Chao Tong

Contact Information

Research Interests

My research interest is to study Amyotrophic Lateral Sclerosis (ALS ) using fruit flies as a model system. ALS is a fatal, late onset neurodegenerative disorder associated with the dysfunction or death of motor neurons in brain and spinal cord. Although most cases are classified as sporadic, around 10-15% cases are familial inherited. Since both the sporadic (SALS) and familial ALS (FALS) affect the same group of cells and have similar pathology hallmarks, similar molecular mechanisms may cause FALS and SALS. Several genetic loci involved in FALS have been identified, such as SOD1, VAPB, and alsin. However, the molecular mechanism as to how these mutants cause the disease is far from clear. It is possible that at least some of these molecules function in the same biochemical pathway. My goal is to decipher the molecular mechanism underling ALS and establish a network between different molecules which are implicated in both SALS and FALS. My major focus is the ALS8 protein: VAPB. A corresponding point mutation in VAP-33, the Drosophila VAPB homolog, can mimic some key aspects of the disease and decrease levels of VAPB have also been documented in many sporadic cases, indicating that a malfunction or reduction of VAP may be a general feature of ALS. We have shown that the amino-terminal domain of VAP-33, the MSP (Major Sperm Protein) domain (VAPMSP), is cleaved and secreted into the extracellular space where it functions as a hormone. Currently, I am studying the signaling cascade initiated by VAPMSP.

Publications

Tsuda H, Han SM, Yang Y, Tong C, Lin YQ, Mohan K, Haueter C, Zoghbi A, Harati Y, Kwan J, Miller MA, Bellen HJ (2008) The Amyotrophic Lateral Sclerosis 8 protein VAPB is cleaved, secreted, and acts as a ligand for Eph receptors. Cell 133:963-977.

Zhao Y, Tong C, Jiang J (2007) Transducing the Hedgehog signal across the plasma membrane. Fly 1:333-336.

Tong C, Jiang J (2007) Using immunoprecipitation to study protein-protein interactions in the Hedgehog-signaling pathway. Methods in Molecular Biology 397:215-229.

Zhao Y*, Tong C*, Jiang J (2007) Hedgehog regulates smoothened activity by inducing a conformational switch. Nature 450:252-258. (* equal contribution)

Jia J, Zhang L, Zhang Q, Tong C, Wang B, Hou F, Amanai K, Jiang J (2005) Phosphorylation by double-time/CKIε and CKIα targets cubitus interruptus for Slimb/β-TRCP-mediated proteolytic processing. Developmental Cell 9:819-830.

Zhang W, Zhao Y, Tong C, Wang G, Wang B, Jia J, Jiang J (2005) Hedgehog-regulated Costal2-kinase complexes control phosphorylation and proteolytic processing of Cubitus interruptus. Developmental Cell 8:267-278.

Jia J*, Tong C*, Wang B, Luo L, Jiang J (2004) Hedgehog signalling activity of Smoothened requires phosphorylation by protein kinase A and casein kinase I. Nature 432:1045-1050. (* equal contribution)

7: Moskalenko S, Tong C, Rosse C, Mirey G, Formstecher E, Daviet L, Camonis J, White MA (2003) Ral GTPases regulate exocyst assembly through dual subunit interactions. Journal of Biological Chemistry 278:51743-51748.

Jia J, Tong C, Jiang J (2003) Smoothened transduces Hedgehog signal by physically interacting with Costal2/Fused complex through its C-terminal tail. Genes and Development 17:2709-2720.

Tong C, Fan HY, Chen DY, Song XF, Schatten H, Sun QY (2003) Effects of MEK inhibitor U0126 on meiotic progression in mouse oocytes: microtuble organization, asymmetric division and metaphase II arrest. Cell Research 13:375-383.

Fan HY, Tong C, Teng CB, Lian L, Li SW, Yang ZM, Chen DY, Schatten H, Sun QY (2003) Characterization of Polo-like kinase-1 in rat oocytes and early embryos implies its functional roles in the regulation of meiotic maturation, fertilization, and cleavage. Molecular Reproduction and Development 65:318-329.

Fan HY, Tong C, Lian L, Li SW, Gao WX, Cheng Y, Chen DY, Schatten H, Sun QY (2003) Characterization of ribosomal S6 protein kinase p90rsk during meiotic maturation and fertilization in pig oocytes: mitogen-activated protein kinase-associated activation and localization. Biology of Reproduction 68:968-977.

Cheng Y, Fan HY, Wen DC, Tong C, Zhu ZY, Lei L, Sun QY, Chen DY (2003) Asynchronous cytoplast and karyoplast transplantation reveals that the cytoplasm determines the developmental fate of the nucleus in mouse oocytes. Molecular Reproduction and Development 65:278-282.

Yao LJ, Fan HY, Tong C, Chen DY, Schatten H, Sun QY (2003) Polo-like kinase-1 in porcine oocyte meiotic maturation, fertilization and early embryonic mitosis. Cellular and Molecular Biology (Noisy-le-Grand, France) 49:399-405.

Fan HY, Li MY, Tong C, Chen DY, Xia GL, Song XF, Schatten H, Sun QY (2002) Inhibitory effects of cAMP and protein kinase C on meiotic maturation and MAP kinase phosphorylation in porcine oocytes. Molecular Reproduction and Development 63:480-7.

Fan HY, Tong C, Li MY, Lian L, Chen DY, Schatten H, Sun QY (2002) Translocation of the classic protein kinase C isoforms in porcine oocytes: implications of protein kinase C involvement in the regulation of nuclear activity and cortical granule exocytosis. Experimental Cell Research 277:183-191.

Tong C, Fan HY, Lian L, Li SW, Chen DY, Schatten H, Sun QY (2002) Polo-like kinase-1 is a pivotal regulator of microtubule assembly during mouse oocyte meiotic maturation, fertilization, and early embryonic mitosis. Biology of Reproduction 67:546-554.