# Complement convertase imaging techniques for optimization of complement therapeutic amelioration of antibody mediated rejection

> **NIH AI R01** · NORTHWESTERN UNIVERSITY · 2026 · $3,267,712

## Abstract

PROJECT SUMMARY/ABSTRACT
Therapeutic strategies to halt antibody-mediated rejection (AMR) following lung transplantation are lacking, due
in large part to the complex pathophysiology of the immune process and the multi-faceted approach that must
be taken to establish a defined diagnosis. It is becoming increasingly clear that AMR has many endotypes, with
donor-specific antibodies mediating a host of complement dependent and independent functions. Thus, the
development of strategies to stratify patients based upon endotype has the potential to revolutionize the
treatment of AMR. Pre-clinically, fluorescence imaging has been used to investigate a wide array of diseases
and disorders. In transplantation, the focus has primarily been T cell-mediated rejection, detecting leukocyte
trafficking to the graft via phagocyte-specific approaches or fluorogenic probes for inflammatory signatures, such
as cathepsin B. In our own previous work, we developed a fluorogenic probe specific to granzyme B and reported
its utility in monitoring therapeutic intervention in a murine model of myocarditis, a surrogate for cardiac transplant
rejection. As such, there is a great unmet need to develop agents capable of non-invasively diagnosing
or monitoring AMR. To this end, we have developed novel fluorogenic probes adept at detecting complement
activation in real time, via the examination of complement convertase activity, as opposed to deposition products
such as C4d, which persist for weeks at the site of deposition and can only be confirmed by invasive biopsy
procedures. Thus, the goals of this proposal are to develop non- or minimally invasive techniques to image
ongoing complement activation in-vivo. To accomplish this, we will use murine models of transplant rejection in
concert with an assortment of complement inhibitors that act at different points in the complement activation
pathway to characterize the extent to which these probes can determine complement activation. We will
concom

## Key facts

- **NIH application ID:** 11289585
- **Project number:** 1R01AI196453-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Carl  Atkinson; JASON R. McCARTHY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** AI
- **Fiscal year:** 2026
- **Award amount:** $3,267,712
- **Award type:** 1
- **Project period:** 2026-04-01T00:00:00 → 2030-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11289585

## Citation

> US National Institutes of Health, RePORTER application 11289585, Complement convertase imaging techniques for optimization of complement therapeutic amelioration of antibody mediated rejection (1R01AI196453-01). Retrieved via AI Analytics 2026-07-01 from https://api.ai-analytics.org/grant/nih/11289585. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*