RESEARCH FOCUS
We are mainly focused on the molecular and cellular mechanisms controlling the proliferation and differentiation of stem cells in the esophagus and lung. We are particularly interested in how these mechanisms operate at different stages of the life, fetal, adolescent, adult, regeneration and aging. A better understanding of these mechanisms will yield important insights into clinical issues that affect millions of people worldwide. The diseases that we are currently modeling include EA/TEF, eosinophilic esophagitis, Barrett's esophagus, esophageal cancer, asthma and lung fibrosis.
EA/TEF
The birth defect esophageal atresia with/without tracheoesophageal fistula (EA/TEF) affects 1/2500 newborns. The cause of EA/TEF formation remains unknown and EA/TEF often develops with other complications and birth defects. We and others have identified several signaling pathways (BMP, SHH, WNT) and transcription factors (SOX2, NKX2.1, BARX1, FOXF1 etc) are critical for the proper development of the trachea and the esophagus. We are now using live imaging coupled with mouse genetics to address the cellular mechanisms.
Eosinophilic Esophagitis
Eosinophilic esophagitis (EoE) is an emerging allergic disease with a rapid increasing incidence in people of all ages. Basal cell hyperplasia is one of the prominent problems seen in EoE patients. Previous studies using animal models have shown that long-term inflammation with increased levels of IL-5, IL-13 and Eotaxins promotes the phenotypic changes of basal progenitor cells. However, the underlying mechanisms remain to be further determined. We begin to address this issue by examining molecular pathways that mediate the inflammatory signaling. Built on some of the findings we are also conducting compound screen to find new drugs that stop progression of the disease.
Lung regeneration, asthma and fibrosis
The interplay of the epithelium and mesenchyme is critical for the morphogenesis of the lung. We recently found that epithelial signaling proteins (e.g. Wnt) participate in pulmonary regeneration and lung disease progression. We are now investigating the underlying mechanisms using mouse genetic models and in vitro assays. Knowledge obtained from these studies will provide insights into lung regeneration, pulmonary diseases like COPD, asthma and fibrosis.