My research focuses on the molecular basis of nonvoltage-gated, amiloride-sensitive sodium channels of the ENaC/DEG family under normal and pathological conditions. I discovered that guanosine and adenosine nucleotides are able to serve as extracellular ligands to stimulate ENaC function (Nie HG, et al. AJP-Renal 2010; Han DY, et al. AJRCMB 2011; Molina R, et al. BBA 2011). In addition, my bioimmunochemical and preclinical results in knockout mice and expression cells for the first time demonstrate that uPA is a key regulator of ENaC in normal lungs by cleaving subunit gamma proteins (Zhao RZ, et al AJP-Lung 2012; Ji HL, et al. JBC 2015). Currently, the project of my group is to study a novel ENaC subunit, termed delta ENaC. My study demonstrates that this new subunit could compensate the loss of alpha ENaC to control fluid clearance in human lungs (Zhao RZ, et al. AJP-Lung 2012; Ji HL, et al. AJP-Lung 2012).