Research Areas and Expertise (Shan Ping Yu)

The following description is for potential collaborations with interested PIs at EmoryUniversity and VA Medical Center.

 

Cell death mechanism and treatments of ischemic damage:

  • Cellular and molecular mechanism of ischemic cell death;
  • Novel roles of channels, receptor and Na+,K+-ATPase in apoptosis;

Techniques used and available in the lab:

  • Electrophysiology (patch clamp whole-cell and single channel recordings);
  • Mitochondrial membrane potential, ROS and cell death assays;
  • RT-PCR/Western blot/immunostaining;
  • OGD in vitro and ischemia in animal models;
  • Ca2+ and K+ imaging, …

Selected Publications:

  • Yu, S.P., Yeh, C-H., Sensi, S.L., Gwag, B., Canzoniero, L.M.T., Farhangrazi, Z.S., Ying, H.S., Tian, M., Dugan, L.L. & Choi, D.W. Mediation of neuronal apoptosis by enhancement of outward potassium current. Science 278: 114-117, 1997
  • Yu, S.P., Yeh, C-H., Strasser, U. and Choi, D.W. NMDA receptor mediated K+ efflux and neuronal apoptosis. Science  284: 336-339, 1999
  • Xia, S., Lampe, P.A., Deshmukh, M., Yang, A., Brown, B.S., Rothman, S.M., Johnson, Jr., E.M. and Yu, S.P. Multiple channel interactions explain the protection of sympathetic neurons from apoptosis induced by NGF deprivation. J. Neurosci. 22: 114-122, 2002.
  •    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, Z.Y., Wei, L., and Yu, S.P. Age-related neural degeneration in NF-kB p50-/- mice. Neurosci. 139:965-978, 2006.
  •    Zhou, X., Wei, J., Francis, K.R. and Yu, S.P., Novel role of KCNQ2/3 channels in regulating neuronal cell viability, Cell Death and Different. 18:493-505, 2011
  • Xiao, A.Y., Wei, L., Shuli Xia, Rothman S. and Yu, S.P. Ionic mechanism of ouabain-induced concurrent apoptosis and necrosis in cortical neurons. J. Neurosci. 22: 1350-1362, 2002.
  • Wang, X.Q., Xiao, A.Y., Sheline, C., Hyrc, K., Yang, A.Z., Goldberg, M., Choi, D.W. and Yu, S.P. Apoptotic insults impair Na+, K+-ATPase activity as a mechanism of neuronal death mediated by concurrent ATP deficiency and oxidative stress. J. Cell Science 116:2099-2110, 2003.

 

Regenerative therapy:

  • Stem cell transplantation after ischemic stroke and heart ischemia;
  • Endogenous neurogenesis and angiogenesis promoted by peripheral stimulation/physical therapy and exogenous stem cells;
  • Enhanced trophic supports, cytoprotection, migration and tissue repair by hypoxic preconditioning and ion channel regulations;
  • Intracellular transduction signaling pathways;
  • Short- and long-term functional recovery after ischemic stroke

Techniques used and available in the lab:

  • Adult and neonatal animal models: Ischemic stroke (transient and permanent MCA occlusion, barrel cortex small stroke and severe hemisphere stroke, global brain ischemia, heart ischemia, hindlimb ischemia; retina traumatic injury, sciatic nerve traumatic injury;
  • Stem cell cultures of ES cells/iPS cell and bone marrow mesenchymal stem cells, neuronal differentiation and axonal growth, synaptogenesis;
  • Gene knockout mice and signaling gene knockdown (siRNA);
  • Cell death/proliferation/differentiation assays;
  • Blood flow measurements;
  • Electrophysiology (extracellular recordings in brain slices for integrity of the thalomocortical pathway and intracortical pathway, field potential recordings for learning and memory, i.e. LTP and LTD, mEPSP and mEPSC for synaptic transmission).
  • Functional neurological/behavioral tests: the rotor-rod test for locomotion/balance, sticky dot removal test, cell migration assays in vitro and in vivo, Neurological Severity Scores (NSS) of a battery of motor, sensory, reflex, and balance tests (Table 1). More behavioral and cognitive tests are listed under Pain and Behavioral Research below.

