Faculty
Xiaozhong (Alec) Wang, PhD
Assistant Professor
Biochemistry, Molecular Biology, and Cell Biology
PhD, New York University School of Medicine
Email: awang@northwestern.edu
Phone: (847) 467-4897
Fax: (847) 467-1380
Room: Pancoe Rm 1405
Research Interests
Genetic Analysis of Protocadherin Diversity in the Central Nervous System
The human brain is a massive network of over 100 billion neurons with extraordinary complexity. The function of the neural network relies on precise patterns of neuronal connections. How does a neuron recognize its target(s) and establish correct synaptic contacts? My laboratory is interested in understanding the molecular basis for the precision and complexity of neuronal circuitry in the brain.
Our present work is focused on a large family of newly identified cell adhesion molecules, protocadherins (Pcdhs). The vertebrate Pcdh genes (14 Pcdha, 22 PcdhB and 22 Pcdhy in mouse) have a unique genomic organization that is similar to that of the immunoglobulin gene. These genes consist of “variable” and “constant” exons orientated in a tandem array on a single chromosome and can generate a significant number of diverse cell adhesion molecules through a combination of cell-specific promoter activation and cis- alternative splicing. The expression studies on Pcdh mRNAs and proteins have led to speculation that combinatorial patterns of Pcdh expression might underlie precise patterns of neuronal connectivity. Our initial analyses on Pcdh? null mice and other Pcdhy mutant mice have provided evidence that Pcdhy is essential for vertebrate neural development and may play a role in certain aspects of synaptogenesis.
To understand the molecular and cellular mechanisms of Pcdhy’s function in the development of the vertebrate central nervous system, we have generated multiple genetically modified Pcdhy mouse models. The combination of these genetic tools with biochemical and cell biological approaches provides us a powerful way to dissect the Pcdh? signaling system and determine its role in establishing neuronal connectivity. Ultimately our studies may shed light on how combinatorial surface molecular codes contribute to the specificity and complexity of the neuronal network.
Selected Publications
Proteomic analysis reveals overlapping functions of clustered protocadherins. Han MH, Lin C, Meng S, Wang X. Mol Cell Proteomics. 2009 Oct 20.
PiggyBac transgenic strategies in the developing chicken spinal cord. Lu Y, Lin C, Wang X. Nucleic Acids Res. 2009 Sep 15.
A genetic screen for components of the mammalian RNA interference pathway in Bloom-deficient mouse embryonic stem cells. Trombly MI, Su H, Wang X. Nucleic Acids Res. 2009 Mar;37(4):e34. Epub 2009 Feb 17.
Essential and overlapping functions for mammalian Argonautes in microRNA silencing. Su H, Trombly MI, Chen J, Wang X. Genes Dev. 2009 Feb 1;23(3):304-17. Epub 2009 Jan 27.
alpha- and gamma-Protocadherins negatively regulate PYK2. Chen J, Lu Y, Meng S, Han MH, Lin C, Wang X. J Biol Chem. 2009 Jan 30;284(5):2880-90. Epub 2008 Dec 1.
Wang, X., Weiner, J.A., Levi, S., Craig, A-M., Bradley, A. and Sanes, J.R. Gamma protocadherins are required for survival of spinal interneurons. Neuron. 36, 843-854, 2002.
Wang, X., Su, H, and Bradley, A. Molecular mechanisms governing Pcdh y gene expression: evidence for a multiple promoters and cis- alternative splicing model. Genes & Development 16: 1890-1905, 2002.
Wang, X., Su, H., Copenhagen, L.D., Vaishnav, S., Pieri,F., Shope, C.D., Brownell, W.E., De Biasi, M., Paylor, R. and Bradley, A. Urocortin deficient mice display normal stress-induced anxiety behavior and autonomic control but impaired acoustic startle response. Mol. Cell. Biol. 22, 6605-6610, 2002
Xue, Y.,Wang, X., Li, Z., Gotoh, N., Chapman, D. and Skolnik, E.Y. Mesodermal patterning defect in mice lacking the Ste20 NCK interacting kinase (NIK). Development 128, 1559-1572, 2001
Urano, F., Wang, X., Bertolotti, A., Zhang, Y., Chung, P. Harding, H.P. and Ron, D. Coupling of Stress in the Endoplasmic Reticulum to Activation of JNK Protein Kinases by Transmembrane Protein Kinase IRE1. Science 287, 664-666, 2000.
Su, H., Wang, X. and Bradley, A. Nested chromosomal deletions induced with retroviral vectors in mice. Nature Genetics 24, 92-95, 2000.
View all publications by Alec Wang listed in the National Library of Medicine (PubMed). Past and current IBiS students in blue