Severe pneumonia is characterized by an increased bacterial burden, exaggerated host immune response, and cellular damage in the lungs, and is a leading cause of death worldwide. There is an urgent need to better understand host defense mechanisms in the lung, with the goal of yielding new therapies to improve pneumonia treatment. Work done in our laboratory directly addresses this need by investigating and employing locally produced complement proteins, that are an important part of the host immune response for killing pathogenic bacteria, to reduce the morbidity and mortality associated with pneumonia by leveraging its ability to protect the lung.

We have been able to develop and optimize assays to investigate complement activation in the lungs. In this context, we have also been able to show that increased complement activation is a distinctive feature of severe SARS-CoV-2 infection. Our work has formed the basis of both designing and interpreting the results of phase 3 clinical trials during the COVID-19 pandemic. Thus, we are driven to understand how the early host immune response modulates tissue damage, with the goal of designing and implementing urgently needed, novel host-focused therapies for pneumonia.

Representative publications

  1. Ma L, Sahu SK, Cano M, Kuppuswamy V, Bajwa J, McPhatter J, Pine A, Meizlish ML, Goshua G, Chang CH, Zhang H, Price C, Bahel P, Rinder H, Lei T, Day A, Reynolds D, Wu X, Schriefer R, Rauseo AM, Goss CW, O’Halloran JA, Presti RM, Kim AH, Gelman AE, Dela Cruz CS, Lee AI, Mudd PA, Chun HJ, Atkinson JP, Kulkarni HS. Increased complement activation is a distinctive feature of severe SARS-CoV-2 infection. Sci Immunol. 2021 May 13;6(59):eabh2259. doi: 10.1126/sciimmunol.abh2259. PMID: 34446527; PMCID: PMC8158979.
  2. Sahu SK, Ozantürk AN, Kulkarni DH, Ma L, Barve RA, Dannull L, Lu A, Starick M, McPhatter J, Garnica L, Sanfillipo-Burchman M, Kunen J, Wu X, Gelman AE, Brody SL, Atkinson JP, Kulkarni HS. Lung epithelial cell-derived C3 protects against pneumonia-induced lung injury. Sci Immunol. 2023 Feb 3;8(80):eabp9547. doi: 10.1126/sciimmunol.abp9547. Epub 2023 Feb 3. PMID: 36735773; PMCID: PMC10023170.
  3. Annane D, Pittock SJ, Kulkarni HS, Pickering BW, Khoshnevis MR, Siegel JL, Powell CA, Castro P, Fujii T, Dunn D, Smith K, Mitter S, Kazani S, Kulasekararaj A. Intravenous ravulizumab in mechanically ventilated patients hospitalised with severe COVID-19: a phase 3, multicentre, open-label, randomised controlled trial. Lancet Respir Med. 2023 Dec;11(12):1051-1063. doi: 10.1016/S2213-2600(23)00082-6. Epub 2023 Mar 20. PMID: 36958364; PMCID: PMC10027334.

Active and recently completed grants

  1. C3 mitigates epithelial injury in pneumonia (K08, National Institutes of Health)
  2. A locally active complement system maintaining airway epithelial cell survival and host defense in severe pneumonia (American Lung Association)
  3. Lung-derived complement in pneumonia (R01, National Institutes of Health)