Dongxian Zhang, Ph.D.[La Jolla]
Motor neuron diseases are fatal and cause tremendous mental and physical sufferings in affected people. Sanford-Burnham Medical Research Institute provides an excellent academic environment that we can focus on basic and translational researches aimed at prevention and cure of motor neuron diseases.
Activation of interferon signaling pathways in spinal cord astrocytes from an ALS mouse model.
Wang R, Yang B, Zhang D
Glia. 2011 Jun;59(6):946-58
Memantine prolongs survival in an amyotrophic lateral sclerosis mouse model.
Wang R, Zhang D
Eur J Neurosci. 2005 Nov;22(9):2376-80
Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits.
Chatterton JE, Awobuluyi M, Premkumar LS, Takahashi H, Talantova M, Shin Y, Cui J, Tu S, Sevarino KA, Nakanishi N, Tong G, Lipton SA, Zhang D
Nature. 2002 Feb 14;415(6873):793-8
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Loss of sorting nexin 27 contributes to excitatory synaptic dysfunction by modulating glutamate receptor recycling in Down's syndrome.
Wang X, Zhao Y, Zhang X, Badie H, Zhou Y, Mu Y, Loo LS, Cai L, Thompson RC, Yang B, Chen Y, Johnson PF, Wu C, Bu G, Mobley WC, Zhang D, Gage FH, Ranscht B, Zhang YW, Lipton SA, Hong W, Xu H
Nat Med. 2013 Mar 24;
Dongxian Zhang's Research Focus
Amyotrophic Lateral Sclerosis (Lou Gehrig's Disease), Spinal Muscular Atrophy, Neurodegenerative and Neuromuscular Diseases
The mechanisms underlying the selective death of motor neurons have not been fully investigated in motor neurons diseases like spinal muscular atrophy (SMA) and Amyotrophic Lateral Sclerosis (ALS). Dr. Dongxian Zhang’s research focuses on elucidating molecular events underlying pathogenesis of motor neuron diseases using molecular biology, electrophysiology, pharmacology, and gene profiling. In addition, he explores the possible link of disease-related molecules to pathological conditions of motor neurons through gene targeting. The result of these studies can be utilized to develop drugs and new therapeutic strategies for treatment of motor neuron diseases.
Dongxian Zhang's Research Report
Molecular Mechanisms Underlying Motor Neuron Degeneration
Our research interests focus on mechanisms underlying pathogenesis of motor neuron diseases including early-onset
spinal muscular atrophy
(SMA) and late-onset
Amyotrophic Lateral Sclerosis
(ALS). Using a combination of molecular biology, electrophysiology, gene profiling, and genetic manipulation we are investigating molecular events related to motor neuron degeneration in cell cultures and mouse models. Our goal is to identify molecular targets for early detection and prevention of motor neuron diseases.
N-methyl-D-aspartate (NMDA) receptors are a subtype of glutamate receptors that play a critical role in the development and maintenance of the central nervous system, including the motor system. We have characterized the subunit composition of NMDA receptors in the lower motor neurons, suggesting these receptors may mediate excitotoxicity in the early stage of motor neuron development. We have recently cloned and characterized a novel NMDA receptor subunit, NR3B, that is highly expressed in motor neurons. The NR3B knockout mice generated in our laboratory show the phenotype of an early-onset motor neuron disease that results from a specific degeneration of motor neurons in the early postnatal stage. Further analysis along these lines will provide a molecular basis for understanding the role of the NMDA receptor in motor neuron degeneration.
The mechanisms underlying the selective death of motor neurons have not been fully investigated in ALS research. We hypothesize that the expression level of a specific group of genes is modified at various disease stages leading to selective death in ALS-susceptible motor neurons. We have undertaken gene expression profiling experiments using an animal model of ALS, the superoxide dismutase-1 (SOD1) mutant mouse. Our goal is first to identify a group of disease state-specific genes whose expression levels change in the early pre-symptomatic stage. We will then characterize and finally alter the expression level of three selected genes genetically to further delineate the role they play in motor neuron diseases. These studies will lead to a better understanding of molecular processes linked directly to motor neuron death. Most importantly, these genes would be appropriate targets for developing strategies to treat inherited and sporadic forms of ALS.
About Dongxian Zhang
Dongxian Zhang earned his Ph.D. degree at the University of Texas Medical Branch in Galveston in 1990. From 1990-1993, he received postdoctoral training at Harvard Medical School where he subsequently served as Instructor and conducted research in the departments of Neurology and Surgery. Dr. Zhang joined Sanford-Burnham Medical Research Institute in September 1999. He is also an adjunct Assistant Professor in Department of Molecular Pathology, UCSD, since 2004.