammatory pathways.
The National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health has awarded a five-year, $2.4 million R01 grant to Jiahui Ding, M.D., Ph.D., assistant professor of Obstetrics and Gynecology at Wayne State University School of Medicine's C.S. Mott Center for Human Growth and Development (search). The grant—her first R01 as a principal investigator—will fund research aimed at uncovering how viral infections during pregnancy reprogram the developing fetal immune system, influencing susceptibility to infectious diseases throughout life.
The project, titled "Placental Responses to Maternal Viral Infection Drive Sex-Dimorphic Offspring Immune Reprogramming," focuses on the placenta as the key mediator of maternal-fetal immune communication. While maternal viral infections during pregnancy have been associated with adverse pregnancy outcomes and long-term consequences for offspring health, scientists have not fully understood how an infection in the mother can alter fetal immune development—particularly when the fetus itself is not directly infected.
"This project addresses one of the most important unanswered questions in developmental immunology: how experiences before birth influence immune health across the lifespan," Dr. Ding said. "By understanding how maternal viral infections reprogram fetal immune development, we hope to identify new biomarkers and therapeutic strategies that can reduce susceptibility to infections and improve health outcomes for future generations."
Sex-Dimorphic Immune Reprogramming
Preliminary findings from Dr. Ding's laboratory indicate that maternal viral infection impairs neutrophil function and increases inflammatory sensitivity predominantly in male offspring, suggesting that placental inflammatory pathways operate in a sex-specific manner during fetal development. Her earlier work, including studies of Zika virus (search) infection during pregnancy, found that the placenta responds differently depending on fetal sex and that these placental responses are associated with long-lasting and sex-dimorphic differences in offspring neutrophil function.
The findings are expected to provide fundamental insights into why males and females differ in their responses to infections, vaccines, and inflammatory diseases following prenatal viral exposure. Ultimately, the research may pave the way for precision medicine approaches that take into account fetal sex when developing preventive and therapeutic interventions in pregnancy.
Molecular Mechanisms and Cutting-Edge Approaches
The project will examine how placental inflammasome activation, particularly IL-1β (search) signaling, reshapes fetal hematopoietic stem cell development and establishes long-lasting immune memory. During pregnancy, the placenta acts as an important immune organ that helps educate and shape the developing fetal immune system. When a pregnant mother has an infection, the placenta senses the infection and activates immune responses.
"In this project, we will investigate how the placenta responds to maternal viral infection, how those signals affect developing fetal immune cells, and why these effects can be different between males and females. Ultimately, we hope to better understand how infections during pregnancy can influence immune health later in life and identify potential ways to protect fetal development," Dr. Ding said.
The research team will employ cutting-edge approaches including single-cell transcriptomics, epigenetic profiling, and an innovative human placenta–fetal interface organ-on-chip model to define the molecular pathways linking maternal infection to lifelong immune function.
Institutional Support and Broader Impact
"Congratulations to Dr. Jiahui Ding on earning her first NIH R01 award, an outstanding milestone for a promising early-career investigator," said School of Medicine Dean Wael Sakr, M.D. "This remarkable achievement reflects both her exceptional scientific talent and the collaborative research environment at the C.S. Mott Center. Dr. Ding's innovative research has the potential to transform our understanding of how maternal health shapes lifelong immune function and to advance precision medicine for future generations."
Gil Mor, M.D., Ph.D., the John M. Malone Jr. M.D., Endowed Chair of Women's Health and scientific director of the C.S. Mott Center, emphasized that the project complements several ongoing research programs at the center investigating how maternal infections and environmental exposures influence fetal development and the origins of disease. "A defining strength of our research environment is the integration of expertise in reproductive immunology, developmental biology, stem cell biology and systems immunology to uncover the biological basis of sexual dimorphism in disease susceptibility," Dr. Mor said. "Understanding why males and females respond differently to prenatal challenges is central to developing the next generation of precision medicine strategies for mothers and children."
Ezemenari Obasi, Ph.D., vice president for Research & Innovation at Wayne State University, added: "Dr. Ding's research has the potential to prevent lifelong health challenges in children who have been exposed to infections before birth. I look forward to the impact this research will have in our community and beyond."
The research is supported by the NIAID under award number R01AI201310. The C.S. Mott Center for Human Growth and Development (search) at Wayne State University is a nationally recognized multidisciplinary research center dedicated to advancing discoveries in reproductive biology, pregnancy, fetal development, cancer, environmental health, and the developmental origins of disease.