Zongchao Han, M.D., Ph.D.

The Han laboratory is interested in developing gene therapies for retinal diseases. We are particularly interested in understanding the gene expression patterns that are regulated by the cis-regulatory elements. Some important regulators, such as enhancers, are outside of the core promoter and transcription factors. These non-coding DNA sequences can spread over large distances, making it difficult for a designed vector and its therapeutic gene to mimic. We utilize compacted DNA nanoparticles (NPs) which have the ability to transfer large genetic messages to overcome various technical challenges and to evaluate the translational potential of this technology.

Along with gene therapy, our laboratory has developed a water-soluble antioxidant nanoceria formulation. Our studies have shown promising antioxidant activity, anti-inflammatory response, and anti-angiogenesis both in in vitro and in vivo Age-related Macular Degeneration (AMD) models, indicating the feasibility of using this system as an alternative and novel approach for AMD patients for whom current therapies will not work or are not available. This project could be translatable numerically for treating several other diseases, such as neurodegenerative disorders, tumors, and diabetes, which are limited by current standard approaches.

Another interest of the Han laboratory is to produce a multifunctional NP carrier for specific and efficient gene/drug targeting. We are developing new nano-drug delivery systems that have the capability of carrying multiple imaging, targeting, and therapeutic moieties to restore vision or to target tumor. Project success will provide attractive tools and templates with broad potential for precision medicine not only for ocular disorders but also for other diseases and cancers, such as brain tumors, diabetes mellitus, and vascular diseases, which cannot be achieved with currently standard approaches, and will establish a widely applicable method for targeted-treatment, diagnostic and prognostic biomarkers, and therapeutic targets.

Moreover, we are working on several biocompatible and biodegradable injectable hydrogels for delivering several types of therapeutic agents for sustained release. Using a prolonged release formulation reduces dosing frequency and increases the stability, safety, patient compliance, and convenience of administration. Properties of the injectable hydrogels are tunable and form as a gel in situ after injection through thermosensitive or chemical crosslinking activities. Current active projects include injectable hydrogel formed nanocerias, Car-T cells, and stem cells for AMD, retinoblastoma, and diabetic retinopathy.