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Xiang, Yang (Kevin)
Assistant Professor, Department of Molecular and Integrative Physiology
BS Wuhan University
PhD Oregon Health Sciences University
Research Areas
My lab focuses on the function of a family of GPCRs (adrenergic receptors) in both heart and neurodegeneration diseases (Alzheimer and Parkinson). GPCRs are nature's most versatile biological sensors responding to hormones and neurotransmitters, and mediate the senses of pressure, sight, smell, and taste. Adrenergic receptors (ARs), which transmit signals in both central and peripheral nerve systems, are one of the most extensively characterized and serve as a model system for understanding the structure, cell biology, and physiology of GPCRs. We use in vitro and in vivo systems to determine the structural and cellular basis for more complex functional properties that are only observed in differentiated cells and tissues.
In animal heart, b1 and b2 ARs play unique roles in regulating cardiovascular function, and are associated with heart failure development. We use myocytes and sympathetic ganglia neurons from knockout mice to develop a in vitro adrenergic synapse model, and our studies suggest that functional differences between two receptors are due to their distinct localization relative to synapse formation on post-synaptic surface of myocytes. In neurodegeneration diseases, we have found that amyloid Ab peptide directly activates b2AR to induce cAMP accumulation and gene expression of ApoE, a key proteins involved in Alzheimer Diseases in astrocytes. Another project focuses on the interaction between G-protein receptor kinase 2 (GRK2) and a-synuclein, a key protein in Parkinson Diseases. We try to understand how these events affect the bAR and other GPCR (such as dopamine receptor) signaling and function in neuronal tissues.
Representative Publications
De Arcanelis, V., Soto, D., Xiang, Y., (2008) Phosphodiesterase 4 and phosphotase 2A differentially regulate cAMP/PKA signaling for cardiac myocyte contraction under stimulation of beta1 adrenergic receptor. Mol Pharmacol (Published Online) Wang, Y., De Arcangelis, V., Ramali, B., Jung, Y.S., and Xiang, Y. Norepinephrine and epinephrine induced distinct beta 2 adrenoceptor signaling is dictated by GRK phosphorylation in cardiomyocytes. J Biol. Chem. Jan 25; 283(4):1799-1807 Wang, Y., Lauffer, B., Von Zastrow, M., Kobilka, B., and Xiang Y. 2007. NSF regulates beta 2 adrenoceptors trafficking and signaling in cardiomyocytes. Molecular Pharmacology, 72(2):429-39. Shcherbakova, O.G., Hurt, C.M., Xiang, Y., Dell'acqua, M.L., Zhang, Q., Tsien, R.W., and Kobilka, B.K. 2007. Organization of beta-adrenoceptor signaling compartments by sympathetic innervation of cardiac myocytes. J Cell Biol., 176(4):521-33. Sun, Y., Huang, J., Xiang, Y., Bastepe, M., Juppner, H., Kobilka, B.K., Zhang, J.J., and Huang, X.Y. 2007. Dosage-dependent switch from G protein-coupled to G protein-independent signaling by a GPCR. EMBO J., 26(1):53-64.Previous Publication (in Stanford University):
Xiang, Y., Naro, F., Zoudilova, M., Jin, S.-L., Conti, M., and Kobilka, B. 2005. PDE4D is required for Beta 2AR subtype-specific signaling in cardiac myocytes. Proc. Natl. Acad. Sci. USA, 102(3):909-14. E-pub 2005 Jan 11. Swaminath, G., Xiang, Y., Lee, T.W., Steenhuis, J., Parnot, C., and Kobilka, B., Sequential Binding of Agonists to the Beta 2 Adrenoceptor: Kinetic Evidence for Intermediate Conformational States. J Biol. Chem, 2004. 279(1): p. 686-691.Xiang, Y. and Kobilka, B.K. 2003. The PDZ-binding motif of the Beta 2 adrenoceptor are essential for physiologic signaling and trafficking in cardiac myocytes. Proc. Natl. Acad. Sci. USA, 100(19):10776-81.
Xiang, Y. and Kobilka, B.K. 2003. Myocyte adrenoceptor signaling pathways. Science, 300(5625):1530-2.
Additional Information
Collaborative Projects:
Professor Julia George - The role of a-synuclein on GPCR signaling.
Related Research (By Area):
Aging
Cell Signaling and Communication
Learning, Memory, and Plasticity
Neurological and Psychiatric Conditions
Contact information:
