Laboratory of Xingbin Ai, PhD

Overview

The Ai Laboratory is dedicated to airway diseases that affect infants and young children using experimental models in mice and patient-specific airway epithelial stem cells and human donor lung slices. Diseases that the Ai lab focuses on include childhood asthma triggered by allergen exposure and respiratory syncytial viral infection and lung defects in congenital diaphragmatic hernia. The goal of Ai lab’s research is to identify novel therapeutic targets for treatment.

Research Projects

Regulation of Lung Type II Immunity by developing nerves

Allergic asthma often initiates from allergen exposure in early childhood and progresses into adulthood. As the lung continues to develop after birth, the Ai laboratory investigates the communication between the immature lung environment and the immune system in the pathogenesis of allergic asthma. The Ai lab have identified essential signals for neurogenesis in the respiratory tract during embryonic and postnatal development. Early life environmental insults affect the levels of these neurogenic signals to induce neuroplasticity and promote type 2 inflammation. Identification of molecular mechanisms underlying the development of allergic asthma in early childhood will lead to strategies to modify the progression of asthma from childhood to adulthood.

Age-Related Severity of Infection by Respiratory Syncytial Virus (RSV)

Infants and young children are prone to severe RSV infection. To date, supportive care remains the only treatment option for infants with severe RSV bronchiolitis. Early RSV infection is also associated with increased susceptibility to airway hyperreactive diseases later on. In contrast, RSV-infected adults (younger than 65 years of age) mostly have cold-like symptoms. Recent findings from the Ai Laboratory have revealed an underappreciated role of the bronchial epithelium in determining the severity of RSV infection and inflammation with age. By elucidating how adult age mediates RSV resistance in the human bronchial epithelial barrier, the Ai Laboratory thrives to identify novel therapeutic strategies to treat severe infant RSV disease.

Lung Defects in Congenital Diaphragmic Hernia (CDH)

Lung defects in newborns suffering from CDH are the main cause of mortality and morbidity. However, how the failed diaphragm closure disrupts lung development in utero is not fully understood. In collaboration with physician scientists and surgeons at MGH and Boston Children’s Hospitical, the Ai Laboratory have utilized airway epithelial basal stem cells from tracheal aspirate (TA) samples of patients to address lung pathogenesis in CDH. Recent findings have linked impaired mechano-transduction to proinflammatory phenotypes in the airways of CDH newborns, which has translational implications.

Publications

View publications

Selected Publications

• Zhao C, Bai Y, Mou H, Lerou PH, Leung DW, Narasimhan H, Wei X, Sun J, Xu JF, Fearns R, Ai X. “An immune-poised state of human bronchial epithelial cells mediates RSV resistance in adults.” bioRxiv [Preprint]. 2026 Feb 3:2026.02.02.703395. doi: 10.64898/2026.02.02.703395. PMID: 41676739; PMCID: PMC12889730.
• Zhao C, Taliento AE, Belkin EM, Fearns R, Lerou PH, Ai X*, Bai Y*. “Infant RSV infection disrupts β2 adrenergic airway relaxation via epithelial CXCL11”. Am J Respir Crit Care Med. https://doi.org/10.1093/ajrccm/aamag087.
• Riedel J, Sturm K, Pascoe CD, Peukert N, Aubert O, Hiller GGR, Ai X, Boettcher M, Gosemann JH, Lacher M, Martinovic J, Benachi A, Wagner R. (2025). “Macrophages Are Enriched Pre- and Postnatally in Hypoplastic Lungs from Patients with Congenital Diaphragmatic Hernia”. Am J Respir Crit Care Med. 211(11):2130–2133.
• Aubert O, Miyake Y, Amonkar G, Dinwoodie OM, Varisco BM, Marotta M, Zhao C, Wagner R, Chen Y, Moscatello A, Tiozzo C, Varelas X, Lerou PH, Peiro JL, Keijzer R, Ai X. (2025). “Fetal tracheal occlusion corelates with normalized YAP expression and alveolar epithelial differentiation in CDH”. Am J Respir Cell Mol Biol. 72(6):688-697.
• Aubert O, Amonkar G, Varelas X, Tilston-Lunel A, Lerou PH, Zalieckas JM, Buchmiller TL, Varisco B, Marotta M, Peiro JL, Ai X. (2025). “YAP deficiency derived NF-kB hyperactivation to disrupt airway epithelium differentiation in CDH”. Am J Respir Cell Mol Biol. 72(1):112-115.
• Zhao C, Wang W, Bai Y, Amonkar G, Mou H, Olejnik J, Hume AJ, Mühlberger E, Fang Y, Que J, Fearns R, Lerou PH*, Ai X* (2024). “Activation of STAT3-mediated ciliated cell survival protects against severe infection by respiratory syncytial virus”. J. Clin. Invest. Nov 1;134(21):e183978.
• Wang W, Garcia C, Shao F, Cohen JA, Bai Y, Fine A, Ai X. (2023) “Lung dopaminergic nerves facilitate the establishment of TH2 resident memory cells in early life.” J Allergy Clin Immunol. 152(2):386-399.
• Wagner R, Amonkar GM, Wang W, Shui JE, Bankoti K, Tse WH, High FA, Zalieckas JM, Buchmiller TL, Zani A, Keijzer R, Donahoe PK, Lerou PH, Ai X. (2023). “A tracheal aspirate-derived airway basal cell model reveals a proinflammatory epithelial defect in congenital diaphragmatic hernia.” Am J Respir Crit Care Med. 207(9):1214-1226.
• Bai Y, Guedes A, Krishnan R, Ai X. (2022) “CD38 plays an age-related role in cholinergic deregulation of airway smooth muscle contractility.” J Allergy Clin Immunol. 149(5):1643-1654.e8.
• Wang W, Cohen JA, Wallrapp A, Trieu KG, Barrios J, Shao F, Krishnamoorthy N, Kuchroo VK, Jones MR, Fine A, Bai Y, Ai X. (2019) “Age-Related Dopaminergic Innervation Augments T Helper 2-Type Allergic Inflammation in the Postnatal Lung.” Immunity. 51(6):1102-1118.e7.
• Patel KR, Aven L, Shao F, Krishnamoorthy N, Duvall MG, Levy BD, Ai X (2016) “Mast cell-derived neurotrophin 4 mediates allergen-induced airway hyperinnervation in early life.” Mucosal Immunol. 9:1466-1476.

*co-corresponding author