The Zhang lab is broadly interested in improving understanding and treatment of blinding eye diseases and takes a variety of approaches to do so. Their long-term strength is in identifying genetic variants that contribute to risk for disease and using animal models to determine the underlying mechanism and new drug targets, and they’ve recently become involved in developing novel ocular drug delivery systems and stem cell therapies.
Professor Zhang and his team have contributed significantly in ophthalmologic disease genetics, stem cell biology and new drug development. They’ve discovered several genes that contribute to significant risk for various forms of macular degeneration, diabetic retinopathy and glaucoma, which are major causes of vision loss in the US and world-wide and are in a process of translating these discoveries into therapeutics.
The group is also interested in developing novel therapeutic approaches for macular degeneration, diabetic retinopathy, and glaucoma. Neurotrophic factors are especially promising, as they prevent photoreceptor loss, but they must be delivered into the vitreous because they wouldn’t reach the retina by other means. Therefore, the challenge is to engineer a delivery system to minimize the need for injections. The Zhang lab has already shown that an encapsulated cell implant is effective, and are working with other CNME investigators to develop even more innovative delivery methods such as nanodevices or nanoparticles.
Zhang and his collaborators’ advances in stably culturing neural precursor cells, both from embryonic stem cells and from fibroblasts (without first de-differentiating them), promise to make the study of neural development and work on regenerative therapies for neural injuries and degenerative diseases progress much faster.
Zhao JJ, Ouyang H, Luo J, Patel S, Xue Y, Quach J, Sfeir N, Zhang M, Fu X, Ding S, Chen S, Zhang K. Induction of retinal progenitors and neurons from mammalian Müller glia under defined conditions. J Biol Chem 2014; 289(17): 11945-51.
Zhang K, Hopkins JJ, Heier JS, Birch DG, Halperin LS, Albini TA, Brown DM, Jaffe GJ, Tao W, Williams GA (2011). Ciliary neurotrophic factor delivered by encapsulated cell intraocular implants for treatment of geographic atrophy in age-related macular degeneration. Proc Natl Acad Sci. 2011; 108(15):6241-5.
Yang Z, Camp NJ, Sun H, Tong Z, Gibbs D, Cameron DJ, Chen H, Zhao Y, Pearson E, Li X, Chien J, Dewan A, Harmon J, Bernstein PS, Shridhar V, Zabriskie NA, Hoh J, Howes K, Zhang K. A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration. Science 2006; 314(5801), 992-3. (see Science New Focus, same issue; Science Breakthoughs of the Year, 2006)