Professional Education


  • Doctor of Philosophy, University of Colorado, Cell and Developmental Biology (2022)
  • Bachelors of Science, North Carolina State University, Polymer Chemistry (2016)
  • Bachelors of Science, North Carolina State University, Molecular and Structural Biochemistry (2016)
  • Bachelors of Science, North Carolina State University, Biological Sciences (2016)

Stanford Advisors


All Publications


  • Interleukin-6-dependent epithelial fluidization initiates fibrotic lung remodeling. Science translational medicine Stancil, I. T., Michalski, J. E., Hennessy, C. E., Hatakka, K. L., Yang, I. V., Kurche, J. S., Rincon, M., Schwartz, D. A. 2022; 14 (654): eabo5254

    Abstract

    Chronic disease results from the failure of tissues to maintain homeostasis. In the lung, coordinated repair of the epithelium is essential for preserving homeostasis. In animal models and human lung disease, airway epithelial cells mobilize in response to lung injury, resulting in the formation of airway-like cysts with persistent loss of functional cell types and parenchymal architecture. Using live-cell imaging of human lung epithelial cultures and mouse precision-cut lung slices, we demonstrated that distal airway epithelia are aberrantly fluidized both after injury and in fibrotic lung disease. Through transcriptomic profiling and pharmacologic stimulation of epithelial cultures, we identified interleukin-6 (IL-6) signaling as a driver of tissue fluidization. This signaling cascade occurred independently of canonical Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling but instead was dependent on a downstream SRC family kinase (SFK)-yes-associated protein (YAP) axis. Airway epithelial-fibroblast cocultures revealed that the fibrotic mesenchyme acts as a source of IL-6 family cytokines, which drive airway fluidization. Inhibition of the IL-6-SFK-YAP cascade was sufficient to prevent fluidization in both in vitro and ex vivo models. Last, we demonstrated a reduction in fibrotic lung remodeling in mice through genetic or pharmacologic targeting of IL-6-related signaling. Together, our findings illustrate the critical role of airway epithelial fluidization in coordinating the balance between homeostatic lung repair and fibrotic airspace remodeling.

    View details for DOI 10.1126/scitranslmed.abo5254

    View details for PubMedID 35857823

  • Aberrant Multiciliogenesis in Idiopathic Pulmonary Fibrosis. American journal of respiratory cell and molecular biology Kim, E., Mathai, S. K., Stancil, I. T., Ma, X., Hernandez-Gutierrez, A., Becerra, J. N., Marrero-Torres, E., Hennessy, C. E., Hatakka, K., Wartchow, E. P., Estrella, A., Huber, J. P., Cardwell, J. H., Burnham, E. L., Zhang, Y., Evans, C. M., Vladar, E. K., Schwartz, D. A., Dobrinskikh, E., Yang, I. V. 2022

    Abstract

    We previously identified a novel molecular subtype of idiopathic pulmonary fibrosis (IPF) defined by increased expression of cilium-associated genes, airway mucin gene MUC5B, and KRT5 marker of basal cell airway progenitors. Here we show the association of MUC5B and cilia gene expression in human IPF airway epithelial cells, providing further rationale for examining the role of cilium genes in pathogenesis of IPF. We demonstrate increased multiciliogenesis and changes in motile cilia structure of multiciliated cells both in IPF and bleomycin lung fibrosis model. Importantly, conditional deletion of a cilium gene, Intraflagellar Transport 88 (Ift88), in Krt5 basal cells reduces Krt5 pod formation and lung fibrosis whereas no changes are observed in Ift88 conditional deletion in club cell progenitors. Our findings indicate that aberrant injury-activated primary ciliogenesis and Hedgehog signaling may play a causative role in Krt5 pod formation, which leads to aberrant multiciliogenesis and lung fibrosis. This implies that modulating cilium gene expression in Krt5 cell progenitors is a potential therapeutic target for IPF.

    View details for DOI 10.1165/rcmb.2021-0554OC

    View details for PubMedID 35608953

  • An Airway-Centric View of Idiopathic Pulmonary Fibrosis. American journal of respiratory and critical care medicine Stancil, I. T., Michalski, J. E., Schwartz, D. A. 2022

