Xin Zhang, Ph.D.
Associate Professor, Medical and Molecular Genetics
David D. Weaver Investigator
- Ph.D. Johns Hopkins University (1998)
- Research Fellow, Brigham and Women's Hospital, Harvard Medical School (1997-2002)
- Instructor, Harvard Medical School (2003)
The main focus of our research is the mechanism of cell signaling during eye development. The eye is a prominent system to study signal transduction, not only because of its biomedical significance, but also because of the rich resource of experimental tools available in the eye research. Previous studies have also identified multiple signaling pathways such as FGF and BMP signaling in mediating the cellular interactions in the eye. However, the specific signaling components of these pathways and their precise in vivo functions in the eye remain poorly understood. With the advent of genome wide research and the rapidly expanding collection of mouse models, it has now become increasingly important to determine the in vivo function of every mouse gene by genetic approaches. We would therefore like to employ the formidable mouse genetic tools to ultimately determine the signaling pathways governing eye development.
Our research also straddles the interfaces of developmental biology, glycobiology and cancer biology, which presents a unique opportunity to discover the mechanism by which glycoprotein and oncogenes regulate developmental processes. In particular, we have employed gene targeting techniques to specifically disrupt the synthesis of heparan sulfate, a cell surface polysaccharide functionally important for multiple intercellular signaling. This allows us to demonstrate that N-sulfation of heparan sulfate plays an essential role in modulating FGF signaling during eye development. Recently, we have also investigated Shp2 protein-tyrosine phosphatase, illuminating its essential in controlling FGF induced Ras-MAPK signaling pathway in the eye. These studies demonstrate the power of genetic approach in dissecting signaling pathways which are not only essential for embryonic development but also functionally important for congenital syndrome and cancer biology.
Qu X, Pan Y, Carbe C, Powers A, Grobe K, Zhang X. 2012. Glycosaminoglycan-dependent restriction of FGF diffusion is necessary for lacrimal gland development. Development. 139, 2730-2739.
Carbe C, Hertzler K, Zhang X. 2012. The functional role of the Meis/Prep-binding elements in Pax6 locus during pancreas and eye development. Developmental Biology. 363(1):320-9.
Cai Z, Simons DL, Fu XY, Feng GS, Wu SM, Zhang X. 2011. Loss of Shp2-mediated MAPK signaling in Müller glial cells results in retinal degeneration. Molecular and Cellular Biology. 31:2973-2983.
Qu X, Hertzler K, Pan Y, Grobe K, Robinson ML, Zhang X. 2011. Genetic epistasis between heparan sulfate and FGF-Ras signaling controls lens development. Developmental Biology. 355:12–20.
*Qu X, Carbe C, Tao C, Powers A, Lawrence R, van Kuppevelt TH, Cardoso WV, Grobe K, Esko JD, Zhang X. 2011. Lacrimal gland development and Fgf10-Fgfr2b signaling is controlled by 2-O and 6-O sulfated heparan sulfate. Journal of Biological Chemistry. 286(16):14435-14444. *Rated at the top 2% of published articles in biology and medicine by the Faculty of 1000 (F1000).
Carbe C and Zhang X. 2011. Lens induction requires attenuation of ERK signaling by Nf1. Human Molecular Genetics. 20(7):1315–1323.
Cai Z, Feng GS, Zhang X. 2010. Temporal requirement of the protein tyrosine phosphatase Shp2 in establishing the neuronal fate in early retinal development. Journal of Neuroscience. 30(11):4110–4119.
Pan Y, Carbe C, Powers A, Feng GS, Zhang X. 2010. Sprouty2 modulated Kras signaling rescues Shp2 deficiency during lens and lacrimal gland development. Development. 137:1085-1093.
Pan Y, Carbe C, Powers A, Zhang EE, Esko JD, Grobe K, Feng GS, Zhang X. 2008. Bud specific N-sulfation of heparan sulfate regulates Shp2 dependent FGF signaling during lacrimal gland induction. Development, 135:301-310.
Zhang X, Rowan S, Yue Y, Heaney S, Pan Y, Brendolan A, Selleri L, Maas RL. 2006. Pax6 is regulated by Meis and Pbx homeoproteins during pancreatic development. Developmental Biology 300:748-757.
Pan Y, Woodbury A, Esko JD, Grobe K, Zhang X. 2006. Heparan sulfate biosynthetic gene Ndst1 is required for FGF signaling in early lens development. Development 133:4933-4944.
Zhang X, Friedman A, Purcell P, Heaney S, Maas RL. 2002. Meis homeoproteins directly regulate Pax6 during vertebrate lens morphogenesis. Genes & Development 16(16):2097-2107.