Department of Medicine

Department of Medicine

  Division of Pulmonary, Allergy and Critical Care Medicine

Faculty Profile: YUTONG ZHAO, MD, PhD


Dr. Yutong Zhao's Research

Dr. Zhao’s laboratory focuses on role of lysophospholipids in pulmonary epithelial and endothelial inflammation and remodeling. Two lysophospholipids, lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) have been known to regulate cellular responses through ligation to specific G-protein-coupled receptors. LPA and S1P levels were detectable in plasma and BAL fluids in both physiological and pathological conditions. Pulmonary epithelial and endothelial cells express their receptors on cell surface. Current research works in Dr. Zhao’s laboratory is investigating the role of LPA in pulmonary epithelial cells-mediated inflammation and barrier function and remodeling. Dr. Zhao is also interesting in role of ubiquitin-proteasome system in regulation of lung inflammation and injury, especially the F-box proteins in signal transduction in lung epithelium.

1) LPA regulates pulmonary epithelial barrier integrity. E-cadherin is a member of the cadherin family that mediates calcium-dependent cell-cell adhesion. The regulated expression and the plasma membrane localization of E-cadherin are critical for the maintenance of epithelial cell-cell junctions crucial to the functional integrity of the epithelial barrier. Dr. Zhao and colleagues determined that LPA treatment tightened the pulmonary epithelial cell barrier. Exposure to LPA enhanced accumulation of E-cadherin and c-Met complex at cell-cell contacts through activation of PKC isoforms. E-cadherin relocalization to cell-cell contacts was critical for LPA-induced enhanced airway epithelial barrier function.

2) Autotaxin regulates pulmonary epithelial cell motility. Alveolar cell migration is a crucial step for re-epithelialization remodeling after lung injury. Dr. Zhao and colleague’s research results showed that secreted autotaxin (ATX), which exhibits lysophospholipase D (lysoPLD) activity, stimulated lung alveolar cell migration through lysophosphatidic acid (LPA) generation-dependent and -independent pathways.

3) ST2 is a recently identified receptor for interleukin-33 (IL-33) that mediates pulmonary inflammation and immune-related disorders, such as asthma and rheumatoid arthritis. Currently, very little is known regarding the molecular regulation of ST2 expression. Dr. Zhao’s research group has shown that LPA increases ST2 gene expression through chromatin remodeling. Further, they showed that an orphan protein belonging to the Skp1-Cullin-F-box ubiquitin E3 ligase family, termed FBXL19, selectively binds to ST2 to mediate its polyubiquitination and elimination within the proteasome. ST2 degradation involves ST2 phosphorylation by glycogen synthase kinase 3β. Over-expression of FBXL19 abrogates pro-apoptotic and inflammatory effects of IL-33 and lessens the severity of lung injury in murine pneumonia models. These results suggest that modulation of the IL-33-ST2L axis by ubiquitin ligases might serve as a unique strategy to lessen pulmonary inflammation.