Ph.D. in Molecular Medicine at University of Texas Health Science Center at San Antonio
Stroke is a potentially devastating neurological disorder with high morbidity and mortality. Thrombolytic agents such as tissue plasminogen activator (t-PA) are currently the only drugs available to reverse acute ischemic stroke, but paradoxically reestablishing of circulation by t-PA may initiate reperfusion injury. Therefore, treatments that can limit reperfusion injury are urgently needed. Studies using mouse genetics, experimental stroke models, and selective peptide inhibitors and activators have implicated protein kinase C delta in stroke-induced reperfusion injury, in particular PKC delta expressed in neutrophils (Chou et al., 2004 JCI; Chou & Messing 2005 Trends Cardiovasc Med). Understanding the molecular and cellular actions of PKC delta in reperfusion injury requires the identification of the unique targets of PKC delta in signaling pathways activated by ischemia and reperfusion. We have identified several direct substrates of PKC delta using a novel chemical-genetic approach, and are currently characterizing the roles of these PKC delta substrates in stroke-reperfusion injury.
Chiang, T., Messing, R.O., and *Chou, W.-H. (2011) Mouse model of middle cerebral artery occlusion. Journal of Visualized Experiments 48 (http://www.jove.com/details.php?id=2761) (*corresponding author).
Chou, W.-H., Wang, D., McMahon, T., Qi, Z.-H., Song, M., Zhang, C., Shokat, K.M. and Messing, R.O. (2010) GABAA receptor trafficking is regulated by PKC epsilon and the N-ethylmaleimide-sensitive factor. Journal of Neuroscience 30(42),13955-65.
Chou, W.-H. and Messing, R. O. (2008) Hypertensive encephalopathy and the blood-brain barrier: Is deltaPKC a gatekeeper? Journal of Clinical Investigation 118(1), 17-20.
Chou, W.-H. and Messing, R. O. (2005) Protein kinase C isozymes in stroke. Trends in Cardiovascular Medicine 15(2), 47-51.
Chou, W.-H., Choi, ., Zhang, H., Mu, D., McMahon, T., Kharazia, V. N., Lowell, C. A., Ferriero, D. M. and Messing, R. O. (2004) Neutrophil protein kinase C delta as a mediator of stroke-reperfusion injury. Journal of Clinical Investigation 114(1), 49-56.
Chou, W.-H., Huber, A., Bentrop, J., Schulz, S., Chadwell, L. V., Paulsen, R., and Britt, S. G. (1999) Patterning of the R7 and R8 photoreceptor cells: Evidence for induced and default cell-fate specification. Development 126(4), 607-616.
Chou, W.-H., Hall, K. J., Wilson, D. B., Wideman, C. L., Townson, S. M., Chadwell, L. V., and Britt, S. G. (1996) Identification of a novel Drosophila opsin reveals specific patterning of the R7 and R8 photoreceptor cells. Neuron 17(6), 1101-1115.
Society for Neuroscience
American Stroke Association