My focus is on understanding the hematologic dysregulation during bacterial infections, with a special interest on the interplay between inflammation, coagulation and immune processes during septic development. I have investigated molecular mechanisms behind coagulopathies associated with Gram negative sepsis in both non human primates (Silasi-Mansat et al., 2010) and murine models (Chaaban et al. 2015). Prothromboticmolecular mechanisms identified at cellular level (Popescu et al., 2010) have translated into studies of immune-induced hemostatic dysregulation in patients. Our more recent work with anthrax peptidoglycan (Sun et al., 2013) has highlighted the importance of this bacterial component during Gram-positive sepsis.
Additionally, my research analyzes the incidence and the thrombotic potential of autoantibodies to protein disulfide isomerase (PDI) in the pathology of autoimune diseases, with a special focus on systemic lupus erythematosus (SLE). Specifically I have developed analytical methods to quantify the incidence of anti-PDI autoantibodies in SLE and analyze the contributions of anti-PDI autoantibodies to thrombotic events in these patients. I have studied the mechanisms regulating the initiation of coagulation, using an in vitro endothelial cell model. During these studies I have shown that modulation of the reductase function of cell surface PDI induces the exposure anionic phospholipids on endothelial surface.
2002 – B.S. – Babes-Bolyai University, Cluj Napoca, Romania
2003 – M.S. – Babes Bolyai University, Cluj Napoca, Romania
2010 – PhD – University of Oklahoma Health Sciences Center
Joined OMRF staff in 2010
Keshari RS, Silasi R, Popescu NI, Regmi G, Chaaban H, Lambris JD, Lupu C, Mollnes TE, Lupu F. CD14 inhibition improves survival and attenuates thrombo-inflammation and cardiopulmonary dysfunction in a baboon model of Escherichia coli sepsis. J Thromb Haemost, 2020 November, PMID: 33174372
Popescu NI, Keshari RS, Cochran J, Coggeshall KM, Lupu F. C3 Opsonization of Anthrax Bacterium and Peptidoglycan Supports Recognition and Activation of Neutrophils. Microorganisms 8, 2020 July, PMID: 32668703, PMCID: PMC7409185
Keshari RS, Silasi R, Popescu NI, Georgescu C, Chaaban H, Lupu C, McCarty OJT, Esmon CT, Lupu F. Fondaparinux pentasaccharide reduces sepsis coagulopathy and promotes survival in the baboon model of E. coli sepsis. J Thromb Haemost, 2019 September, PMID: 31549765, PMCID: PMC6940562
Popescu NI, Lupu C, Lupu F (2010). Role of PDI in regulating tissue factor: FVIIa activity. Thromb Res. Apr;125 Suppl 1:S38-41. PMCID: PMC2839035
Popescu NI, Lupu C, Lupu F (2010). Extracellular protein disulfide isomerase regulates coagulation on endothelial cells through modulation of phosphatidylserine exposure. Blood 116(6):993-1001. PMCID: PMC2924232
Silasi-Mansat R, Zhu H, Popescu NI, Peer G, Sfyoera G, Magotti P, Ivanciu L, Lupu C, Mollnes TE, Taylor FB, Kinasewitz G, Lambris JD, Lupu (2010) .F. Complement inhibition decreases the procoagulant response and confers organ protection in a baboon model of E. coli sepsis. Blood 116(6):1002-10. PMCID: PMC2924221
Zhang X, Yu H, Lou JR, Zheng J, Zhu H, Popescu NI, Lupu F, Lind SE, Ding W-D (2011). MicroRNA-19 (miR-19) regulates tissue factor expression in breast cancer cells. J Biol Chem 286(2):1429-35. PMCID: PMC3020751
Lupu C, Zhu H, Popescu NI, Wren JD, Lupu F (2011). Novel protein ADTRP regulates TFPI expression and function in human endothelial cells in normal conditions and in response to androgen. Blood 118(16):4463-71. PMCID: PMC3204913
Sun DW, Popescu NI, Raisley B, Keshari RS, Dale GL, Lupu F, Coggeshall KM. (2013). Bacillus anthracis peptidoglycan activates human platelets through Fc gamma RII and complement. Blood 122 (4) 571-579. PMCID: 23733338.
Arthritis & Clinical Immunology Research Program, MS 29
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104