Faculty Profiles

 

Current Research:
The Wang laboratory focuses on the molecules which participate in neuronal injury, with a specific interest in genetic causes of stroke and molecular mechanisms of neuroprotection. One of the major foci of the lab is investigating mutations in Notch3 that cause an inherited disorder called CADASIL.  We are creating cell and transgenic models to understand the proteins and processes that result in vascular defects in CADASIL.  We have identified novel protein-protein with Notch3 and are probing the cellular role for these interactions.

 

In addition, our 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). Estrogen is markedly protective in animals which receive experimental stroke, though its action is controversial. This hormone triggers a change in transcription within neurons; however, it is also clear that it can stimulate rapid activation of protein kinase cascades. We have demonstrated that the estrogen receptor localizes to axons and dendrites and show that local protein kinase activation occurs at punctuate sites within neuritic process. We are investigating the molecular mechanisms of this rapid action 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. BMP-7 also stimulates dendrite growth in cultured neurons and part of its delayed protective action may be linked to this unique function. In close collaboration with Dr. Pam Lein at Oregon Health Sciences University, our groups have identified and are characterizing 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. We hope that our studies will shed light on mechanisms of neuroprotection as well as cellular differentiation and plasticity of innervation.

 

Representative Publications:
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, 74:1-11.  2003.

 

Xu Y, Traystman RT, Hurn PD, Wang MM. "Membrane Restraint of Estrogen Receptor- Enhances Estrogen Dependent Nuclear Localization and Genomic Function." Mol. Endocrinology, 18:86-96.  2003.

 

Wang MM, Traystman RJ, Hurn PD, Liu T. "Non-Classical Regulation of Estrogen Receptor-by ICI182,780." Journal of Steroid Biochemistry and Molecular Biolog, 92:51-62, 2004.

 

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, 36:337-341, 2005.

 

Li H, Pin S, Zeng ZY, Wang MM, Andreasson KA, McCullough LD. "Sex Differences in Cell Death." Annals of Neurology, 58:317-21, 2005.

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