Title:

Associate Professor

Education
Capital Institute of Medicine, Institute of Pharmacology and Toxicology, Beijing, China 
Doctor of Medicine and Masters of Science, Pharmacology, 1982 
State University of New York, Doctor of Philosophy, 1990

Description of Research Program
Our investigation revealed that, in addition to calcium regulation, potassium homeostasis is a critical factor in apoptosis. In the potassium mechanism of apoptosis, a pro-apoptotic K+ efflux and intracellular K+ depletion is essential for activation of apoptotic cascade.  Excessive K+ efflux may be mediated by over-activated voltage-gated K+ channels such as the Kv2.1 channel and glutamate receptors such as NMDA and AMPA receptors. Our further investigations have shown that dysfunction of the Na+/K+-ATPase is a key event in the K+ regulation of apoptosis.  We are currently studying the ionic mechanism underlying different types of cell death, including apoptosis, necrosis, and hybrid death (i.e. concurrent apoptosis and necrosis in the same cells). We are interested in the modulation of voltage-gated and ligand-gated ion channels and membrane transporters under normal and pathological conditions. A variety of techniques are applied in our research, including patch clamp recordings of whole-cell and single-channel configuration, dye imaging, immunohistochemistry, molecular/cellular biology, and cytotoxicity in cultured cells as well as in animal models.  Another major focus in the lab is stem cell research. We are interested in neuronal differentiation of stem cells and novel strategies for enhancing the survival of stem cell-derived neural progenitor cells. Out ultimate goal is to promote the therapeutic potential of stem cell transplantation for ischemic stroke.

Selected Publications
 Theus, MH., Wei, L., Cui, L., Frances, K., Hu, X., Keogh, C, and Yu, SP. In vitro hypoxic preconditioning of embryonic stem cells as a strategy of promoting cell survival and functional benefits after transplantation into the ischemic rat brain. Exp. Neurol. 2008, In press. 

     Theus, MH, Wei, L. and Yu, SP. Critical roles of Src family tyrosine kinases in neuronal differentiation of embryonic stem cells. Exp Cell Res. 312:3096-3107, 2007.

     Takata, T, Hood, AY and Yu, SP.  Voltage-dependent and Src kinase-mediated selective regulations of NMDA receptor single channel inward and outward activities in cortical neurons. Cell Biochemistry & Biophysics. 47:257-270, 2007.

Wei, L, Han, BH, Li Y, Keogh, CL, Holtzman, DM and Yu, SP. Cell death mechanism and protective effect of erythropoietin after focal ischemia in the whisker-barrel cortex of neonatal rats. J Pharmacol Exp Ther. 317:109-116, 2006.

Lu, ZY, Wei, L., and Yu, SP. Age-related neural degeneration in NF-kB p50^-/- mice. Neurosci. 139:965-978, 2006.

Wei, L., Han, BH, Li, Y., Keogh, CL, Holtzman, DM and Yu, SP. Cell death mechanism and protective effect of erythropoietin after focal ischemia in the whisker-barrel cortex of neonatal rats. J Pharmacol Exp Ther. 317:109-116,
2006.

Wang, XQ. and Yu, SP. Novel regulation of Na, K-ATPase by Src tyrosine kinases in cortical neurons. J Neurochem. 93:1515-1523, 2005.Yu, SP. Regulation and critical role of potassium homeostasis in apoptosis. Prog Neurobiol. 70:363-386, 2003.

Yu, SP. Na+, K+-ATPase: the new face of an old player in pathogenesis and apoptotic/hybrid cell death. Biochem Pharmacol. 66:1601-1609, 2003.

Wang, XQ, Xiao, AY, Sheline, C., Yang, AZ, Choi, DW and Yu, SP. Apoptotic insults impair Na+, K+-ATPase activity as a mechanism of neuronal death mediated by concurrent ATP deficiency and oxidant stress.  J. Cell Science, 116:2099-2110, 2003.

Wei, L., Yu, SP, Gottron, F, Snider, J and Choi, DW. Potassium channel blockers attenuate hypoxia- and ischemia-induced neuronal death in vitro and in vivo. Stroke. 34:1281-1286, 2003.

Wang, XQ, Xiao, AY, Yang, A, LaRose, L, Wei, L. and Yu, SP. Block of Na+, K+-ATPase and induction of hybrid death by 4-Aminopyridine in cultured cortical neurons.  J Pharmacol Exp Ther, 305:502-506, 2003.

Xiao, AY, Wei, L., Xia, S, Rothman S and Yu, SP. Ionic mechanism of ouabain-induced concurrent apoptosis and necrosis in cortical neurons. J Neurosci 22:1350-1362, 2002.

Xia, S, Lampe, PA, Deshmukh, M, Yang, A, Brown, BS, Rothman, SM, Johnson, Jr., EM. and Yu, SP. Multiple channel interactions explain the protection of sympathetic neurons from apoptosis induced by NGF deprivation. J Neurosci 22:114-122, 2002.

Yu, SP, Canzoniero, LMT. and Choi, DW. Ion homeostasis and apoptosis. Current Opinion in Cell Biol. 13:405-411, 2001.

Yu, SP and Choi, DW. Ion, cell volume and apoptosis. Proc. Natl. Acad. Sci. USA, 97:9360-9362, 2001.

Yu, SP, Yeh, C-H, Strasser, U and Choi, DW. NMDA receptor mediated K+ efflux and neuronal apoptosis. Science  284:336-339, 1999.

Yu, SP, Yeh, C-H, Sensi, SL, Gwag, B, Canzoniero, LMT, Farhangrazi, ZS, Ying, HS, Tian, M, Dugan, LL and Choi, DW. Mediation of neuronal apoptosis by enhancement of outward potassium current. Science 278:114-117, 1997.