Lung transplantation remains the only life-saving treatment for patients with end-stage lung disease. Primary graft dysfunction (PGD) is a form of acute lung injury affecting approximately 30% of transplant recipients. It is also responsible for up to half the deaths within 30 days post-lung transplantation and also independently increases the risk of chronic rejection, the leading cause of death beyond the first year.  PGD is primarily driven by ischemia-reperfusion injury, during which cells get damaged and release damage-associated molecular patterns (DAMPs) that trigger and perpetuate inflammatory responses. Currently, there is no treatment for PGD except for supportive care, which still does not limit the risk of the chronic rejection. Our overall aim of is to leverage the key role that the complement system plays in linking innate with adaptive immune responses. The complement cascade is a key arm of innate immunity and is activated by ischemia-reperfusion injury. We utilize biobanked specimens obtained from human lung transplant recipients, and a mouse model of orthotopic lung transplantation as a part of a multidisciplinary research team to accomplish this objective. Our discoveries form the foundation for future research in developing novel technologies in humans to detect transplant-mediated injury and to test optimally designed, targeted therapies to reduce its incidence and severity.

Representative publications

  1. Kulkarni HS, Tsui K, Sunder S, Ganninger A, Tague LK, Witt CA, Byers DE, Trulock EP, Nava R, Puri V, Kreisel D, Mohanakumar T, Gelman AE, Hachem RR. Pseudomonas aeruginosa and acute rejection independently increase the risk of donor-specific antibodies after lung transplantation. Am J Transplant. 2020 Apr;20(4):1028-1038. doi: 10.1111/ajt.15687. Epub 2019 Dec 24. PMID: 31677358; PMCID: PMC7103544.
  2. Kulkarni HS, Ramphal K, Ma L, Brown M, Oyster M, Speckhart KN, Takahashi T, Byers DE, Porteous MK, Kalman L, Hachem RR, Rushefski M, McPhatter J, Cano M, Kreisel D, Scavuzzo M, Mittler B, Cantu E 3rd, Pilely K, Garred P, Christie JD, Atkinson JP, Gelman AE, Diamond JM. Local complement activation is associated with primary graft dysfunction after lung transplantation. JCI Insight. 2020 Sep 3;5(17):e138358. doi: 10.1172/jci.insight.138358. PMID: 32750037; PMCID: PMC7526453.
  3. Kulkarni HS, Tague LK, Calabrese DR, Liao F, Liu Z, Garnica L, Shankar N, Wu X, Kulkarni DH, Bernardt C, Byers D, Chen C, Huang HJ, Witt CA, Hachem RR, Kreisel D, Atkinson JP, Greenland JR, Gelman AE. Impaired complement regulation drives chronic lung allograft dysfunction after lung transplantation. bioRxiv [Preprint]. 2024 Nov 18:2024.11.17.623951. doi: 10.1101/2024.11.17.623951. PMID: 39605452; PMCID: PMC11601477.

Active and recently completed grants

  1. Targeting the pentraxin 3-complement axis to mitigate injury post-lung transplantation (Department of Defense)
  2. Targeting the amplification loop between mitochondria and complement activation in acute respiratory distress syndrome (ARDS) (Longer Life Foundation