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NHLBI-supported project: Probing Cardiovascular Actions of GLP-1 Using Nanoparticles
In this R01 project, we aim to elucidate the molecular mechanisms of glucagon-like peptide-1 (GLP-1) in cardiovascular disease through the use of nanoparticle probes that target and image atherosclerosis. We posit that GLP-1 may directly regulate immune cell behavior by activating its receptor, GLP-1R, thereby reducing monocyte recruitment to the plaque, potentiating macrophage and cholesterol exit, and resolving inflammation. We propose to investigate locus-specific actions of GLP-1 with the use of engineered nanoparticles that will image lesional and blood leukocytes simultaneously delivering a payload of a GLP-1 mimetic within plaque.
AHA-supported project: Nanoparticle-Aided Modulation of Inflammation in Atherosclerosis
In this Scientist Development Grant we ask the following questions: 1) how can we deliver experimental agents to the sites of disease minimizing off-target side effects of therapeutic agents? 2) What are the requirements for clinical grade agents and how can we make our probes translatable? To address these questions we propose: 1) to develop highly specific, translatable mAb against Myeloid Related Protein (Mrp), which will bind to the target protein in inflammatory plaques, while minimizing off-target accumulation. 2) We will develop clinically translatable nanoparticle formulations, composed of FDA approved “Intralipid” and signaling lipids, which can exert additional effects on inflammation. We envision that strategies combining Mrp-targeted imaging probes have the potential for use in a variety of inflammatory diseases.
See our publications that resulted from this project in PubMed