Gene and stem cell therapy in brain ischemia/membrane protein structure by NMR.
The research in Dr. Xu's laboratory focuses on (1) rational design of new therapeutic strategies for treatment of brain injury during and after cerebral global ischemia and (2) the molecular mechanisms underlying the actions of low-affinity neurological drugs. In the first project, recent activities have been directed towards the combination of gene and stem cell therapies, with an emphasis on the overexpression of therapeutic proteins and peptides in the brain. The second project involves the 3-D structure and dynamics measurements of the functional segments of human glycine receptor.
Students in Dr. Xu's laboratory have the opportunity to learn a variety of modern techniques, including systemic gene delivery, non-embryonic stem cell transplantation, expression and purification of membrane proteins, high-resolution nuclear magnetic resonance spectroscopy and imaging, imaging reconstruction, 3-D protein structure calculation, and molecular dynamics simulations.
Xu, Y., Liachenko, S.M., Tang, P. and Chan, P.H. Faster Recovery of Cerebral Perfusion in SOD1-Overexpressed Rats after Cardiac Arrest and Resuscitation, Stroke, 40, 2512-8, 2009.
Hirko, A., Dallasen, R., Jomura, S. and Xu, Y. Modulation of Inflammatory Responses after Global Ischemia by Transplanted Umbilical-Cord Matrix Stem Cells, Stem Cells, 26:2893-2901, 2008.
Canlas, C., Ma, D., Li, L., Tang, P. and Xu, Y. Residual Dipolar Coupling Measurements of Transmembrane Proteins Using Aligned Low-q Bicelles and High-Resolution Magic Angle Spinning NMR Spectroscopy, J Am Chem Soc, 130: 13294-13300, 2008.
Ma, D., Tillman, T., Tang, P., Meirovitch, E., Eckenhoff, R., Carnini, A. and Xu, Y. NMR Studies of a Channel Protein Without Membranes: Structure and Dynamics of Water-Solubilized KcsA, Proc Natl Acad Sci USA, 105:16537-16542, 2008.
Jomura, S., Uy, M., Mitchell, K., Dallasen, R., Bode, C. and Xu, Y. Potential Treatment of Cerebral Global Ischemia with Umbilical Cord Matrix Stem Cells, Stem Cells, 25: 98-106, 2007.
Bondarenko, V., Xu, Y. and Tang, P. Structure of the First Transmembrane Domain of the Neuronal Acetylcholine Receptor ?2 Subunit, Biophys J, 92: 1616-1622, 2007.
Liu, Z., Xu, Y. and Tang, P. Steered Molecular Dynamics Simulations of Na+ Permeation across Gramicidin A Channel, J. Phys. Chem. B, 110: 12789-95, 2006.
Yonkunas, M.J., Xu, Y. and Tang, P. Anesthetic Interaction with Ketosteroid Isomerase: Insights from Molecular Dynamics Simulations, Biophys J, 89: 2350-2356, 2005.
Ma, D., Liu, Z., Tang, P. and Xu, Y. Structure and Dynamics of the Second and Third Transmembrane Domains of Human Glycine Receptor, Biochemistry 44: 8790-8800, 2005.
Tang, P. and Xu, Y. Large-Scale Molecular Dynamics Simulations of General Anesthetic Effects on Ion Channel in Fully Hydrated Membrane: Implication of Molecular Mechanisms of General Anesthesia, Proc Natl Acad Sci USA, 99: 16035-16040, 2002.