Research Interests

Our study focuses on profiling host and microbial protein signatures in the lung to identify new endotypes, regenerative signaling pathways, biomarkers in extracellular vesicles (exosomes), and host-pathogen interaction in the specimens of septic ARDS (acute respiratory distress syndrome), COVID-19, and sarcoidosis. Technically, we apply cutting-edge scRNAseq, multi-omics, metaproteomics (microbiota), deep machine learning algorithms, 3D organoids of diseased cells and iPSC, and animal models. Mouse models of sepsis and ARDS are those infected with influenza, intratracheal instilled gastric acid, endotoxins, live bacteria, and genetically engineered humanized mouse lines. Lung edema is caused by dysfunctional salt and fluid transport. We have established a humanized SCNN1D knockin mouse line to study the role of epithelial sodium channels (ENaC) in injured lungs. To validate the results in rodents, we developed a human iPSC line with deficient SCNN1D gene. The combination of human iPSC organoids and mouse model (in vivo) will allow us to study the contribution of ENaC in the pathogenesis of lung edema and resolution. Suppressed fibrinolysis system and surfactant proteins are the pathogenic markers of lung injury, including ARDS and COVID-19. Our study demonstrates a critical role of fibrinolysis of D-dimers and lung epithelial proteins in the pathogenesis of COVID-19 and edema fluid resolution. Human iPSC lines carrying diseased mutants of sftpc and sftpb genes are combined with humanized mouse lines expressing human surfactant mutants to elucidate the intrinsic mechanisms of epithelial progenitors in fibrotic lungs.

Publications

• Ji, HL; Xi, NMS; Mohan, C; Yan, X; Jain, KG; Zang, QS; Gahtan, V; Zhao, R Biomarkers and molecular endotypes of sarcoidosis: lessons from omics and non-omics studies. Frontiers in immunology ; 14
• Li, Y; Seet, CS; Mack, R; Joshi, K; Runde, AP; Hagen, PA; Barton, K; Breslin, P; Kini, A; Ji, HL; Zhang, J Distinct roles of hematopoietic cytokines in the regulation of leukemia stem cells in murine MLL-AF9 leukemia. Stem cell reports ; 19 1
• Jain, KG; Xi, NM; Zhao, R; Ahmad, W; Ali, G; Ji, HL Alveolar Type 2 Epithelial Cell Organoids: Focus on Culture Methods. Biomedicines ; 11 11
• Zhao, R; Hadisurya, M; Ndetan, H; Xi, NM; Adduri, S; Konduru, NV; Samten, B; Tao, WA; Singh, KP; Ji, HL Regenerative Signatures in Bronchioalveolar Lavage of Acute Respiratory Distress Syndrome. bioRxiv : the preprint server for biology
• Ali, G; Zhang, M; Chang, J; Zhao, R; Jin, Y; Zhang, J; Ji, HL PAI-1 regulates AT2-mediated re-alveolarization and ion permeability. STEM CELL RESEARCH & THERAPY ; 14 1
• James (Hong-Long) Ji Bacterial Outer Membrane Vesicles Promote Lung Inflammatory Responses and Macrophage Activation via Multi-Signaling Pathways Biomedicines ; 11 568
• James (Hong-Long) Ji MetaLP: An integrative linear programming method for protein inference in metaproteomics PLoS computational biology ; 18 10 111
• James (Hong-Long) Ji Plasmin improves blood-gas barrier function in oedematous lungs by cleaving epithelial sodium channels British journal of pharmacology ; 177 13 3091-3106
• James (Hong-Long) Ji Elevated Plasmin(ogen) as a Common Risk Factor for COVID-19 Susceptibility PHYSIOLOGICAL REVIEW ; 100 3 1065-1075
• James (Hong-Long) Ji Proliferative regulation of alveolar epithelial type 2 progenitor cells by human Scnn1d gene Theranostics ; 9 26 8155-8170
• James (Hong-Long) Ji Proliferative regulation of alveolar epithelial type 2 progenitor cells by human Scnn1d gene Cell death & disease ; 7 1 e2062
• James (Hong-Long) Ji Proteolytic regulation of epithelial sodium channels by urokinase plasminogen activator: cutting edge and cleavage sites Journal of Biological Chemistry ; 290 9 5241-55
• James (Hong-Long) Ji Proteolytic regulation of epithelial sodium channels by urokinase plasminogen activator: cutting edge and cleavage sites American journal of physiology.Lung cellular and molecular physiology ; 307 8 L609-17
• James (Hong-Long) Ji 8-(4-chlorophenylthio)-guanosine-3',5'-cyclic monophosphate-Na stimulates human alveolar fluid clearance by releasing external Na+ self-inhibition of epithelial Na+ channels American Journal of Respiratory Cell & Molecular Biology ; 45 5 1007-14
• James (Hong-Long) Ji Cpt-cAMP activates human epithelial sodium channels via relieving self-inhibition Biochimica et biophysica acta ; 1808 7 1818-26
• James (Hong-Long) Ji Fibrinolytic niche is required for alveolar type 2 cell-mediated alveologenesis via a uPA-A6-CD44(+)-ENaC signal cascade SIGNAL TRANSDUCT TARGET THERE ; 6 1 97
• James (Hong-Long) Ji Prkg2 regulates alveolar type 2-mediated re-alveolarization STEM CELL RESEARCH & THERAPY ; 13 1 111