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).
Ion transport and fluid homeostasis; Salt and fluid regulation in the lung and other organs related to the acute lung injury / acute respiratory syndrome (ALI/ARDS), chronic obstructive pulmonary diseases (COPD), asthma, and cystic fibrosis. Pulmonary edema and dehydration of the respiratory system are critical pathogenesis of most common life-threatening airway and lung disorders.
- Regulation of scnn1 genes in injured lungs.
- Posttranslational regulation of ENaC proteins.
- Genetic variances of scnn1 genes in pulmonary diseases.
- Physiology of scnn1 genes in nonepithelial cells.
The lining fluid over the internal surface of the airways and lungs is strictly regulated. Infection, allergy, pollution, and genetic mutations cause dry or wet lungs. The gas exchange is impaired under both dry and wet conditions. Our studies will provide molecular basis for developing novel druggable targets to balance the fluid in the lung.
Ji HL, Zhao RZ, Chen ZX, Shetty S, Idell I, Matalon S. (2012) ENaC: a novel divergent amiloride-inhibitable sodium channel. American Journal of Physiology: Lung Cell and Molecular Physiology. 303:L1013-26. PMID: 22983350.
Zhao RZ, Nie HG, Su XF, Han DY, Lee A, Huang Y, Chang Y, Matalon S, Ji HL. (2012) Characterization of a novel splice variant of δ ENaC subunit in human lungs. American Journal of Physiology: Lung Cell and Molecular Physiology. 302(12):L1262-72. PMID: 22505667.
Ji HL, Dai WP, and Zhao RZ (1988). New clinical applications of pansendine. In: Liu J. S., ed. Progresses in Clinical Pharmacology. Beijing, Xueyuan Press. pp150-153.
Ji HL, Dai WP, and Zhao RZ (1988). Advance in clinical applications of pansendine. Chinese Journal of Primary Medicine 11:35-36.
Zhao RZ (1995) Treatment of infectious diseases with Chinese herbs. Journal of Beijing University of Chinese Medicine 3:26-27.
Nie HG, Zhang W, Han DY, Li QN, Li J, Zhao RZ, Su XF, Peng JB, Ji HL. (2010) 8-pCPT-cGMP stimulates αβγ ENaC activity in oocytes as an external ligand requiring specific nucleotide moieties. American Journal of Physiology: Renal Physiology. 298:F323-34. PMID: 20007351.
Molina R, Han DY, Su XF, Zhao RZ, Zhao MM, Sharp GM, Chang YC, Ji HL. (2011) Cpt-cAMP activates human epithelial sodium channels via relieving self-inhibition. Biochimica et Biophysica Acta-Biomembrane. 1808:1818-26. PMID 21419751.
Han DY, Nie HG, Su XF, Shi XM, Shi XM, Bhattarai D, Zhao RZ, Landers K, Tang H, Zhang L, Ji HL. (2011) CPT-cGMP release self-inhibition of epithelial sodium channels. American Journal of Respiratory Molecular and Cell Biology. 45(5):1007-14. PMID: 21562313.
Hao Q, Samten B, Ji HL, Zhao RZ, Tang H. (2012) Tyrosine phosphatase PTP-MEG2 negatively regulates vascular endothelial growth factor receptor signaling and function in endothelial cells. American Journal of Physiology-Cell Physiology. 303(5): C548-53. PMID: 22763125.
Song MQ, Wang H, Song L, Tian H, Li J, Zhu Y, Li J, Wang Y, Zhao RZ, Ji HL. (2014) Ectopic TSH-secreting pituitary tumor: A new case report and review of prior cases. BMC Cancer. 14:544. PMID: 25069990.
Chen Z, Zhao RZ, Zhao M, Liang X, Bhattarai D, Dhiman R, Shetty S, Idell S, Ji HL (2014). Regulation of epithelial sodium channels in urokinase plasminogen activator deficiency. American Journal of Physiology: Lung Cellular and Molecular Physiology. 2014, 307(8):L609-17. PMID: 25172911.
Ji HL, Zhao RZ, Komissarov A, Chang YC, Matthay MA. (2015) Activation of epithelial sodium channels by urokinase: cutting edge and cleavage sites. Journal of Biological Chemistry. 290: 5241-55. PMID: 25555911.
Li XM, Wang H, Zhao RZ, Ji HL. (2015) Epithelial apicobasal polarity: a suppressor of oncogenesis. Journal of Cancer. Accepted.