Jing Yang, Ph.D.

Gender:

• Male

Languages Spoken:

• English

Research Center:

• Center for Molecular and Human Genetics

Areas of Interest:

• Modern developmental biology studies have demonstrated that the vast majority of cell fate decisions during embryonic development are controlled by a small number of signaling pathways. Interestingly, these signaling pathways are often involved in adult tissue homeostasis as well. Dysregulation of these signaling pathways has severe consequences in humans, ranging from birth defects to a variety of diseases, including tumorigenesis. Studying functions and regulations of major developmental signaling pathways in embryo will provide fundamental insights into molecular mechanisms of embryonic development and identify potential therapeutic targets for many human diseases. Recent studies have highlighted a major role of reversible protein phosphorylation in operating most signaling transduction pathways. Reversible protein phosphorylation is controlled by protein kinases, which induce phosphorylation of proteins, and protein phosphatases, which dephosphorylate their targets. While many protein kinases have been extensively studied, functions and regulation of protein phosphatases remain poorly understood. My laboratory studies molecular mechanisms of early embryonic development with a focus on protein phosphatase 2A. Specifically, we have been studying B56e regulatory subunit of PP2A. Our recent studies demonstrate that during embryonic development, B56e plays pivotal roles in axis specification, maternal to zygotic transition, and pattern formation of the neural ectoderm. In well-controlled studies, we were able to assign specific roles of B56e into the Wnt, Hedgehog, and IGF pathways. Not surprisingly, B56e undergoes extensive post-transcriptional regulation. We have identified several isoforms of B56?, including an alternative translation isoform and a proteolytic cleavage product of B56e. Currently, we are actively pursuing our B56e studies. We believe that our studies will result in a better understanding of molecular mechanism by which developmental signaling pathways are operated and identify fundamental aspects of growth and differentiation that can be used to address clinical problems.
• Functions of B56e during the maternal to zygotic transition (MZT) The MZT is the first critical developmental transition following fertilization and is characteristic of a dramatic epigenetic change in regulation of gene expression. Prior to the MZT, the zygotic genome is globally silenced by a number of epigenetic regulators, including DNA methylation, histone modifications, and nucleosome remodeling. Disruption of these mechanisms in human causes profound, multi-system developmental disorders, including Rett, Rubinstein-Taydi, Williams, and Beckwith-Wiedeman syndromes. During the MZT, maternal gene products are destructed in a well-controlled manner, allowing the proper activation of the zygotic genome. Understanding mechanisms governing the reprogramming of gene expression during the MZT will provide fundamental insights into epigenetic regulation of gene expression and shed light on human multi-system developmental disorders. Our recent studies indicate that B56e is an essential regulator of the MZT. Depletion of B56e delays zygotic genome activation and degradation of maternally deposited gene products. Currently, mechanisms governing vertebrate MZT remain poorly understood. Triggered by the observation that B56e regulates the MZT, we have performed a genome-wide screen and have successfully identified more than 20 potential MZT regulators. Currently, we are characterizing the MZT candidate genes identified from our genome-wide screen. We will perform an epistasis analysis and assemble B56e and other MZT regulators into a regulatory pathway or network.
• Functions of B56e during pattern formation of the neural ectoderm Pattern formation of the neural ectoderm is one of the most important events during neural development. As the consequence of neural tube patterning, neural cells acquire their initial identities according to their positions along the dorsal-ventral and anterior-posterior axes of the neural tube. Our studies demonstrated that B56e is essential for neural tube patterning. Knockdown of B56e impairs eye induction, eye field separation, ventral midline development, and formation of the midbrain-hindbrain boundary. During eye field separation and ventral midline development, B56e mediates Hedgehog signaling. We were able to show that B56e regulates the Hedgehog pathway at the level of Gli. Currently, we are exploring molecular mechanism through which B56? and its binding partner regulate Hedgehog signaling during pattern formation of the neural ectoderm.

