MMRI and Northwestern University Receive NIH Grant to Advance Non-Invasive Detection of Lung Transplant Rejection

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 detection and management of antibody-mediated rejection (AMR) following lung transplantation.

Lung transplant rejection remains one of the biggest challenges facing long-term transplant success. Current diagnostic methods often rely on invasive biopsies and indirect markers that may not fully capture the complexity of the immune response during rejection.

The newly funded project seeks to develop fluorogenic imaging probes capable of detecting complement activation in real time. Complement activation is a key driver of antibody-mediated rejection and plays a major role in transplant injury.

Unlike traditional approaches that measure downstream immune markers that can remain present long after activation has occurred, this research focuses on detecting complement convertase activity directly. Researchers hope this strategy will provide clinicians with a more accurate and timely way to identify rejection as it happens.

“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.”

Advancing Imaging Technology for Transplant Medicine

The project builds on previous research demonstrating the effectiveness of fluorogenic probes in tracking immune activity in preclinical models.

As part of the study, investigators will evaluate newly developed probes designed to characterize different AMR endotypes in murine transplant models. Researchers will also assess how these probes respond to complement inhibitors targeting different stages of the activation pathway.

To further explore the technology’s clinical potential, the team will test the imaging approach in a novel porcine ex vivo lung perfusion system designed to model human complement activation. Using both murine and porcine models is expected to help accelerate the translation of this technology toward future patient care applications.

“By combining expertise in complement biology and advanced imaging, this collaboration aims to address a critical unmet need in transplantation,” said Carl Atkinson, Ph.D., of Northwestern University.

Improving Non-Invasive Detection of Lung Transplant Rejection

By enabling non- or minimally invasive visualization of complement activity, the project aims to improve diagnostic precision and support the development of more targeted therapies for transplant recipients.

The collaboration reflects MMRI’s continued commitment to advancing innovative biomedical research that improves patient outcomes and expands understanding of complex immune-related diseases.

Funding for this project was provided by the National Institutes of Health.