Molecular Imaging to Guide Repair and Advance Therapy: Targeting the inflammation-fibrosis axis in ischemic heart disease and remote organs

ongoing

Myocardial infarction triggers a complex interplay between inflammation and fibroblast activation, which contributes to success or failure of adequate repair. Targeted therapeutic approaches to modulate these processes have not yet been implemented clinically. The dynamic and multicellular nature of the inflammatory and fibrotic repair process in the heart is thought to be variable among individuals. Additionally, cardiac injury and treatment affect distant organs through systems-based interaction. In MIGRATe, I will explore non-invasive molecular imaging approaches to interrogate inflammatory cell populations and fibroblast activation in the heart and networking organs, for precise guidance of targeted therapeutic interventions. Imaging will delineate optimal timing and/or targeting of treatment to support endogenous healing and prevent heart failure progression. MIGRATe will also bring together imaging methods and molecular biology to decode the tissue microenvironment and identify novel biomarkers amenable to imaging and treatment. A combination of in vivo molecular imaging, single cell sorting, and transcriptome data from regions with elevated and/or suppressed imaging signal will be exploited to identify disproportionate cell subpopulations that contribute to the prognostic signal and may be targeted by therapy. Whole body imaging will simultaneously reveal the impact of cardiac cell directed therapy on the heart, alongside distant organ function, providing new insights into inter-organ communication and supporting a wholistic approach towards repair. Experimental work in mouse models will be complemented by a proof-of-concept clinical study, establishing a translational environment. Taken together, MIGRATe is designed to optimize new imaging-guided, molecular-targeted treatment strategies to improve cardiac outcome after acute myocardial infarction with corresponding benefit for reciprocal organ systems.