Every day we face countless pathogens that our immune system deals with successfully. In some cases, however, our immunity may be overwhelmed, and ensuing infections require therapeutic intervention. Roughly 15% of all hospital admissions in the U.S. are due to or complicated by infection, with a third of them presenting with systemic dissemination of pathogens promoting sepsis. Sepsis predominantly associates with worse outcomes, prolonged hospitalization, post-infectious sequelae, and increased morbidity and mortality even after discharge. Our group investigates the molecular mechanisms underpinning the immune dysregulation in bacterial sepsis. We study how bacteria, or purified bacterial components, are recognized and activate immune effectors, such as primary human innate cells and humoral proteolytic cascades. Currently, we focus on how peptidoglycan, the “hard shell” of the bacterial cell wall, disrupts immunothrombotic mechanisms designed to limit the spread of the pathogen and the implications for septic pathology. We subsequently modulate these immune networks in non-human primate models of sepsis, where we try to define new therapeutic strategies that may improve septic pathology and outcomes.
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
Popescu NI, Cochran J, Duggan E, Kluza J, Silasi R, Coggeshall KM. Internalization of Polymeric Bacterial Peptidoglycan Occurs through Either Actin or Dynamin Dependent Pathways. Microorganisms 10, 2022 March, PMID: 35336127, PMCID: PMC8951193
Keshari RS, Popescu NI, Silasi R, Regmi G, Lupu C, Simmons JH, Ricardo A, Coggeshall KM, Lupu F. Complement C5 inhibition protects against hemolytic anemia and acute kidney injury in anthrax peptidoglycan-induced sepsis in baboons. Proc Natl Acad Sci U S A 118, 2021 September, PMID: 34507997, PMCID: PMC8449412
Popescu NI, Girton A, Burgett T, Lovelady K, Coggeshall KM. Monocyte procoagulant responses to anthrax peptidoglycan are reinforced by proinflammatory cytokine signaling. Blood Adv. 2019 Aug 27;3(16):2436-2447. doi: 10.1182/bloodadvances.2019000513. PMID: 31416821; PMCID: PMC6712522.
Popescu NI, Silasi R, Keshari RS, Girton A, Burgett T, Zeerleder SS, Gailani D, Gruber A, Lupu F, Coggeshall KM. Peptidoglycan induces disseminated intravascular coagulation in baboons through activation of both coagulation pathways. Blood. 2018 Aug 23;132(8):849-860. doi: 10.1182/blood-2017-10-813618. Epub 2018 Jun 19. PMID: 29921614; PMCID: PMC6107880.
Girton AW, Popescu NI, Keshari RS, Burgett T, Lupu F, Coggeshall KM. Serum Amyloid P and IgG Exhibit Differential Capabilities in the Activation of the Innate Immune System in Response to Bacillus anthracis Peptidoglycan. Infect Immun. 2018 Apr 23;86(5):e00076-18. doi: 10.1128/IAI.00076-18. PMID: 29531132; PMCID: PMC5913848.
Keshari RS, Silasi R, Popescu NI, Patel MM, Chaaban H, Lupu C, Coggeshall KM, Mollnes TE, DeMarco SJ, Lupu F. Inhibition of complement C5 protects against organ failure and reduces mortality in a baboon model of Escherichia coli Proc Natl Acad Sci U S A. 2017 Aug 1;114(31):E6390-E6399. doi: 10.1073/pnas.1706818114. Epub 2017 Jul 18. PMID: 28720697; PMCID: PMC5547645.
Wolf AJ, Reyes CN, Liang W, Becker C, Shimada K, Wheeler ML, Cho HC, Popescu NI, Coggeshall KM, Arditi M, Underhill DM. Hexokinase Is an Innate Immune Receptor for the Detection of Bacterial Peptidoglycan. Cell. 2016 Jul 28;166(3):624-636. doi: 10.1016/j.cell.2016.05.076. Epub 2016 Jun 30. PMID: 27374331; PMCID: PMC5534359.
Arthritis & Clinical Immunology Research Program, MS 29
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104