Xian-Jie Yang, Ph.D.

Work Address:
JSEI
Los Angeles, CA 90095 JSEI
Los Angeles, CA 90095

Affiliations
Affiliations
Professor, Ophthalmology
Member, Brain Research Institute, Cell & Developmental Biology GPB Home Area, Gene Regulation GPB Home Area, Neuroscience GPB Home Area, Stein Eye Institute
Research Interests
The main interest of our lab is to understand the molecular and cellular mechanisms underlying development of the vertebrate central nervous system. We use the mouse and chicken retinas as models to study cell fate specification of neural progenitors during development. In addition, we study the maintenance and activation of the adult retinal stem cell niche under conditions that cause retinal degeneration. The mature retina is composed of seven major cell types that are generated from multipotent neural progenitors during neurogenesis. The cell fate choices of uncommitted neural progenitor cells are influenced by both cell-extrinsic cues and cell-intrinsic determinants. We are particularly interested in how extracellular signaling molecules regulate progenitor behaviors through key transcription factors that specify various retinal cell types. Our current studies center around several signaling molecules, including Sonic hedgehog (Shh), vascular endothelial growth factor (VEGF), and ciliary neurotrophic factor (CNTF). Functions of these signaling pathways in retinogenesis are investigated using molecular genetic approaches through tissue-specific gene knockout and knockdown, as well as viral and non-viral gene misexpression. The cell type-specific responses to different extracellular signals are analyzed at cellular and transcriptional levels both in vivo and in primary neuronal culture systems. The goal of these studies is to elucidate how neural progenitor cells integrate and respond to multiple environmental signals during formation of the light sensing retinal neural network. In addition to molecular mechanisms involved in normal neural development, we are investigating cell-cell signaling in the presumptive adult retinal stem cell niche. The roles of various signaling pathways in maintenance and activation of the intrinsic stem cell pool are addressed by molecular genetic analyses in vivo and also tested in neural stem cell cultures in vitro. The potential of signaling molecules in triggering endogenous stem cell amplification is also studied by viral vector-mediated gene delivery. Results from these investigations will enhance our abilities to harness the potential of neural stem cells as therapeutic tools in combating retinal degeneration.
Biography

Xian-Jie Yang is a developmental biologist, who has served on the UCLA School of Medicine faculty since she joined the Department of Ophthalmology in 1996. She is a member of the Molecular Biology Institute, Brain Research Institute, and has become an associate professor in 2003. Dr, Yang obtained her B.S in biology from Beijing Normal University and her Ph.D. from Cornell University in Biochemistry, Cell and Molecular Biology after studying transcription regulation. She pursued her postdoctoral training at Harvard University and Harvard Medical School working on vertebrate neural development. Her research centers on development and diseases of the vertebrate retina, in particular growth factor signaling mechanisms during normal neural differentiation and neuronal survival in retinal degeneration. Her laboratory is also developing cellular and molecular therapies for inherited retinal diseases.

Publications

A selected list of publications:

Sakagami Kiyo, Chen Bryan, Nusinowitz Steven, Wu Hong, Yang Xian-Jie   PTEN regulates retinal interneuron morphogenesis and synaptic layer formation Molecular and cellular neurosciences, 2012; 49(2): 171-83.
Rhee Kun Do, Yang Xian-Jie   Function and mechanism of CNTF/LIF signaling in retinogenesis Advances in experimental medicine and biology, 2010; 664(21): 647-54.
Liao Jo-Ling, Yu Juehua, Huang Kevin, Hu Jane, Diemer Tanja, Ma Zhicheng, Dvash Tamar, Yang Xian-Jie, Travis Gabriel H, Williams David S, Bok Dean, Fan Guoping   Molecular signature of primary retinal pigment epithelium and stem-cell-derived RPE cells Human molecular genetics, 2010; 19(21): 4229-38.
Sakagami, K., Gan, L., and Yang, X.-J.   Distinct effects of Hedgehog signaling on neuronal fate specification and cell cycle progression in the embryonic mouse retina. , J Neurosci , 2009; 29: 6932-6944.
Sakagami Kiyo, Gan Lin, Yang Xian-Jie   Distinct effects of Hedgehog signaling on neuronal fate specification and cell cycle progression in the embryonic mouse retina The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009; 29(21): 6932-44.
Hsieh, Y.-W. and Yang, X.-J.   Dynamic Pax6 expression during the neurogenic cell cycle influences proliferation and cell fate choices of retinal progenitors. , Neural Development , 2009; 4: 32.
Hsieh Yi-Wen, Yang Xian-Jie   Dynamic Pax6 expression during the neurogenic cell cycle influences proliferation and cell fate choices of retinal progenitors Neural development, 2009; 4(10): 32.
Chen, L., Sham, C.W., Chan, A. M., Francisco, L. M., Wu, Y., Mareninov, S., Sharpe, A. H., Freeman, G.J., Yang, X. J., Braun, J., and Gordon, L.K   Role of the immune modulator programmed cell death-1 during development and apoptosis of retinal ganglion cells. , Invest Ophthalmol Vis Sci , 2009; 50: 4941-4948.
Chen Ling, Sham Caroline W, Chan Ann M, Francisco Loise M, Wu Yin, Mareninov Sergey, Sharpe Arlene H, Freeman Gordon J, Yang Xian-Jie, Braun Jonathan, Gordon Lynn K   Role of the immune modulator programmed cell death-1 during development and apoptosis of mouse retinal ganglion cells Investigative ophthalmology & visual science, 2009; 50(10): 4941-8.
Hashimoto, T., Gibbs, D., Lillo, C., Azarian, S.M., Legacki, E., Zhang, X.M., Yang, X.-J.#, and Williams, D. S. # Co-corresponding authors#   Lentiviral gene replacement therapy of retinas in a mouse model for Usher syndrome type 1B. Gene Therapy, Gene Therapy, 2007; 14: 584-594.
Kun Do Rhee, Alberto Ruiz, Jacque L. Duncan, William Hauswirth, Matthew M. LaVail, Dean Bok#, and Xian-Jie Yang# Co-corresponding authors#   Molecular and cellular alterations induced by sustained expression of ciliary neurotrophic factor in a mouse model of retinitis pigmentosa. , Investigative Ophthalmology & Visual Science, 2007; 48: 1389-1400.
Hashimoto, T., Zhang, X.M., Chen, Y. B., and Yang, X.-J.   VEGF activates divergent intracellular signaling components to regulate retinal progenitor cell proliferation and neuronal differentiation. , Development, 2006; 133: 2201-2210.
Goureau, O Rhee, KD Yang, XJ   Ciliary neurotrophic factor promotes muller glia differentiation from the postnatal retinal progenitor pool Developmental neuroscience. , 2004; 26(5-6): 359-70.
Rhee, KD Goureau, O Chen, S Yang, XJ   Cytokine-induced activation of signal transducer and activator of transcription in photoreceptor precursors regulates rod differentiation in the developing mouse retina The Journal of neuroscience : the official journal of the Society for Neuroscience. , 2004; 24(44): 9779-88.
Yang, XJ   Roles of cell-extrinsic growth factors in vertebrate eye pattern formation and retinogenesis Seminars in cell & developmental biology. , 2004; 15(1): 91-103.
Zhang, XM Yang, Z Karan, G Hashimoto, T Baehr, W Yang, XJ Zhang, K   Elovl4 mRNA distribution in the developing mouse retina and phylogenetic conservation of Elovl4 genes Molecular vision [electronic resource]. , 2003; 9: 301-7.
