Jie J. Zhang Laboratory

Glaucoma and intraocular pressure (IOP). Trabecular meshwork (TM) cells play a pivotal role in maintaining TM structure and regulating aqueous humor outflow. When TM cell function is compromised, structural disruptions lead to increased IOP, the primary risk factor for both primary open-angle glaucoma and steroid-induced glaucoma. Despite its significance, there remains a critical unmet need for effective, clinically viable therapies that target TM dysfunction. Their research focuses on developing transformative approaches to restore TM integrity, enhance aqueous humor drainage, and achieve sustained IOP reduction.

Wnt Signaling and Retinal Neovascularization Diseases. Proliferative retinal neovascularization is a defining feature of several major retinal diseases, including diabetic retinopathy (DR) and retinopathy of prematurity (ROP). Wnt signaling plays a pivotal role in retinal vascular development, with Dishevelled (Dvl) acting as a key regulator of neovascularization, as demonstrated in the oxygen-induced retinopathy (OIR) mouse model. His laboratory has developed a series of small-molecule Wnt inhibitors that selectively target the Dvl PDZ domain, effectively blocking oxidative stress-induced neovascularization in human retinal vascular endothelial cells. These compounds provide a robust platform for further optimization and preclinical development, offering a promising therapeutic strategy for retinal neovascularization disorders.

Small-Molecule Wnt Mimics for Corneal Limbal Stem Cell Regulation. Transplantation of cultured autologous limbal stem cells (LSCs) has revolutionized the treatment of limbal stem cell deficiency (LSCD), a leading cause of vision loss and blindness in corneal disorders, including aniridia. To enhance this approach, they have developed novel small-molecule Wnt mimics that activate Wnt signaling and strengthen the progenitor characteristics of LSCs. Since maintaining stem cell properties during expansion is crucial for successful ocular surface reconstruction, these small molecules hold significant promise for LSCD therapy and the development of new treatments for other corneal epithelial disorders.

Inherited Retinal Dystrophies and Protein Interaction Network Analysis. Most inherited retinal dystrophies (IRDs) are monogenic disorders in which mutations in different causal genes lead to similar clinical manifestations. They hypothesize that the causal genes of a given IRD must be interconnected at the molecular level to drive the shared disease phenotype. To explore this, they developed an algorithm to integrate and analyze these causal genes within a protein interaction network. By dissecting the resulting network, they aim to uncover the underlying molecular mechanisms of IRDs, shedding light on disease pathogenesis and potential therapeutic targets.