Wen-Quan Zou, M.D., Ph.D.

Associate Professor

Mailing Address:
Institute of Pathology
2085 Adelbert Road, Room 403
Cleveland, OH 44106

phone: (216) 368-8993
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 Nanchang and Shanghai, China, as both a physician and an attending physician, respectively. 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 University of Toronto. Currently, Dr. Zou is an Associate Professor of Pathology with tenure and Associate Director of the National Prion Disease Pathology Surveillance Center at Case Western Reserve University School of Medicine.

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) in prion diseases (PrD) as well as on neurotoxic amyloid β (Aβ) in Alzheimer disease (AD). The co-existence of PrPC and PrPSc in the central nervous system is a prerequisite for PrD, a group of fatal transmissible neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD) in humans, 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 small amounts of insoluble aggregates and protease-resistant conformers of PrP called insoluble PrPC (iPrPC) are present in normal human brains (Yuan et al., 2006). The discovery of this new isoform of PrPC may conceivably open a new frontier for investigating the pathogenesis of PrD. For instance, his laboratory also observed that a new protease-resistant PrPSc species with an immunoreactivity behavior and fragmentation similar to iPrPC is present in an atypical sporadic human prion disease termed variably protease-sensitive prionopathy and a familial prion disease (Zou et al., 2010; Zou et al., 2011; Xiao et al., 2013; Zou et al., 2013) and a relative early-stage of a subset sporadic prion disease (Yuan et al., 2008). Remarkably, the Zou laboratory revealed for the first time that iPrPC is the major PrP species that interacts with Aβ in AD and that human PrP exhibits two types of Aβ-binding sites on in terms of its specificity for Aβ42 (Zou et al., 2011). Currently, the Zou laboratory is studying the role of iPrPC in the pathogenesis of both PrD and AD using patient-specific iPSCs-derived neurons as well as in the ischemia reperfusion injury of tissues and organs.

Publications

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. Zou WQ, Gambetti P (2005). From microbes to prions: The final proof of the prion hypothesis. Cell 121, 155-156.
  6. 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.
  7. 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.
  8. Zou WQ (2007). Transmissible spongiform encephalopathy and beyond (e-Letter). Science http://www.sciencemag.org/content/308/5727/1420.long/reply#sci_el_10316.
  9. 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.
  10. 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.
  11. 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.
  12. Zou WQ, Puoti G, Xiao X, Yuan J, Qing L, Cali I, Shimoji M, Langeveld JP, Castellani R, Notari S, Crain B, Schmidt RE, Geschwind M, Dearmond SJ, Cairns NJ, Dickson D, Honig L, Torres JM, Mastrianni J, Capellari S, Giaccone G, Belay ED, Schonberger LB, Cohen M, Perry G, Kong Q, Parchi P, Tagliavini F, Gambetti P (2010). Variably protease-sensitive prionopathy: a new sporadic disease of the prion protein. Ann. Neurol. 68:162-172.
  13. Zou WQ, Langeveld J, Xiao X, Chen S, McGeer PL, Yuan J, Payne MC, Kang HE, McGeehan J, Sy MS, Greenspan NS, Kaplan D, Wang GX, Parchi P, Hoover E, Kneale G, Telling G, Surewicz WK, Kong Q, Guo JP (2010). PrP conformational transitions alter species preference of a PrP-specific antibody. J. Biol. Chem. 285:13874-13884.
  14. Fernandez-Funez P, Zhang Y, Casas-Tinto S, Xiao X, Zou WQ, Rincon-Limas DE (2010). Sequence-dependent prion protein misfolding and neurotoxicity. J. Biol. Chem.285:36897-36908.
  15. Zou WQ, Xiao X, Yuan J, Puoti G, Fujioka H, Wang X, Richardson S, Zhou X, Zou R, Li S, Zhu X, McGeer PL, McGeehan J, Kneale G, Rincon-Limas DE, Fernandez-Funez P, Lee HG, Smith MA, Petersen RB, Guo JP (2011). Amyloid-beta42 interacts mainly with insoluble prion protein in the Alzheimer brain. J. Biol. Chem. 286:15095-15105.
  16. Zhou X, Bi H, Wong J, Shimoji M, Yuan J, Xiao X, and Zou WQ (2011). Alkylating antitumor drug mechlorethamine conceals a structured PrP domain and inhibits in vitro prion amplification by. J Toxicol Environ Health A. 74:1493-1503.
  17. Zou WQ, Zhou X, Yuan J, Xiao X (2011). Insoluble cellular prion protein and its association with prion and Alzheimer diseases. Prion 5:172-178.
  18. Zou RS, Fujioka H, Guo JP, Xiao X, Shimoji M, Kong C, Chen C, Tasnadi M, Voma C, Yuan J, Moudjou M, Laude H, Petersen RB, Zou WQ (2011). Characterization of spontaneously generated prion-like conformers in cultured cells. Aging (Albany NY) 3:968-984.
  19. Kudo W, Lee HP, Zou WQ, Wang X, Perry G, Zhu X, Smith MA, Petersen RB, Lee HG (2012). Cellular prion protein is essential for oligomeric amyloid-β-induced neuronal cell death. Hum Mol Genet. 21:1138-1144.
  20. Luo JJ, Truant AL, Kong Q, Zou WQ (2012). Sporadic fatal insomnia with clinical, laboratory, and genetic findings. J Clin Neurosci. 19:1188-1192.
  21. Xiao X, Yuan J, Zou WQ (2012). Isolation of soluble and insoluble PrP oligomers in the normal human brain. J Vis Exp. (68), e3788 10.3791/3788.
  22. Xiao X, Cali I, Dong Z, Puoti G, Yuan J, Qing L, Wang H, Kong Q, Gambetti P, Zou WQ (2013). Protease-sensitive prions with 144-bp insertion mutations. Aging (Albany NY) 5:155-173.
  23. Xiao X, Yuan J, Haïk S, Cali I, Zhan Y, Moudjou M, Li B, Laplanche JL, Laude H, Langeveld J, Gambetti P, Kitamoto T, Kong Q, Brandel JP, Cobb BA, Petersen RB, Zou WQ (2013). Glycoform-selective prion formation in sporadic and familial forms of prion disease. PLoS ONE 8:e58786.
  24. Pirisinu L, Nonno R, Esposito E, Benestad SL, Gambetti P, Agrimi U, Zou WQ (2013). Small ruminant nor98 prions share biochemical features with human Gerstmann-Sträussler-Scheinker disease and variably protease-sensitive prionopathy. PLoS ONE 8:e66405.
  25. Zou WQ, Gambetti P, Xiao X, Yuan J, Langeveld J, Pirisinu L (2013). Prions in Variably Protease-Sensitive Prionopathy: An Update. Pathogens 2:457-471.
  26. Yuan J, Zhan YA, Abskharon R, Xiao X, Martinez MC, Zhou X, Kneale G, Miko J, Lehmann S, Surewicz WK, Castilla J, Steyaert J, Zhang S, Kong Q, Petersen RB, Wohlkonig A, Zou WQ (2013). Recombinant Human Prion Protein Inhibits Prion Propagation in vitro. Sci Rep. 3:2911; DOI:10.1038/srep02911.

Book
Zou WQ and Gambetti P (Eds), Prions and Diseases: Volume 1, Physiology and Pathophysiology; Volume 2, Animals, Humans, and the Environment, Springer, New York, USA, 2013.