Undergraduate

• University of Sichuan, Sichuan, China
  Date Completed: 06/30/1992

Post Doctoral

• Shanghai Institute of Biochemistry
  Date Completed: 06/30/1998

Fellowship

• Shanghai Institute of Biochemistry
  Date Completed: 06/30/2000

2004–present

• Assistant Professor, Department of Pediatrics, The Ohio State University College of Medicine

2004–present

• Principal Investigator, The Research Institute at Nationwide Children’s Hospital

2000–2004

• Research Associate (Postdoctoral Fellow)
  HHMI, University of Pennsylvania

• Jin Z, Wallace L, Harper SQ, and Yang J. 2010. PP2A:B56 epsilon, a substrate of caspase-3, regulates p53-dependent and -independent apoptosis during development.  J Biol. Chem.. Vol. 45, no. 285. (November): 34493-34502. (IF: 5.328) (Unspecified)
• Wallace LM, Garwick SE, Mei W, Belayew A, Coppee F, Ladner KJ, Guttridge D, Yang J, Harper SQ. 2010. DUX4, a candidate gene for facioscapulohumeral muscular dystrophy, causes p53-dependent myopathy in vivo.  Annals of Neurology. no. in press. (IF: 9.317)
• Yu X, Espinoza-Lewis R, Sun C, Lin L, He F, Xiong W, Yang J, Wang A, Chen Y. 2010. Overexpression of Constitutively Active BMP Receptor-IB in Mouse Skin Causes Ichthyosis vulgaris-like Disease.  Cell and Tissue Res.. Vol. 3, no. 342. : 401-410. (IF: 2.308)
• Jing Yang and Christopher Phiel. 2010. Functions of B56-containing PP2As in major developmental and cancer signaling pathways.  Life Sciences. Vol. (23-26), no. 87. : 659-666. (IF: 2.56)
• Jin Z, Shi J, Saraf A, Mei W, Zhu G, Strack S, Yang J. 2009. The 48 kDa alternative translation isoform of PP2A:B56 epsilon is required for Wnt signaling during midbrain-hindbrain boundary formation.  J Biol. Chem.. Vol. 284. : 7190-7200. (IF: 5.328)
• Yang J, Chan C, Jiang B, Yu X, Chen Y, Barnard J, Mei W. 2009. hnRNP I inhibits Notch signaling and regulates intestinal epithelial homeostasis in the zebrafish.  PLoS Genetics. Vol. 5. : e1000363. (IF: 9.532)
• Espinoza-Lewis RA, Yu L, He F, Liu H, Tang R, Shi J, Sun X, Martin JF, Wang D, Yang J, Chen Y. 2009. Shox2 is essential for the differentiation of cardiac pacemaker cells by repressing Nkx2-5.  Dev. Biol.. Vol. 327. : 376-385. (IF: 4.379)
• Yu X, He F, Zhang T, Espinoza-Lewis RA, Lin L, Yang J, Chen Y. 2008. Cerberus functions as a BMP agonist to synergistically induce nodal expression during left-right axis determination in the chick embryo.  Dev Dyn.. Vol. 237, no. 12. (December): 3613-3623. (IF: 2.833)
• Shi J, Mei W, Yang J. 2008. Heme metabolism enzymes are dynamically expressed during Xenopus embryonic development.  BioCell.. Vol. 32, no. 3. : 259-263. (IF: 0.426)
• Huang Y, Fan J, Yang J, Zhu G. 2008. Suppressed expression of GPR56 protein in human pancreatic cancer cells.  Mol. Cell. Biochem.. Vol. 308, no. 1-2. : 133-139. (IF: 1.896)
• Fan J, Akabane H, Zheng X, Zhou X, Zhang L, Liu Q, Zhang YL, Yang J, Zhu GZ. 2007. Male germ cell-specific expression of a novel Patched-domain containing gene Ptchd3.  Biochemical and Biophysical Research Communications. Vol. 363, no. 3. : 757-761. (IF: 2.548)
