Wei Li, Ph.D.
Retinal Vascular Disease and Retinal Degeneration
Diabetic Retinopathy, Age-Related Macular Degeneration (AMD), Retinopathy of Prematurity
Cellular ligands are promising targets for disease therapy. For example, about 1/3 to half of marketed pharmaceuticals target human G protein-coupled receptors (GPCRs) alone. Ligands with protective roles can be overexpressed for disease therapy, and ligands with detrimental roles may be blocked to treat diseases. However, the bottleneck is how to efficiently identify ligands or receptors with pathogenic roles and therapeutic potential for different diseases.
Comparative ligandomics to systematically identify therapeutic ligands
Dr. Li developed comparative ligandomics for efficient identification of disease-associated ligands. “Disease-high” ligands with increased binding to diseased cells or organs are valuable targets for developing novel ligand-based therapies. For example, comparative ligandomics analysis in diabetic and normal experimental models successfully recently identified Scg3 as a diabetes-associated vascular permeability factor/angiogenic factor.
Scg3 as a disease selective angiogenic factor
Scg3 selectively binds to and induces angiogenesis in diabetic but not normal experimental models. In contrast VEGF binds to and stimulates angiogenesis of both diabetic and normal vessels. Scg3-like disease-high angiogenic ligands with no binding or functional activity in normal vessels are highly promising target for disease therapy but are often missed by conventional approaches because of their undetectable activity in normal conditions.
A new type of selective angiogenesis blocker for the therapy of ocular vascular diseases
We developed Scg3-neutralizing monoclonal antibody (mAb) to treat diabetic macular edema and retinopathy of prematurity (ROP). The following figure shows that anti-Scg3 mAb can alleviate the pathological retinal neovascularization and restore the vascular structure pattern in oxygen-induced retinopathy experimental models, a surrogate animal model of ROP.
RPE phagocytosis dysfunction
Another focus of the laboratory is to identify disease- or age-related phagocytosis ligands by comparative ligandomics to understand the role of retinal pigment epithelial (RPE) cell dysfunction in dry AMD. We have identified some age-related phagocytosis ligands that may contribute to the pathogenesis of dry AMD.