He Lab

Motile cilia are chemo- and mechano-sensory organelles essential to the respiratory, nervous, and reproductive systems. Although prior research has identified components of motile cilia and studied their atomic-level structures, we still do not fully understand how motile cilia are formed and equipped with these ciliary proteins pertinent to motility in vertebrates. In our lab, we combine diverse animal models, single-molecule reconstitution assays, proteomics, tissue expansion, super-resolution microscopy, and in situ cryo-tomography to better understand the evolution, biogenesis, and diverse functions of motile cilia. 

How epithelial progenitor cells decide to undergo self-renewal and how differentiated cells decide to adopt alternative cell fate trajectories are central to development and regeneration. We are interested in determining how such cell states are regulated in response to inflammatory signals in physiological and pathological conditions. Through a combination of animal models, airway organoids, single cell-omics, live imaging of mucus transport, and super-resolution microscopy, we aim to define the cellular heterogeneity and functional plasticity of airway progenitors and determine how they contribute to the repair and regeneration of the mucosal barrier.  

Given the complexity of human physiology and anatomy, disease modeling that faithfully recapitulates clinical features of many respiratory conditions remains a challenge. To understand the molecular mechanisms for human tissue regeneration, we are developing strategies to culture human respiratory organoids, which are 3D mini organ-like cell clusters that closely resemble the architecture and physiology of the human airway. We are using state-of-the-art imaging techniques, quantitative proteomics, genome editing, as well as single cell multi-omics to establish an experimentally tractable platform that is able to accurately predict the relationship between genotype, mucociliary clearance, and clinical symptoms. By translating molecular and cellular mechanisms into clinical phenotypes, these organoids afford the opportunity to study human airway biology outside of tissue and pave the way for modeling human respiratory diseases in greater detail.