A research project co-led by James Hagood, MD, professor of pediatrics at the UNC School of Medicine, and colleagues will be supported in creating an atlas of the cells and cellular interactions in the nasal and oral cavities, throat, and lower airways of pediatric populations in unprecedented detail.

 

Digital maps of upper and lower airway cells revealing specific cell types and their precise functions and locations within healthy tissues. Credit: AstroSuite analysis package: Kevin M. Byrd, Bruno Matuck, Quinn Easter, Khoa Huynh, Jinze Liu (VCU).

Scale Biosciences announced the winning projects of the 100 Million Cell Challenge, a research initiative that aims “to push the boundaries of single cell genomics research by encouraging large-scale projects across diverse biological systems.” The projects were selected based on their ability to address critical challenges in global health through global health equity, disease characterization, cancer biology, or therapeutic intervention.

A diverse and collaborative team of researchers from the UNC Children’s Research Institute and the Marsico Lung Institute at the UNC School of Medicine, along with global colleagues, will lead one of 14 winning projects from the challenge.

The projecttitled “Mapping the Pediatric Inhalation Interface: Nose, Mouth, and Airways” will receive financial support to map 2 to 4 million cells in the childhood respiratory system in unprecedented detail, allowing researchers to better understand respiratory diseases and conditions in pediatric populations — from asthma to viral infections and allergies. The new research will be fully funded and supported by Scale Biosciences, the Chan Zuckerberg Initiative (CZI), Ultima, Nvidia, and BioTuring.

In the wake of SARS-CoV-2, respiratory syncytial virus (RSV), and walking pneumonia surges, it has become glaringly apparent how often children are exposed to respiratory diseases. However, little research has been done to understand what is happening the precise moment and at the precise locations where the body comes in contact with airborne pathogens, allergens, and pollutants. This location is termed the pediatric inhalation interface.

James S. Hagood, MD
James S. Hagood, MD

The research team, co-led by James S. Hagood, MD, professor of pediatrics and director of the Program for Rare and Interstitial Lung Disease at the Children’s Research Institute and Marsico Lung Institute, and Kevin M. Byrd, DDS, PhD, adjunct assistant professor at the UNC Adams School of Dentistry, will be creating an “atlas” of healthy tissues and fluids from the respiratory systems of pediatric subjects from birth through pre-adolescence to address this critical gap in knowledge.

Other UNC School of Medicine researchers involved in the project include Richard Boucher, MD, the James C. Moeser Eminent Distinguished Professor of Medicine; Michelle Hernandez, MD, professor of pediatrics; Adam Kimple, MD, PhD, associate professor of otolaryngology/head & neck surgery; and Scott Randell, PhD, professor of cell biology and physiology and professor of medicine.

Much like a city blueprint, the atlas will map out the cells that make up the mucosal surfaces of the nasal and oral cavities, throat, and lower airways in detail. The atlas can also outline how these mucosal cells interact with one another when the body is healthy. Using artificial intelligence, researchers will visualize their data in 3D and create a realistic model of the body.

“These digital maps are transformed into vibrant, color-coded landscapes and cells and interaction networks, showcasing how cells collaborate to support essential functions like breathing, chewing, and speaking, while uncovering potential biomarkers for further research,” said Byrd.

Kevin M. Byrd, DDS, PhD
Kevin M. Byrd, DDS, PhD

Understanding the cellular makeup and development of the inhalation interface in children will help researchers better understand the early immune responses and particular cellular mechanisms that may increase a child’s vulnerability to respiratory conditions or even shield them from such diseases.

The open access atlas will ultimately serve as a foundational reference other researchers can use to study respiratory disease mechanisms in diverse pediatric populations, which could lead to improved diagnostics, preventive strategies, and targeted therapies tailored to pediatric needs.

The research team plans to engage with local and global communities to improve their shared understanding of the pediatric inhalation interface and expand future disease-oriented research to address global pediatric health needs.

Other partners on this project include researchers from Duke University, Virginia Commonwealth University, the Institute for Stem Cell Science and Regenerative Medicine (inStem) in Bangalore India, Pontifical University of Rio Grande do Sul, University of Sao Paulo, and Helmholtz Zentrum München Germany.