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Wei Li, Ph.D.

Wei Li, Ph.D.

Wei Li, Ph.D.

Research Subject

Retinal Vascular Disease and Retinal Degeneration

Focus

Diabetic Retinopathy, Age-Related Macular Degeneration (AMD), Retinopathy of Prematurity

Published Articles


Roles

Research Associate Professor of Ophthalmology

Summary

The Li laboratory developed an innovative to comparative ligandomics for efficient identification of disease-associated cellular ligands. A major focus is to develop novel therapy against disease-selective angiogenic factors for diabetic macular edema, proliferative diabetic retinopathy, wet age-related macular degeneration (AMD), retinopathy of prematurity and cancer. Another focus is to investigate the role of age-related phagocytosis ligands in the dysfunction of retinal pigment epithelium and dry AMD.

Current Research

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. rdquo; 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.

Comparative ligandomics to systematically identify disease-associated endothelial ligands by in vivo binding selection
Comparative ligandomics to systematically identify disease-associated endothelial ligands by in vivo binding selection. Ligands with increased (disease-high) or decreased (disease-low) binding activity to diseased vessels can be rapidly identified. This is example to identify disease-associated ligands in experimental models with or without diabetic retinopathy (DR).

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.

Diabetes-high Scg3 induces corneal angiogenesis in diabetic but not normal experimental models
Diabetes-high Scg3 induces corneal angiogenesis in diabetic but not normal experimental models. Diabetes-low HRP-3 stimulates angiogenesis in normal but not diabetic experimental models. VEGF promotes angiogenesis in both diabetic and normal experimental models.

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.

Scg3-neutralizing polyclonal (pAb) and monoclonal antibody
Scg3-neutralizing polyclonal (pAb) and monoclonal antibody (mAb) alleviates pathological retinal neovascularization in oxygen-induced retinopathy, a surrogate animal model of retinopathy of prematurity. The pAb and mAb also restores the normal pattern of retinal vascular structure.

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.