Noninvasive molecular imaging of complement biomarkers in kidney disease

PROJECT SUMMARY/ABSTRACT This K99/R00 application aims to provide support for Dr. Felix Poppelaars, a talented postdoctoral fellow in the laboratory of Dr. Joshua Thurman, to conduct further research and training that will allow him to successfully transition into an independent investigator in the field of kidney immunology. As part of the K99 training plan, he

will expand his knowledge and skills in molecular imaging of complement activation needed to establish himself as a leader in translational research of complement biology in nephrology. Furthermore, he will enhance his intellectual and professional skills, gain valuable mentorship, and participate in various career development

activities, that will fast-track him to reach scientific independence. Guided by strong preliminary data, his proposed research project aims to develop an innovative medical tool for the visualization and quantification of complement deposition in the kidney, using antibody-based positron emission tomography (Immuno-PET)

imaging. Activation of the complement system results in the deposition of smaller fragments on tissue. Complement deposition is often present in the renal biopsy of patients with kidney disease, making it an attractive target-of-interest for molecular imaging. Dr. Poppelaars will first (Aim 1A) uncover the molecular footprint

associated with complement deposition in kidney disease using a multi-omics approach in mice. With training from leading experts, he will then (Aim 2A) examine the application of PET imaging of complement deposition in mice with kidney disease for disease staging and prognostication. After transitioning to a faculty position, Dr.

Poppelaars will (Aim 1B) characterize the in vivo kinetics of complement deposition during kidney disease, followed by (Aim 2B) longitudinal studies of PET imaging of complement deposition in mice with kidney disease to monitor treatment responses. Finally, he will (Aim 3) translate his findings to humans by establishing the

feasibility of ex-vivo PET imaging of complement deposition in discarded donor kidneys. Overall, the proposed research has the potential to improve the care and outcomes of patients with kidney disease, by 1.) enabling longitudinal noninvasive evaluation, 2.) tailoring treatment plans, and 3.) advancing our mechanistic

understanding of the pathophysiology of kidney disease. In addition, the proposed research will open exciting avenues for future fundable research in the field of kidney transplantation. The primary mentor, Dr. Thurman, and co-mentor, Dr. Michael Holers, are internationally recognized and NIH-funded scientists with a strong history

of successful mentoring in translational immunological research. With their guidance and the support of the advisory team members Dr. Jason Lewis, Dr. Laura Barisoni, and Carl Atkinson, as well as collaborators, Dr. Poppelaars will be able to successfully complete the proposed research and training plan and transition to an

independent, extramurally funded tenure-track position at a top-tier research institution.