We focus on the nervous system and communication between nerves and airway smooth muscles, the pulmonary neuroendocrine system, and immune cells. We believe that this communication can be harnessed to tackle airway diseases in children and to prevent disease progression into adulthood.

Summary of Our Three Main Projects

We have established a research program on the development of the nervous system in the lung. By identifying essential neurogenic factors, we hope to fully understand how damaging exposure in early life causes the rewiring of the nervous system.

Image depicting NEB innervation

Related publications:

  1. Langsdorf A, Radzikinas K, Kroten A, Jain S, Ai X. Neural crest cell origin and signals for intrinsic neurogenesis in the mammalian respiratory tract. Am J Respir Cell Mol Biol. 2011; 44: 293-301.
  2. Radzikinas K, Aven L, Jiang Z, Tran T, Paez-Cortez J, Boppidi K, Lu J, Fine A, Ai X. A Shh/miR-206/BDNF cascade coordinates innervation and formation of airway smooth muscle. J Neurosci. 2011; 31:15407-15415.
  3. Aven L, Paez-Cortez J, Achey R, Krishnan R, Ram-Mohan S, Cruikshank W, Fine A, Ai X. An NT4/TrkB dependent increase in innervation links early-life allergen exposure to persistent airway hyper-reactivity. FASEB J. 2014; 28:897-907.
  4. Patel KR, Aven L, Shao F, Krishnamoorthy N, Duvall MG, Levy BD, Ai X. Mast cell-derived neurotrophin 4 mediates allergen-induced airway hyperinnervation in early life. Mucosal Immunol. 2016; 9:1466-1476.

We are particularly interested in defining nerve-derived mechanisms that regulate airway smooth muscle contractility, neuroendocrine secretion and T helper type 2 differentiation. We believe that these mechanisms underlie the susceptibility to allergic asthma.

Dopamine image

Related publications:

  1. Barrios J, Patel KR, Aven L, Achey R, Minns MS, Lee Y, Trinkaus-Randall VE, Ai X. Early life allergen-induced mucus overproduction requires augmented neural stimulation of pulmonary neuroendocrine cell secretion. FASEB J . 2017; 31(9):4117-4128.
  2. Patel KR, Bai Y, Trieu KG, Barrios J, Ai X. Targeting acetylcholine receptor M3 prevents the progression of airway hyperreactivity in a mouse model of childhood asthma. FASEB J . 2017; 31(10):4335-4346.
  3. Barrios J, Kho AT, Aven L, Mitchel JA, Park JA, Randell SH, Miller LA, Tantisira KG, Ai X. Pulmonary neuroendocrine cells secrete γ-aminobutyric acid to induce goblet cell hyperplasia in primate models. Am J Respir Cell Mol Biol . 2019 Jun;60(6):687-694.
  4. Wang W, Cohen JA, Wallrapp A, Trieu KG, Barrios J, Shao F, Krishnamoorthy N, Kuchroo VK, Jones MR, Fine A, Bai Y, Ai X. (in press). Age-related dopaminergic innervation augments T helper 2-type allergic inflammation in the postnatal lung. Immunity.

We have pioneered a cryopreservation method for precision-cut human lung slices. This method provides an unprecedented opportunity to study airway physiology and infection in human tissue from healthy and diseased donors.

Image of human lung slice

Related publications:

  1. Bai Y, Krishnamoorthy N, Patel KR, Rosas IO, Sanderson MJ, Ai X. Cryopreserved human precision-cut lung slices as a bioassay for live tissue banking. Am J Respir Cell Mol Biol. 2016; 54:656-663.
  2. Abdulnour RE, Sham HP, Douda DN, Colas RA, Dalli J, Bai Y, Ai X, Serhan CN, Levy BD. Aspirin-triggered resolvin D1 is produced during self-resolving Escherichia coli pneumonia and regulates infiltrating macrophages for the resolution of lung inflammation. Mucosal Immunol. 2016; 9:1278-1287.

Lab Members

Xingbin Ai, PhD (xai@partners.org)
Yan Bai, MD
Carolyn Garcia, MD
Wei Wang, PhD
Jiyuan Liu, PhD
Sun Wook Kim, PhD