Dr. Yu's Research Summary
Shan Ping Yu, M.D., Ph.D.
Professor and O. Wayne Rollins Chair in Anesthesiology & Pain Medicine
Over the past 20 years, Dr. Yu’s research has focused on modulations of ion channels and membrane transporters in normal and pathological conditions. In recent years, his investigation has extended to
the ionic and molecular mechanisms of cell death (apoptosis and necrosis) that occur in diseases
such as ischemic stroke and in stem cell transplantation therapy.
Research Progress in the last 10 years:
- A novel study on the ionic mechanism of neuronal apoptosis: in a series of papers, we
reported for the first time that 1) Excessive K+ efflux via the up-modulated delayed rectifier potassium channel (IK) mediated caspase activation, DNA damage, and certain forms of apoptosis; 2) K+ channel blockers attenuated apoptotic cell death in neuronal cultures as
well as in ischemic animals (Yu et al., Science, 1997; Yu et al., Neurobiol. Dis, 1998; Yu
et al., J. Neurochem., 1999; Wang et al., J. Pharmocol. Exp. Ther., 2000, Abdallah et al., 2006).
- A novel study on the NMDA receptor channel-mediated outward K+ current and its unique voltage-dependent but Ca2+-independent regulation (Yu et al., Science, 1999; Ichinose,
Wang & Yu. J. Physiol, 2003; Takata et al., Cell Biochem. Biophysic. 2007). This was
the first report that revealed a pathological role of the potassium permeability of NMDA
receptors. This mechanism may play a key role in neuronal apoptosis in ischemic stroke.
- A novel study on the tyrosine kinase regulation of Na+, K+-ATPase and its relationship to apoptosis (Xiao et al., Brain Res., 2002; Wang et al., J. Cell Sci., 2004; J. Neurochem.,
2003). This was the first systematic investigation on the mechanism of ouabain toxicity and
has led to the identification of a new type of cell death, the “hybrid cell death”.
- Demonstration of the new concept of ”hybrid death” of simultaneous apoptotic and necrotic components in the same cells induced by blocking the Na+, K+-ATPase and after ischemic stroke, correlating to intracellular K+ depletion and intracellular accumulation of Ca2+ and Na+ (Xiao et al., J. Neurosci., 2002; Xiao et al., Brain Res., 2002; Wei et al., Brain Res., 2004).
- Electrophysiological demonstration of the pathological regulation of Na+-Ca2+ exchanger and
its significance in excitotoxicity (Yu, & Choi, Eur. J. Neurosci., 1997; 1997; Sensi et al., J. Neurosci., 1997).
- A novel study of membrane-delimited modulation of NMDA receptor channels by
metabotropic glutamate receptors (Yu et al., J. Physiol., 1997).
- Drug discovery of a new therapeutic treatment for cell death in stroke and degenerative
diseases (Xia, Lampe, Deshmukh, Yang, Brown, Rothman, Johnson & Yu. J. Neurosci.
2002; Yu et al., Stroke. 2003; Wei et al., Eur J Physiol., 2004;Yang et al., Pharmacol.,
2005; Li et al., J Cereb Blood Flow Metab, 2007).
- Demonstration of the critical role of Src kinases in embryonic stem cell neuronal differentiation (Theus et al., Exp. Cell Res., 2006). This work will allow us to have a better understanding and may even manipulate the molecular mechanism that controls neuronal differentiation of embryonic stem cells.
- A series of investigations on the novel application of hypoxic preconditioning on stem cell transplantation (Theus et al., Exp Neurol. 2007, 2005; Hu et al., J Thoracic Cardiovascular Surgery, 2007). This investigation is expected to develop a novel strategy for stem cell therapy that is clinically feasible and effective for brain and heart ischemia patients.
- We recently published the first report on the therapeutic effect of stem cell transplantation after
a severe transection injury of the sciatic nerve of rats (Cui et al., Stem Cells 2008). This work initiated a new stem cell therapy for the treatment of peripheral nerve injury. The information
from this investigation will also benefit and lead to research on spinal cord injury.