Rhee, KD Yang, XJ   Expression of cytokine signal transduction components in the postnatal mouse retina Molecular vision [electronic resource]. , 2003; 9: 715-22.
Hashimoto, T., Zhang, X.M., and Yang, X.-J   Expression of the Flk-1 receptor and its ligand VEGF in the developing chick central nervous system, Gene Expression Patterns , 2003; 3: 109-113.
Hsieh, YW Zhang, XM Lin, E Oliver, G Yang, XJ   The homeobox gene Six3 is a potential regulator of anterior segment formation in the chick eye Developmental biology. , 2002; 248(2): 265-80.
Zhang, XM Yang, XJ   Regulation of retinal ganglion cell production by Sonic hedgehog Development (Cambridge, England) , 2001; 128(6): 943-57.
Zhang, XM Yang, XJ   Temporal and spatial effects of Sonic hedgehog signaling in chick eye morphogenesis Developmental biology. , 2001; 233(2): 271-90.
Zhang, XM Lin, E Yang, XJ   Sonic hedgehog-mediated ventralization disrupts formation of the midbrain-hindbrain junction in the chick embryo Developmental neuroscience. , 2000; 22(3): 207-16.
Ezzeddine, ZD Yang, XJ DeChiara, T Yancopoulos, G Cepko, CL   Postmitotic cells fated to become rod photoreceptors can be respecified by CNTF treatment of the retina Development (Cambridge, England) , 1997; 124(5): 1055-67.
Cepko, C. L., Austin, C. P., Yang, X.J., Alexiades, M. and Ezzedine, D.   Cell fate determination in the vertebrate retina. , Proc. Natl. Acad. USA , 1996; 93: 589-595.
Yang, XJ and Cepko, CL   Flk-1, a receptor for vascular endothelial growth factor (VEGF), is expressed by retinal progenitor cells The Journal of neuroscience : the official journal of the Society for Neuroscience. , 1996; 16(19): 6089-99.
Argetsinger, L.S., Campbell, G.S., Yang, X.J., Witthuhn, B.A., Silvennoinen, O., Ihle, J.N., and Carter-Su, C.   Identification of JAK2 as a growth hormone receptor-associated tyrosine kinase. , Cell, 1993; 74: 237-244.
Yang, XJ, Chung, D, Cepko, CL   Molecular cloning of the murine JAK1 protein tyrosine kinase and its expression in the mouse central nervous system The Journal of neuroscience : the official journal of the Society for Neuroscience. , 1993; 13(7): 3006-17.
Hsieh Yi-Wen, Zhang Xiang-Mei, Lin Eddie, Oliver Guillermo, Yang Xian-Jie   The homeobox gene Six3 is a potential regulator of anterior segment formation in the chick eye Developmental biology, 2002; 248(2): 265-80.
Hashimoto Takao, Zhang Xiang-Mei, Chen Brenden Yi-kuang, Yang Xian-Jie   VEGF activates divergent intracellular signaling components to regulate retinal progenitor cell proliferation and neuronal differentiation Development (Cambridge, England), 2006; 133(11): 2201-10.
Rhee Kun Do, Goureau Olivier, Chen Shiming, Yang Xian-Jie   Cytokine-induced activation of signal transducer and activator of transcription in photoreceptor precursors regulates rod differentiation in the developing mouse retina The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004; 24(44): 9779-88.
Rhee Kun Do, Nusinowitz Steven, Chao Kevin, Yu Fei, Bok Dean, Yang Xian-Jie   CNTF-mediated protection of photoreceptors requires initial activation of the cytokine receptor gp130 in Müller glial cells Proceedings of the National Academy of Sciences of the United States of America, 2013; 110(47): E4520-9.
Yang Xian-Jie   Roles of cell-extrinsic growth factors in vertebrate eye pattern formation and retinogenesis Seminars in cell & developmental biology, 2004; 15(1): 91-103.
Goureau Olivier, Rhee Kun Do, Yang Xian-Jie   Ciliary neurotrophic factor promotes muller glia differentiation from the postnatal retinal progenitor pool Developmental neuroscience, 2004; 26(5-6): 359-70.
Rhee Kun Do, Ruiz Alberto, Duncan Jacque L, Hauswirth William W, Lavail Matthew M, Bok Dean, Yang Xian-Jie   Molecular and cellular alterations induced by sustained expression of ciliary neurotrophic factor in a mouse model of retinitis pigmentosa Investigative ophthalmology & visual science, 2007; 48(3): 1389-400.