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Wen-Quan Zou, M.D., Ph.D.Assistant ProfessorMailing Address: email: Wenquan.Zou@Case.edu |
Biography
Dr. Wen-Quan Zou received his medical degree from Jiangxi Medical College, his M.Sc. from Tongji
Medical University, and his Ph.D. from Shanghai Medical University. He has practiced Internal Medicine
and Nephrology for six years in China, as both a physician and an attending physician. His post-doctoral
work in neurodegenerative diseases, with a concentration in prion diseases, was done at the Institute
of Pathology at Case Western Reserve University and at the Centre for Research in Neurodegenerative
Diseases at the University of Toronto.
Research
Dr. Zou’s research focus is in the areas of protein aggregation in the conformational diseases especially
on the physiological and pathologic prion proteins (PrPC and PrPSc). The co-existence of the two molecules
in the central nervous system is a prerequisite for prion diseases, a group of fatal
transmissible neurodegenerative diseases such as Creutzfeldt-Jakob disease in human, scrapie in sheep
and goat, bovine spongiform encephalopathy in cattle, and chronic wasting disease in deer and elk.
His laboratory is the first to demonstrate that a small amount of insoluble aggregates and protease-
resistant conformers of PrP called silent prions is present in normal human brains (Yuan et al., 2006).
This finding is crucial to our understanding of the origin of prions in the spontaneous prion diseases,
a group of transmissible spongiform encephalopathies in humans and animals, for it may establish
the foundation upon which to explore the de novo generation of prions (Geoghegan et al., 2007; Brown,
2008). Zou’s lab subsequently reveled that silent prions are also present in uninfected cultured
neuronal cells (Yuan et al., 2008), a finding which demonstrated that cell models could be used to study
the molecular mechanism of silent prion formation. The discovery of silent prions may conceivably open a
new frontier for investigating the pathogenesis of prion diseases.
Publications
Parchi P, Zou WQ, Wang W, Brown P, Capellari S, Ghetti B, Kopp N, Schulz-Schaeffer WJ, Kretzschmar HA,
Head MW, Ironside JW, Gambetti P, Chen SG (2000). Genetic influence on the structural variations of
abnormal prion protein. Proc Natl Acad Sci USA 97, 10168-10172.
Zou WQ, Yang DS, Fraser PE, Cashman NR, Chakrabartty A (2001). All or none fibrillogenesis of a prion peptide. Eur J Biochem 268, 4885-4891.
Zou WQ, Cashman NR (2002). Acidic pH and detergents enhance in vitro conversion of human brain PrPC to a PrPSc-like form. J Biol Chem 277, 43942-43947.
Zou WQ, Capellari S, Parchi P, Sy M-S, Gambetti P, Chen SG (2003). Identification of novel proteinase K-resistant C-terminal fragments of PrP in Creutzfeldt-Jakob disease. J Biol Chem 278, 40429- 40436.
Paramithiotis E, Pinard M, Lawton T, LaBossiere S, Leathers V, Zou WQ, Estey L, Lamontagne J, Lehto MT, Kondejewski LH, Francoeur GP, Papadopoulos M, Haghighat A, Spatz SJ, Head M, Will R, Ironside J, O’Rourke K, Tonelli Q, Ledebur HC, Chakrabartty A, Cashman NR (2003). A prion protein epitope selective for the pathologically misfolded conformation. Nat Med 9, 893-899.
Zou WQ, Zheng J, Gray DM, Gambetti P, Chen, SG (2004). Antibody to DNA specifically detects scrapie but not normal prion protein. Proc Natl Acad Sci USA 101, 1380-1385.
Mishra RS, Basu S, Gu Y, Luo X, Zou WQ, Mishra R, Li R, Chen SG, Gambetti P, Fujioka H, Singh N (2004). Protease resistant human prion protein and ferritin are co-transported across Caco-2 epithelial cells: Implications for species barrier in prion uptake from the intestine. J Neurosci 24, 11280-11290.
Kong Q, Huang S, Zou WQ, Vanegas D, Wang M, Wu D, Yuan J, Bai H, Zheng M, Deng H, Chen K, Jenny AL, O’Rourke K, Belay ED, Schonberger LB, Petersen RB, Sy MS, Chen SG, Gambetti P (2005). Transmissibility of chronic wasting disease of elk to humans. J Neurosci 25, 7944-7949.
Zou WQ, Gambetti P (2005). From microbes to prions: The final proof of the prion hypothesis. Cell 121, 155-156.
Yuan J, Kinter M, McGeehan J, Perry G, Kneale G, Gambetti P, Zou WQ (2005). Concealment of epitope by reduction and alkylation in prion protein. Biochem Biophys Res Commun 326, 652-659.