Other earlier studies:
- Regulation of the M-type potassium current (IM) by intracellular Ca2+ and its relationship to muscarine-induced IM suppression (Yu et al., J. Neurosci., 1996).
- Mediation of the Ca2+-dependent up-modulation of IM by the arachidonic acid pathway, lipoxygenases, and phosphatases (Yu, J. Physiol., 1995).
- Identification of the non-inactivating Na+ current in murine cortical neurons and the neuroprotective effect of Na+ channel blockers against excitotoxicity
(Lynch et al., J. Pharmacol. Exp. Ther., 1995)
- Acetylcholine (ACh) release (giant MEPPs or MEPCs) at mammalian neuromuscular junction
due to the extra loading of newly synthesized ACh and its regulation by choline uptake and
ACh synthesis (Ph.D. thesis; Yu & Van der Kloot. J. Physiol., 1991).
- ACh non-quantal release (ACh leak) may affect quantum size by changing ACh storage pool
in the nerve terminal (Ph.D. thesis; Yu & Van der Kloot. Neurosci. Letter., 1990).
- Mechanism of abnormal ACh release from presynaptic giant quanta induced by botulinum
toxin at neuromuscular junctions (Lupa & Yu. Pflugers Arch, 1986; Lupa et al., J. Physiol., 1986;
Tabti et al., Acta Physiol. Scand., 1986).
- Preventing transmission failure at mammalian neuromuscular junctions caused by irreversible cholinesterase inhibitors using aminoglycoside antibiotics and non-depolarizing muscle relaxants (Master degree thesis; Yu & Lui. Medical J. Chinese P.L.A., 1983; Yu & Lui. Acta Pharmacologica Sinica, 1985).
Our recent works have been presented in national and international meetings including the Annual
Meeting of Society for Neuroscience (1988 to 2008), International Conference of Apoptosis (2003),
the World Congress of Pharmaceutical Sciences (2004), and International Brain Conference (2007).
In addition, more than ten invited review articles or book chapters have been published or are in press.
Future plans and goal:
Our research interests are integrated into the framework of regulations of ionic homeostasis for cell differentiation, survival and regeneration under physiological and pathological conditions. A future area
of research is to delineate the mechanism and signal pathways that are involved in the ion channel and receptor regulation of pain sensation.
Personnel in the lab:
Adrian D. Sproul (MD/PhD student)
Xin Zhou (PhD student)
Kevin Francis (PhD student)
Past (last 5 years):
Postdoctoral Fellows, Research Fellow and Research Assistant Professor:
Xiangjun Zeng (2007- 2008) Current position: Assistant Professor at Capital University of Medical Sciences, Beijing, China
Paul Liu (2007- 2008) Current position: Physician at Zhejiang Hospital, Hangzhou, China
Xue Qing Wang, Ph.D. (2000 – 2004); Current position: postdoctoral fellow in Department of Neurobiology, the University of Chicago, Chicago, IL.
Toshihiro Takata (2001 –2004); Current position: Assistant Professor, Kobe University Graduate
School of Medicine, Kobe, Japan
Chuan-Shu Sun, M.D. (2004 – 2005). Postdoctoral Fellow; Current position: Research fellow at MUSC.
Yan Zhou, Ph.D. (2004 – 2005). Research Assistant Professor; Current position: Assistant Professor
Visiting Professor and Associate Professor:
Xiao Zhang, M.D., Ph.D. (2004). Visiting Associate Professor. Current position: Associate Professor, Division of Molecular Neuropharmacology, Karolinska Institutet, Stockholm, Sweden.
Jin-ping Li, M.D., Ph.D. (2004). Visiting Associate Professor. Current position: Associate Professor, Department of Biochemistry, Biomedical Center, Uppsala University, Sweden.
Aizhen Yang Hood (1999 – 2005)
Fan Fan (2004-2005)
Jun Hong Zu (2005-2008)