Selected Publications:

  •    Wei, L., Cui, L., Snider, B.J., Rivkin, M., Lee, C-S., Adams, L.D., Gottlieb, D.I., Johnson Jr, E.M., Yu, S.P. and Choi, D.W. Transplantation of embryonic stem cells overexpressing Bcl-2 promotes functional recovery after transient cerebral ischemia. Neurobiol Dis. 19:183-193, 2005.
  • Hu, X., Wei, L., Wang, J-A, Wei, J.F., Zhou, X. and Yu, S.P. Hypoxic preconditioning enhances bone marrow mesenchymal stem cell migration via Kv2.1 channel and FAK activation, Am J Physiol, [Epub ahead of print], PMID: 21562308
  • Whitaker, V.R., Cui, L., Miller, S., Yu, S.P. and Wei, L. Whisker stimulation enhances angiogenesis in the barrel cortex following focal ischemia in mice. J Cereb Blood Flow & Met. 27:57-68, 2006.
  • Hu, X, Yu, SP, Fraser JL, Lu ZY, Ogle, ME, Wang J-A, and Wei, L. Transplantation of hypoxia-preconditioned mesenchymal stem cells improves infarcted heart function via enhanced survival of implanted cells and angiogenesis. J Thoracic Cardiovascular Surgery, 135:799-808, 2008.
  • Cui, L., Jiang, J., Wei, L., Snider, B.J., and Yu, S.P. Transplantation of embryonic stem cells improves nerve repair and functional recovery after severe sciatic nerve axotomy in rats. Stem Cells, 26:1356-1365, 2008
  • Theus, M.H., Wei, L., Cui, L., Frances, K., Hu, X., Keogh, C, and Yu, S.P. 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. 210:656-670, 2008.
  • Li, W-L, Yu, S.P., Ogle, M, and Wei L. Enhanced neurogenesis and cell migration following focal ischemia and peripheral stimulation in mice.  Dev Neurobiol, 68:1474-1486, 2008
  • Jiang J., Wang J., Li, C, Yu SP, Wei L. Dual roles of tumor necrosis factor-alpha receptor-1 in a mouse model of hindlimb ischemia. Vasc Med. 14:37-46, 2009.
  • Li Y., Yu, S.P. Mohamad,O., Genetta T and Wei, L.  Sublethal transient global ischemia stimulates migration of neuroblasts and neurogenesis in mice, Translational Stroke Research, 1:184-196, 2010.
  • Zhou X, Song M, Chen D, Wei L, Yu SP. Potential role of KCNQ/M-channels in regulating neuronal differentiation in mouse hippocampal and embryonic stem cell-derived neuronal cultures. Exp Neurol. 229:471-483, 2011.

Pain and behavioral research

  • Long-term consequence of neonatal pain on brain development and behavioral changes; Role of NMDA receptor NR3A in pain and learning/memory regulation;
  • Anesthetics in cancer pain regulation
  • Inflammatory pain on cognitive functions

Techniques used and available in the lab:

  • NR3A KO mice,
  • Hot plate test and tail flick test,
  • Morris water maze test,
  • Sociability tests for disorders of social behavior and cognitive rigidity;
  • Open field test and defensive withdraw test,
  • Y-maze test;
  • Electrophysiology (whole cell recordings of voltage-gated and ligand-gated channels and receptors, LTP and LTD recordings in brain slices).

Selected Publications:

  • Mohamad, O., Chen, D., Zhang, L., Hofmann, C., Wei, L. and Yu, S.P. Erythropoietin reduces neuronal cell death and hyperalgesia induced by peripheral inflammatory pain in neonatal rats. Molecular Pain, Accepted.
  • Mohamad, O., Song, M., Wei, L. and Yu, SP. Slow in motion but smart in learning: behavioral changes in adult NR3A knockout mice. Nature Neuroscience, submitted.
  • Song, M. Wei, L. and Yu, S.P. Enhanced circuitry activity in peri-infarct cortex contributes to functional improvement after bone marrow mesenchymal stem cell treatment in ischemic stroke. Stroke, submitted.