Michael M Wang M.D., Ph.D.
| 7629 Med Sci II, 0622 |
| Ann Arbor, MI 48109 |
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The Wang laboratory focuses on the molecules which participate in neuronal injury, with a specific interest in how specific molecules protect the brain from ischemic injury (stroke).
We are investigating the molecular mechanisms of a unique stroke syndrome, Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). This disorder is caused by mutations in the arterial gene Notch3. Our hope is that studying a stroke disorder caused by a single gene mutation will provide insight into the causes of common stroke. Current studies focus on the proteins than bind to Notch3 and which modulate its function. These proteins are providing insight into the mechanisms of pathogenesis of CADASIL and are shedding light on the fine tuning of Notch signaling.
Another goal is to discover how to modify the outcome of stroke by studying the genes activated by two endogenous agents: estrogen and bone morphogenetic protein-7 (BMP-7). We are investigating the molecular mechanisms of rapid actions of estrogen, and the functional consequences of these non-nuclear actions. BMP-7 is an unusual neuroprotective agent, in that it improves stroke outcome when administered days after the initial injury. We have identified sets of genes which are regulated by BMP-7, and are investigating whether these genes play a role in 1) delayed neuroprotective function; 2) dendritic growth. These studies are being performed collaboratively with the Dr. Pam Lein (OHSU). We hope that our studies will shed light on mechanisms of neuroprotection as well as cellular differentiation and plasticity of innervation.
Wang MM and Reed RR: Molecular cloning of the olfactory neuronal transcription factor Olf-1 by genetic selection in yeast. Nature, 364:121-126, 1993.
Wang MM, Tsai RYL, Schrader, KA and Reed, RR. Genes encoding components of the olfactory signal transduction cascade contain a DNA binding site that may direct neuronal expression. Mol. Cell. Biol., 13:5805-5813, 1993.
Wang MM, Klaus JA, Joh HD, Traystman RJ, Hurn PD. Postischemic angiogenic factor expression in stroke-prone rats. Exp Neurol, 173:283-288, 2002.
Borjigin J, Deng J, Sun X, De Jesus M, Liu T, Wang MM. Diurnal Pineal 3-O-sulphotransferase-2 expression controlled by Beta-adrenergic expression. J Biol Chem. 278:16315-9. 2003.
Xu Y, Traystman RJ, Hurn PD, Wang MM. Neurite localized estrogen receptor-a mediates rapid signaling by estrogen. J Neurosci Res. 2003 74:1-11.
Wang MM, Traystman RJ, Hurn PD, Liu T. Non-classical regulation of estrogen receptor-alpha by ICI182,780. J Steroid Biochem Mol Biol. 2004 Sep;92(1-2):51-62.
Ardelt AA, McCullough LD, Korach KS, Wang MM, Munzenmaier DH, Hurn PD. Estradiol regulates angiopoietin-1 mRNA expression through estrogen receptor-alpha in a rodent experimental stroke model. Stroke. 2005 Feb;36(2):337-41.
Dang L, Fan X, Chaudhry A, Wang M, Gaiano N, Eberhart CG. Notch3 Signaling Initiates Choroid Plexus Tumor Formation, Oncogene, 2006. 25:487-91.
Pin S, Chen HL, Lein PJ, Wang MM. Nucleic acid binding agents exert local toxic effects on neurites via a non-nuclear mechanism, J Neurochemistry, 2006. 96:1253-66.
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