    Abstract

    Idiopathic pulmonary fibrosis (IPF) is the cumulative manifestation of countless, spatially and temporally distinct, microscopic foci of maladaptive repair in response to recurrent lung injury. However, the key drivers, essential cells, and critical mechanisms of maladaptive repair in IPF remain elusive. Decades of research have focused on alveolar injury and alveolar-mesenchymal crosstalk with their association to type II alveolar epithelial defects, fibroblast activation, and progressive lung fibrosis resulting in diminished organ function. Additionally, it has been well documented that immune and endothelial cell-types are involved in IPF. However, the airway epithelium has been incompletely described in IPF, even with significant evidence of airway-specific involvement. One of the first descriptions of distal airway dysfunction in IPF was over four-decades ago; however, since this discovery, our understanding of distal airway epithelial contributions to IPF pathogenesis has not kept pace with other tissues-types or anatomical regions of the lung. Healthy distal, which is defined here as an airway < 2 mm in internal diameter, airway epithelium is composed primarily of progenitor, mucus-producing, and multiciliated cell populations. Large increases in progenitor population diversity, misexpression of mucus, and possible aberrant ciliation observed in IPF has reinvigorated interest in the distal airway epithelium.

    View details for DOI 10.1164/rccm.202109-2219PP

    View details for PubMedID 35446237

  • Integrin Axis Regulates Airway Biophysical Dysfunction in Idiopathic Pulmonary Fibrosis. American journal of respiratory cell and molecular biology Stancil, I. T., Michalski, J. E., Schwartz, D. A. 2022; 66 (2): 235-237

    View details for DOI 10.1165/rcmb.2021-0224LE

    View details for PubMedID 35103555

    View details for PubMedCentralID PMC8845129

  • Pulmonary fibrosis distal airway epithelia are dynamically and structurally dysfunctional. Nature communications Stancil, I. T., Michalski, J. E., Davis-Hall, D., Chu, H. W., Park, J. A., Magin, C. M., Yang, I. V., Smith, B. J., Dobrinskikh, E., Schwartz, D. A. 2021; 12 (1): 4566

    Abstract

    The airway epithelium serves as the interface between the host and external environment. In many chronic lung diseases, the airway is the site of substantial remodeling after injury. While, idiopathic pulmonary fibrosis (IPF) has traditionally been considered a disease of the alveolus and lung matrix, the dominant environmental (cigarette smoking) and genetic (gain of function MUC5B promoter variant) risk factor primarily affect the distal airway epithelium. Moreover, airway-specific pathogenic features of IPF include bronchiolization of the distal airspace with abnormal airway cell-types and honeycomb cystic terminal airway-like structures with concurrent loss of terminal bronchioles in regions of minimal fibrosis. However, the pathogenic role of the airway epithelium in IPF is unknown. Combining biophysical, genetic, and signaling analyses of primary airway epithelial cells, we demonstrate that healthy and IPF airway epithelia are biophysically distinct, identifying pathologic activation of the ERBB-YAP axis as a specific and modifiable driver of prolongation of the unjammed-to-jammed transition in IPF epithelia. Furthermore, we demonstrate that this biophysical state and signaling axis correlates with epithelial-driven activation of the underlying mesenchyme. Our data illustrate the active mechanisms regulating airway epithelial-driven fibrosis and identify targets to modulate disease progression.

    View details for DOI 10.1038/s41467-021-24853-8

    View details for PubMedID 34315881

    View details for PubMedCentralID PMC8316442

  • In primary airway epithelial cells, the unjamming transition is distinct from the epithelial-to-mesenchymal transition. Nature communications Mitchel, J. A., Das, A., O'Sullivan, M. J., Stancil, I. T., DeCamp, S. J., Koehler, S., Ocaña, O. H., Butler, J. P., Fredberg, J. J., Nieto, M. A., Bi, D., Park, J. A. 2020; 11 (1): 5053

    Abstract

    The epithelial-to-mesenchymal transition (EMT) and the unjamming transition (UJT) each comprises a gateway to cellular migration, plasticity and remodeling, but the extent to which these core programs are distinct, overlapping, or identical has remained undefined. Here, we triggered partial EMT (pEMT) or UJT in differentiated primary human bronchial epithelial cells. After triggering UJT, cell-cell junctions, apico-basal polarity, and barrier function remain intact, cells elongate and align into cooperative migratory packs, and mesenchymal markers of EMT remain unapparent. After triggering pEMT these and other metrics of UJT versus pEMT diverge. A computational model attributes effects of pEMT mainly to diminished junctional tension but attributes those of UJT mainly to augmented cellular propulsion. Through the actions of UJT and pEMT working independently, sequentially, or interactively, those tissues that are subject to development, injury, or disease become endowed with rich mechanisms for cellular migration, plasticity, self-repair, and regeneration.

    View details for DOI 10.1038/s41467-020-18841-7

    View details for PubMedID 33028821

    View details for PubMedCentralID PMC7542457