Dr. Zhao’s research focuses on lung epithelium biology and pathophysiology in lung inflammatory disorders. There are two research directions in his laboratory: (1) investigating the role of lysophospholipids in the regulation of lung epithelial barrier integrity, migration, and cytokine release; and (2) studying how the ubiquitin-proteasome system regulates immune-modulating protein stability in the lungs. His initial work incorporated sophisticated approaches using molecular and biochemical tools to reveal that lysophosphatidic acid (LPA) regulates lung epithelial barrier integrity and protects against endotoxin-induced lung injury. He showed that LPA induced E-cadherin accumulation at cell-cell contacts, resulting in enhancing lung epithelial barrier integrity and cell migration, therefore facilitating wound closure. His recent study has suggested that LPA receptors have proinflammatory effects in lung inflammatory disorders. Dr. Zhao has developed a new research direction related to the role of the ubiquitin-proteasome system in the regulating innate receptor stability. A landmark contribution by Dr. Zhao in this field is the discovery of an orphan ubiquitin E3 ligase component, called FBXL19, which was found to target the IL-33 receptor for its ubiquitination and degradation, thus lessening the severity of the lung injury. Dr. Zhao provided the first evidence showing that FBXL19 displays an anti-inflammatory property in lung inflammatory diseases. This seminal discovery was the first characterization of how the IL-33 receptor was controlled at the molecular level. Currently, Dr. Zhao is seeking more FBXL19 substrates and has revealed that FBXL19 also targets small G proteins, such as Rac1 and RhoA, for their ubiquitination and disposal.
Yutong Zhao, MD, PhD