image: Jason McCarthy, Ph.D., in the laboratory
Credit: Masonic Medical Research Institute
Utica, N.Y. – The Masonic Medical Research Institute (MMRI), in collaboration with Northwestern University, has been awarded a new grant from the National Institutes of Health (NIH) to develop innovative imaging strategies aimed at improving the diagnosis and management of antibody-mediated rejection (AMR) following lung transplantation.
AMR remains a major barrier to long-term transplant success, in part due to the complexity of the immune response and the lack of reliable, non-invasive diagnostic tools. Current approaches often rely on invasive biopsies and indirect markers that do not fully capture the dynamic nature of the rejection process.
The newly funded project will focus on developing fluorogenic imaging probes capable of detecting complement activation, a key driver of AMR, in real time. By targeting complement convertase activity, rather than downstream deposition products that can persist long after immune activation, the approach aims to provide a more precise and timely assessment of rejection.
“Antibody-mediated rejection is a highly heterogeneous process, and understanding its underlying mechanisms is critical to improving patient outcomes,” said Jason R. McCarthy, Ph.D., Associate Director of Research and Professor of Biomedical Research and Translational Medicine at MMRI. “This work seeks to provide clinicians with tools to more accurately identify and monitor rejection as it occurs, which could ultimately guide more personalized treatment strategies.”
The research builds on prior work demonstrating the utility of fluorogenic probes in tracking immune activity in preclinical models. In this study, investigators will evaluate the ability of newly developed probes to characterize different AMR endotypes in murine transplant models and assess their responsiveness to complement inhibitors targeting distinct points in the activation pathway.
To further explore clinical applicability, the team will also test the imaging approach in a novel porcine ex vivo lung perfusion system designed to model human complement activation. This dual-platform strategy is intended to accelerate translation of the technology toward use in patients.
“By combining expertise in complement biology and advanced imaging, this collaboration aims to address a critical unmet need in transplantation,” said Dr. Carl Atkinson, Ph.D., of Northwestern University.
By enabling non- or minimally invasive visualization of complement activity, the project aims to improve diagnostic precision and support the development of targeted therapies for transplant recipients.
Funding for this project was provided by the National Institutes of Health.