Pastore M, Chin SS, Bell KL, Dong Z, Yang Q, Yang L, Yuan J, Chen SQ, Gambetti P, Zou WQ (2005). Creutzfeldt-Jakob disease (CJD) with a mutation at codon 148 of prion protein gene: relationship with sporadic CJD.Am J Pathol 167, 1818-1827.
Cali I, Capellari S, Yuan J, Al-Shekhlee A, Cohen ML, Xiao X, Moleres FJ, Parchi P, Zou WQ, Gambetti P (2006). Classification of Creutzfeldt-Jakob disease revisited. Brain 129, 2266-2277.
Yuan J, Xiao X, McGeehan J, Dong Z, Cali I, Fujioka H, Kong Q, Kneale G, Gambetti P, Zou WQ (2006). Insoluble aggregates and protease-resistant conformers of prion protein in uninfected human brains. J Biol Chem 281, 34848-34858.
Zou WQ (2007). Transmissible spongiform encephalopathy and beyond (e-Letter). Science.
Zou WQ, Gambetti P (2007). Prion: the chameleon protein. Cell Mol Life Sci 64:3266-3270.
Lefebvre-Roque M, Gilch S, Zou WQ, Feraudet C, Mourton-Gilles C, Sales N, Grassi J, Gambetti P, Baron T, Kremmer E, Schatzl H, Lasmezas CI (2007). Toxic effects of intracerebral PrP antibody administration during the course of BSE infection in mice. Prion 1:198-208.
Mehta LR, Huddleston BJ, Elaine J, Skalabrin EJ, Burns JB, Zou WQ, Gambetti P, Chin SS (2008). Sporadic Fatal Insomnia Masquerading as a Paraneoplastic Cerebellar Syndrome. Arch. Neurol. 65:971-973, 2008.
Yuan J, Dong Z, Guo JP, McGeehan J, Xiao X, Wang J, Cali I, McGeer PL, Cashman NR, Bessen R, Surewicz WK, Kneale G, Petersen RB, Gambetti P, Zou WQ (2008). Accessibility of a critical prion protein region involved in strain recognition and its implications for the early detection of prions. Cell. Mol. Life Sci. 65:631-643.
Kong Q, Zheng M, Casalong C, Qing L, Huang S, Chakraborty B, Wang P, Chen F, Cali I, Corona C, Martucci F, Iulini B, Acutis P, Wang L, Liang J, Wang M, Li X, Monaco S, Zanusso G, Zou WQ, Caramelli M, Gambetti P (2008). Evaluation of the human transmission risk of an atypical bovine spongiform encephalopathy prion strains. J. Virol. 82:3697-3701.
Gambetti P, Dong Z, Yuan J, Xiao X, Zheng M, Alshekhlee A, Castellani R, Cohen M, Barria MA, Romero DG, Belay ED, Schonberger LB, Marder K, Harris C, Burke JR, Montine T, Wisniewski T, Dickson DW, Soto C, Hulette CM, Mastrianni JA, Kong Q, Zou W. Q (2008). A novel human disease with abnormal prion protein sensitive to protease. Ann. Neurol. 63:697-708.
Maddox RA, Belay ED, Curns AT, Zou WQ, Nowicki S, Lembach RG, Geschwind MD, Haman A, Shinozaki N, Nakamura Y, Borer MK, Schonberger LB (2008). Creutzfeldt–Jakob disease in recipients of corneal transplants. Cornea 27:851-854.
Notari S, Strammiello R, Capellari S, Giese A, Cescatti M, Grassi J, Ghetti B, Langeveld JP, Zou WQ, Gambetti P, Kretzschmar HA, Parchi P (2008). Characterization of truncated forms of abnormal prion protein in Creutzfeldt-Jakob disease. J. Biol. Chem. 283:30557-30565.
Xiao, X., Miravalle, L., Yuan, J., McGeehan, J., Dong, Z., Wyza, R., MacLennan, G. T., Golichowski, A. M., Kneale, G., King, N., Kong, Q., Spina, S., Vidal, R., Ghetti, B., Roos, B., Gambetti, P. & Zou, W. Q. Failure to detect the presence of prions in the uterine and gestational tissues from a gravida with Creutzfeldt-Jakob disease. Am J Pathol. 174:1602-1608.
Zou WQ, Gambetti P (2009). Variant Creutzfeldt-Jakob disease: French versus British. Ann Neurol. 65:233-235.
Xiao X, Miravalle L, Yuan J, McGeehan J, Dong Z, Wyza R, MacLennan GT, Golichowski AM, Kneale G, King N, Kong Q, Spina S, Vidal R, Ghetti B, Roos K, Gambetti P, Zou WQ. Failure to detect the presence of prions in the uterine and gestational tissues from a Gravida with Creutzfeldt-Jakob disease. Am J Pathol. 2009, 174:1602-1608.