Dr. Xiongwei Zhu received his B.S. in 1995 and M.S. in 1998 from the Department of Biochemistry at Wuhan University in China. He received his Ph.D. in 2002 from the Department of Pathology at Case Western Reserve University. He was a postdoctoral fellow and instructor in pathology until he became Assistant Professor in 2004. Dr. Zhu is the recipient of several awards including the International Junior Investigator Award from International College of Geriatric Psychoneuropharmacology and the Vector Laboratories Young Investigator Award from the International Congress of Histochemistry & Cytochemistry.
Dr. Zhu's research focuses on the neurodegenerative mechanisms underlying Alzheimer disease and other neurodegenerative diseases. Alzheimer's disease is a major public health problem because it has a huge impact on individuals, families and society and it has attracted increasing public attention as the population ages which highlights the urgency to understand and treat this disease effectively. Dr. Zhu and his colleagues have demonstrated that both oxidative stress and cell cycle-related abnormalities are among the earliest contributors to the disease. The major hypothesis being pursued is that while either oxidative stress or abnormalities in mitotic signalling can independently serve as initiators, both processes are necessary to propagate disease pathogenesis and progression (Two Hit Hypothesis, Zhu et al., 2004).
Dr. Zhu's specific projects include:
1. Mitochondrial abnormality and its contribution to oxidative stress
2. Oxidative stress signaling
3. Mitogenic signaling and inappropriate cell cycle re-entry
Zhu X, Raina AK, Rottkamp CA, Aliev G, Perry G, Boux H, Smith MA (2001). Activation and redistribution of c-Jun N-terminal kinase/stress activated protein kinase in degenerating neurons in Alzheimer's disease. J Neurochem 76, 435-441.
Zhou F*, Zhu X*, Castellani RJ, Stimmelmayr R, Perry G, Smith MA, Drew KL (2001). Hibernation, a model of neuroprotection. Am J Pathol 158, 2145-2151. (* equal contribution).
Perry G, Zhu X, Smith MA (2001). Do neurons have a choice in death? Am J Pathol 158, 1-2.
Zhu X, Perry G, Raina AK, Smith MA (2002). The role of mitogen-activated protein kinase pathways in Alzheimer disease. NeuroSignals 11, 270-281.
Hartzler AW, Zhu X, Siedlak SL, Castellani RJ, Avila A, Perry G, Smith MA (2002). The p38 pathway is activated in Pick disease and progressive supranuclear palsy: a mechanistic link between mitogenic pathways, oxidative stress, and tau. Neurobiol Aging 23, 855-859.
Zhou F, Braddock JF, Hu Y, Zhu X, Castellani RJ, Smith M, Drew K (2002). Microbial origin of glutamate, hibernation and tissue trauma: an in vivo microdialysis study. J Neurosci Meth 119, 121-128.
Cash AD, Aliev G, Siedlak SL, Nunomura A, Fujioka H, Zhu X, Vinters HV, Tabaton M, Johnson AD, Paula- Barbosa M, Avila J, Jones PK, Castellani RJ, Smith MA, Perry G (2003). Microtubule reduction in Alzheimer disease and aging is independent of tau filament formation. Am J Pathol 162, 1623-1627.
Zhu X, Perry G, Smith MA (2003). The JNK pathway in ALS. Redox Report 8, 129-33.
Zhu X, Ogawa O, Wang Y, Perry G, Smith MA (2003). JKK1, an upstream activator of JNK/SAPK, is activated in Alzheimer disease. J Neurochem 85, 87-93.
Zhu X, Sun Z, Lee HG, Siedlak SL, Perry G, Smith MA (2003). Distribution, levels and activation of MEK1 in Alzheimer disease. J Neurochem 86, 136-142.
Zhu X, Raina AK, Shimohama S, Perry G, Smith MA (2004). Bcl-w plays a neuroprotective role in Alzheimer disease. J Neurochem 1233-1240.
Ma YL, Rice ME, Chao LM, Riveral PM, Zhao HW, Ross AP, Zhu X, Smith MA, Drew KL (2004). Ascorbate distribution during hibernation: independence of ascorbate redox state. Free Radic Biol Med 37, 511-514.
Zhu X, Raina AK, Lee HG, Smith MA, Perry G (2004). Oxidative stress signaling in Alzheimer disease. Brain Res 1000, 32-39.
Zhu X, Raina AK, Perry G, Smith MA (2004). Alzheimer disease: the two hit hypothesis. Lancet Neurol 3, 219-226.
Webber, K.M., Smith, M.A., Lee, H.G., Harris, P.L.R., Moreira, P.I., Perry, G. and Zhu, X. (2005). Mitogen- and stress-activated protein kinase 1: convergence of the ERK and p38 pathways in Alzheimer disease. J. Neurosci. Res., 79, 554-560.
Zhu, X., Smith, M.A., Perry, G., Wang, Y., Rivera, P.M., Ross, A.P., Zhao, H.W., LaManna, J.C. and Drew, K.L. (2005). The MAPKs are differentially modulated in AGS during hibernation. J. Neurosci. Res., 80, 862- 868.
Honda, K., Smith, M.A., Zhu X., Baus, D., Merrick, W.C., Tartakoff, A.M., Hattier, T., Harris, P.L., Siedlak, S.L., Fujioka, H., Liu, Q., Moreira, P.I., Miller, F., Nunomura, A., Shimohama, S. and Perry, G. (2005). Ribosomal RNA in Alzheimer disease is oxidized by bound redox-active iron. J. Biol. Chem., 280, 20978-86.
Zhu, X., Lee, H.G., Casadesus, G., Avila, J., Drew, K., Perry, G. and Smith, M.A. (2005). Oxidative imbalance in Alzheimer disease. Mol. Neurobiol., 31:205-17.
Zhu X, Moreira PI, Smith MA, Perry G. (2005). Alzheimer's disease: an intracellular movement disorder? Trends Mol Med. 11:391-3.
Zhu, X., Mei, M., Lee, H.G., Wang, Y., Perry, G. and Smith, M.A. (2005). p38 activation mediates amyloid-? cytotoxicity. Neurochem. Res., 30:791-796.
Ma, Y., Zhu, X., Rivera, P., Toien, O., Barnes, B.M., LaManna, J., Smith, M.A. and Drew, K. (2005). Endogenous protection against hypoxia and reperfusion during hibernation and arousal in arctic ground squirrels. Am J Physiol Regul Integr Comp Physiol. 289(5):R1297-306.