• Yu L, Liu H, Yan M, Yang J, Long F, Muneoka K, Chen Y. 2007. Shox2 is required for chondrocyte proliferation and maturation in proximal limb skeleton.  Developmental Biology. Vol. 306, no. 2. : 549-559. (IF: 4.379)
• Rorick AM, Mei W, Liette NL, Phiel C, El-Hodiri HM, Yang J. 2007. PP2A:B56epsilon is required for eye induction and eye field separation.  Developmental Biology. Vol. 302, no. 2. : 477-493. (IF: 4.379)
• Wu J, Yang J, Klein PS. 2005. Neural crest induction by the canonical Wnt pathway can be dissociated from anterior-posterior neural patterning in Xenopus.  Dev Biol.. Vol. 279, no. 1. : 220-32. (IF: 4.379)
• Yang J, Wu J, Tan C, Klein PS. 2003. PP2A:B56e is required for Wnt/ß-catenin signaling during embryonic development.  Development. Vol. 130. : 5569-5578. (IF: 7.194)
• Tang K, Yang J, Gao X, Wang C, Liu L, Kitani H, Atsumi T, Jing N. 2002. Wnt-1 promotes neuronal differentiation and inhibits gliogenesis in P19 cells.  Biochem Biophys Res Commun. Vol. 293, no. 1. : 167-73. (IF: 2.548)
• Yang J, Mei W, Otto A, Xiao L, Tao Q, Geng X, Rupp RA, Ding X. 2002. Repression through a distal TCF-3 binding site restricts Xenopus myf-5 expression in gastrula mesoderm.  Mech Dev. Vol. 115, no. 1-2. : 79-89. (IF: 2.827)
• Yang J, Tan C, Darken RS, Wilson PA, Klein PS. 2002. ß-catenin/Tcf regulated transcription prior to the midblastula transition.  Development. Vol. 129. : 5743-5752. (IF: 7.194)
• Mei W, Yang J, Tao Q, Geng X, Rupp RA, Ding X. 2001. An interferon regulatory factor-like binding element restricts Xmyf-5 expression in the posterior somites during Xenopus myogenesis.  FEBS Lett. Vol. 505, no. 1. : 47-52. (IF: 3.541)
• Yang J, Cheng L, Yan Y, Bian W, Tomooka Y, Shiurba R, Jing N. 2001. Mouse nestin cDNA cloning and protein expression in the cytoskeleton of transfected cells.  Biochim Biophys Acta. Vol. 1520, no. 3. : 251-4. (IF: 3.475)
• Gao X, Bian W, Yang J, Tang K, Kitani H, Atsumi T, Jing N. 2001. A role of N-cadherin in neuronal differentiation of embryonic carcinoma P19 cells.  Biochem Biophys Res Commun. Vol. 284, no. 5. : 1098-1103. (IF: 2.548)
• Tan C, Deardorff MA, Saint-Jeannet JP, Yang J, Arzoumanian A, Klein PS. 2001. Kermit, a frizzled interacting protein, regulates frizzled 3 signaling in neural crest development.  Development. Vol. 128, no. 19. : 3665-74. (IF: 7.194)
• Yan Y, Yang J, Bian W, Jing N. 2001. Mouse nestin protein localizes in growth cones of P19 neurons and cerebellar granule cells.  Neurosci Lett.. Vol. 302, no. 2-3. : 89-92. (IF: 1.925)
• Yang J, Bian W, Gao X, Chen L, Jing N. 2000. Nestin expression during mouse eye and lens development.  Mech Dev. Vol. 94, no. 1-2. : 287-91. (IF: 2.827)
• Tao Q., Yang J., Mei W., Geng X., Ding X. 1999. Cloning and analysing of 5 ' flanking region of Xenopus organizer gene noggin.  Cell Research. Vol. 9, no. 3. : 209-216. (IF: 8.151)