|Associate Professor of Ophthalmology & Visual Science
The Yang lab
Neurobiology of Disease
Pathogenetic mechanisms of retinal degeneration and cell biology of photoreceptors
Retinal degeneration is mainly caused by photoreceptor cell death and retinal pigment epithelium malfunction. It generally includes retinitis pigmentosa and macular degeneration. Although many genes have been identified as responsible for these diseases, their physiological functions and pathogenic mechanisms are not clear. Additionally, many causative genes are still unidentified.
The research in Dr. Yang's laboratory is focused on the disease mechanisms and therapeutic treatments for retinal degenerative diseases using mouse models. Her research group investigates the biological functions of genes whose mutations are known to cause human retinal diseases. Using mouse models for these diseases, the group also studies how to treat these diseases by means of gene therapy. Dr.Yang's team is also interested in cell biology of photoreceptors, especially the cellular processes of intracellular trafficking, structural maintenance, and calcium regulation.
The ongoing research projects in her laboratory are to understand three things: 1. how defects in the multiple protein complex at the periciliary ridge complex in photoreceptors cause retinal degeneration in Usher Syndrome type II, which is a disease with both vision and hearing loss; 2. the biological functions of the ciliary rootlet, a cytoskeletal structure, in photoreceptors and how its defects cause retinal degeneration; 3. how calcium homeostasis is maintained in photoreceptor synaptic terminals and whether it is involved in retinal degeneration.
Chen, Q., Zou, J., Shen, Z., Zhang, W., and Yang, J. (2014) Whirlin and PDZ domain containing 7 (PDZD7) proteins are both required to form the quaternary protein complex associated with Usher syndrome type 2. J Biol Chem, 289(52):36070-36088.
Mathur, P., and Yang, J. (2014) Usher syndrome: hearing loss, retinal degeneration and associated abnormalities. [Review]. BBA - Molecular Basis of Disease, 1852(3):406-420.
Zou, J., Zheng, T., Ren, C., Askew, C., Liu, X., Pan, B., Holt, J.R., Wang, Y., and Yang, J. (2014) Deletion of PDZD7 disrupts the Usher syndrome type 2 protein complex in cochlear hair cells and causes hearing loss in mice. Hum Mol Genet, 23(9):2374-2390.
Green, J.A., Yang, J., Grati, M., Kachar, B., and Bhat, M.A. (2013) Whirlin, a cytoskeletal scaffolding protein, stabilizes the paranodal region and axonal cytoskeleton in myelinated axons. BMC Neurosci, 14:96.
Yang, J. (2012) Usher Syndrome: Genes, Proteins, Models, Molecular Mechanisms, and Therapies. In Sadaf Naz (Ed.), Hearing Loss (pp. 293-328). Rijeka: Intech, ISBN: 978-953-51-0366-0.
Zou, J., Lee, A., and Yang, J. (2012) The expression of whirlin and Ca(v)1.3alpha(1) is mutually independent in photoreceptors. Vision Res, 75:53-59.
Wang, L., Zou, J., Shen, Z., Song, E., and Yang, J. (2012) Whirlin interacts with espin and modulates its actin-regulatory function: an insight into the mechanism of Usher syndrome type II. Hum Mol Genet, 21(3):692-710.
Yang, J., Wang, L., Song, H., and Sokolov, M. (2012) Current Understanding of Usher Syndrome Type II. Frontiers in Bioscience, 17:1165-1183.
Zou, J.H., Luo, L., Shen, Z., Choido, V., Ambati, B.K., Hauswirth, W.W., and Yang, J. (2011) Whirlin replacement restores the formation of the USH2 protein complex in whirlin knockout photoreceptors. Invest Ophthalmol Vis Sci, 52:2343-2351.
Yang, J., Liu, X., Zhao, Y., Adamian, M., Pawlyk, B.S., Sun, X., McMillan, D.R., White, P.C., Liberman, M.C., and Li, T. (2010) Ablation of whirlin long isoform disrupts the USH2 protein complex and causes vision and hearing loss. Plos Genetics, 6:e1000955.
Yang, J., Pawlyk, B., Wen, X., Adamian, M., Soloviev, M., Michaud, N., Zhao, Y., Sandberg,, M.A., Makino, C.L., and Li, T. (2007) Mpp4 is required for proper localization of plasma membrane calcium ATPases and maintenance of calcium homeostasis at the rod photoreceptor synaptic terminals. Human Molecular Genetics, 16:1017-1029.
Yang, J., and Li, T. (2006) Rootletin. Experimental Eye Research, 83:1-2.
Yang, J., Adamian, M., and Li, T. (2006) Rootletin interacts with C-Nap1 and may function as a physical linker between the pair of centrioles/basal bodies in cells. Molecular Biology of the Cell, 17:1033-1040.
Yang, J., and Li, T. (2005) The ciliary rootlet interacts with kinesin light chains and may provide a scaffold for kinesin-1 vesicular cargos. Experimental Cell Research, 309:379-389.
Yang, J., Gao, J., Adamian, M., Wen, X., Pawlyk, B., Zhang, L., Sanderson, M.J., Zuo, J., Makino, C.L., and Li, T. (2005) The ciliary rootlet maintains long-term stability of the sensory cilia. Molecular and Cellular Biology, 25:4129-4137.
Yang, J., Liu, X., Yue, G., Adamian, M., Bulgakov, O., and Li, T. (2002) Rootletin, a novel coiled-coil protein, is a structural component of the ciliary rootlet. Journal of Cell Biology, 159:431-440.