Ji, James, M.D., M.S.

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Contact: james.ji@uthct.edu

Research Interest:

Regulation of epithelial fluid transport

Grant Funding:

Regulation of lung epithelial sodium channel by cGMP. NHLBI, HL087017 (PI).

Current Projects:

• Posttranslational regulation of lung epithelial sodium channels by reactive species and cGMP.
• Contribution of mesothelial ion transport to tuberculous pleural effusion.
• Salt and fluid transport at the cellular and molecular levels in bacteria and virus-induced pulmonary edema and acute lung injuries.
• Regulation of mucus clearance in inflammatic airway associated with asthma, chronic obstructive pulmonary disease (COPD), allergy, cigarette smoke, and occupational lung diseases.

Research Overview:
Epithelial sodium channel (ENaC) plays a critical role in airway mucus clearance and alveolar fluid clearance. Dysfunctional mucus/fluid clearance has been implicated in the pathogenesis of various pulmonary diseases/syndromes, for instance, Cystic fibrosis, Pseudohypoaldosteronism type 1 (PHA-1), viral and bacterial pneumonia, influenza, occupational/environmental bronchitis, chronic obstructive pulmonary disease (COPD), and allergic respiratory disorders. ENaC as a major pathway for fluid re-absorption contributes up to 70% of lavage/fluid clearance. ENaC activity is regulated by reactive oxygen/nitrogen species, protein kinases, proteinases, hormones, and toxins. Our studies on the regulation of ENaC function in lung epithelium will provide novel information to our understanding of the pathogenesis of edematous and hypersecretive pulmonary diseases.

Selected Papers:

• Ji HL, Zhao RZ, Shetty S, Idell S, Matalon S (2012). δ ENaC: a novel divergent amiloride-inhibitable sodium channel. Am J Physiol Lung Cell Mol Physiol. 2012 Dec;303(12):L1013-26. doi: 10.1152/ajplung.00206.2012. Epub 2012 Sep 14.
• Lu J, Li C, Shi C, Balducci J, Huang H, Ji HL, Chang Y, Huang Y (2012). Identification of novel splice variants and exons of human endothelial cell-specific chemotaxic regulator (ECSCR) by bioinformatics analysis. Comput Biol Chem. 2012 Dec;41:41-50. doi: 10.1016/j.compbiolchem.2012.10.003. Epub 2012 Oct 23.
• Hao Q, Samten B, Ji HL, Zhao J, Tang H (2012). Tyrosine phosphatase PTP-MEG2 negatively regulates vascular endothelial growth factor receptor signaling and function in endothelial cells. Am J Physiol Cell Physiol. 2012 Sep 1;303(5):C548-53. doi: 10.1152/ajpcell.00415.2011. Epub 2012 Jul 3. PMID: 22763125.
• 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 Physiology. 302(12):L1262-72. PMID: 22505667.
• Wu W, Shi C, Ma F, Balducci J, Huang H, Ji HL, Chang Y, Huang Y (2012). Structural and functional characterization of two alternative splicing variants of mouse endothelial cell-specific chemotaxis regulator (ECSCR). International Journal of Molecular Science. 13:4920-4936. PMID: 22606020.
• Shetty SK, Marudamuthu AS, Abernathy D, Shetty RS, Shetty P, Fu J, Idell S, Bhandary YP, Ji HL, Liu MC, Shetty S (2012). Regulation of urokinase expression at the posttranscript level by lung epithelial cells. Biochemistry. 51(1):205-13. PMID: 22166006.
• 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 stimulates human alveolar fluid clearance by releasing external Na+ self-inhibition of ENaC. American Journal of Respiratory Molecular and Cell Biology. May 11, 2011. [Epub ahead of print] doi:10.1165/rcmb.2011-0004OC. PMID:21562313.
• Molina R, Han DY, Su XF, Zhao RR, 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 1808:1818-1826. PMID: 21419751.
• Wu Z, Sawamura T, Liu MC, Fudala R, Ji HL, Kurdowska AK, Idell S, and Fu J (2011). LOX-1 deletion improves neutrophil responses, enhances bacterial clearance and reduces lung injury in a murine polymicrobiol sepsis model. Infection and Immunity. 79(7):2865-2870. PMID: 21562313.
• Yang GZ, Nie HG, Lu L, Chen J, Lu XY, Ji HL, Li QN (2011). Estrogen regulates the expression and activity of epithelial sodium channel in mouse osteoblasts. Cellular and Molecular Biology. May 24; 57: 1480-1486. PMID: 21624334.
• Han DY, Nie HG, Gu X, Nayak RC, Su XF, Fu J, Rao V, and Ji HL (2010). K+ channel openers restore verapamil-inhibited lung fluid resolution and transepithelial ion transport systems. Respiratory Research. 11:64. PMID: 20507598.
• 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. Am J Physiol Renal Physiol. 2010 Feb;298(2):F323-34. Epub 2009 Dec 9. PMID: 20007351.
• Lazrak A, Nita I, Subramaniyam D, Wei S, Song W, Ji HL, Janciauskiene S, and Matalon S (2009). Alpha(1)-antitrypsin inhibits epithelial Na+ transport in vitro and in vivo. American Journal of Respiratory Cell and Molecular Biology. 41(3):261-70. PMID: 19131639.
• Zhang P, Liu MC, Cheng L, Liang M, Ji HL, and Fu J (2009). Blockade of LOX-1 prevents endotoxin-induced acute lung inflammation and injury in mice. 1:358-365. PMID: 20375593.
• Nie HG, Wang XS, Chen L, Li J, Nan G, Su XF, Samten B, Fang XH, Smith PR, Matalon S, Ji HL. (2009) Regulation of epithelial sodium channels by cGMP/PKGII. J Physiol. 2009 Jun 1;587(Pt 11):2663-2676. Epub 2009 Apr 9.