Office: (859) 257-4016
Fax: (859) 257-8382
Lab: (859) 257-4006
Chongsuk Ryou, Ph.D.
Doctoral Studies: Wayne State University.
Postdoctoral: University of California, San Francisco.
Prions are unconventional infectious pathogens that cause a variety of fatal neurodegenerative diseases in hosts. Prion diseases include Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and chronic wasting disease (CWD) in deer and elks. Although its unique property as a pathogen has been a subject of controversial debates since the discovery of the prion, the nature of the pathogen distinguishes prion from other conventional pathogens such as fungi, bacteria and viruses. To our current understanding, t he mode of prion propagation has become one of the paradigms that represent novel pathophysiological phenomena.
Prions are composed of protein termed PrP Sc that is devoid of nucleic acids. This disease-associated PrP Sc is a post-translationally misfolded isoform of PrP C encoded on PRNP gene locus and abundantly expressed in neurons. Despite the physiological role of PrP C has not been fully understood, expression of PrP C is tightly associated to the development of diseases. During prion pathogenesis, PrP Sc (disease-associated rogue PrP) recruits and converts PrP C (cellular PrP with normal physiological function) to form nascent PrP Sc. When PrP C is converted to PrP Sc, it undergoes a major biochemical alteration from an a-helical to a ß-sheet conformation. The switch of PrP C to PrP Sc requires the assistance of an auxiliary factor (provisionally designated protein X) that interacts with PrP C. Despite the numerous investigations searching for protein X, the molecular identity of protein X is still not evident.
Our long term goal of research is the understanding of the molecular mechanism of prion pathogenesis. This includes the understanding of molecular events during PrP C conversion to PrP Sc and biochemical alterations associated with prion infection and disease progression in the levels of cells and tissues.
Although recent experimental data advances our knowledge about the agent's ability to cross species barriers and options for detection and removal of the agent in addition to the nature of the agent, a majority of information about the molecular mechanism of prion propagation has not been clearly revealed. Thus, having the idea that protein X functions in the process of prion conversion, our primary interest and effort are focused on identifying protein X and understanding its interaction with PrP C for the conversion to PrP Sc.
Specifically, we have identified a group of candidate molecules for protein X using molecular biological means and biochemically characterized their binding properties to PrP C. With a reverse genetic approach, we verify their roles as protein X by testing whether the molecules functionally assist the molecular conversion of prion protein during pathogenesis. Other research projects are the investigations on 1) a physiological role of the interaction between PrP and its interacting proteins, 2) biochemical/cellular events that accompany with prion infection or result in disease progression, and 3) prion diagnostics and therapeutics.
Selected Recent Publications:
Mays CE, Yeom J, Kang H-E, Bian J, Khaychuk V, Kim Y, Bartz JC, Telling GC, Ryou C (2011) In vitro amplification of misfolded prion protein using lysate of cultured cells. PLoS ONE, 6:e18047. PDF
Ryou C, Titlow W, Mays CE, Bae Y, Kim S (2011) The suppression of prion propagation using poly-L-lysine by targeting plasminogen that stimulates prion protein conversion. Biomaterials, 32:3141-3149. ¶ PDF
¶ Public press-release for national and international news coverage. PDF
Lee H-J, Maeng K, Dang H-T, Kang G-J, Ryou C, Jung J, Kang H-K, Prchal J, Yoo E-S, Yoon D (2011) Anti-inflammatory effect of methyl dehydro-jasmonate is mediated by the NF-κB pathway. J Mol Med, 89:83-90. PDF
Mays CE, Ryou C (2011) Plasminogen: a cellular protein cofactor for PrPSc propagation. Prion, 5:22-27. PDF
Mays CE, Ryou C (2010) Plasminogen stimulates propagation of protease-resistant prion protein in vitro. FASEB J, 24:5102-5112. * PDF
*Public press-release for national and international news coverage, PDF
Lim Y-b, Mays CE, Kim Y, Titlow W, Ryou C (2010) The inhibition of prions through blocking prion conversion by permanently charged branched polyamines of low cytotoxicity. Biomaterials, 31:2025-2033. PDF
Kim Y, Han B, Titlow W, Mays CE, Kwon M, Ryou C (2009) Utility of RNAi-mediated prnp gene silencing in neuroblastoma cells permanently infected by prions: Potentials and limitations. Antiviral Res, 84:185-193 PDF
Mays CE, Titlow W, Seward T, Telling GC, Ryou C (2009) Enhancement of protein misfolding cyclic amplification by using concentrated cellular prion protein source. Biochem Biophys Res Commun, 338:306-310. PDF
Kim Y, Song J, Mays CE, Titlow W, Yoon D, Ryou C (2009) Changes in gene expression of kringle domain-containing proteins in murine brains and neuroblastoma cells infected by prions. Mol Cell Biochem, 328:177-182. PDF
Ryou C, Mays CE (2008) Prion propagation in vitro: are we there yet? Int J Med Sci, 5(6):347-353. PDF
Shin W, Lee B, Hong S, Ryou C, Kwon, M (2008) Cloning and expression of a prion protein (PrP) gene from Korean bovine (Bos taurus coreanae) and production of rabbit anti-bovine PrP antibody. Biotechnol Lett, 30:1705-1711. PDF
Mays CE, Kang H-E, Kim Y, Shim SH, Bang J-E, Woo H-J, Cho Y-H, Kim J-B, Ryou C (2008) CRBL cells: Establishment, characterization and susceptibility to prion infection. Brain Res, 1208:170-180. PDF
Ryou C (2007) Prions and prion diseases: Fundamentals and mechanistic details. J Microbiol Biotechnol, 17(7): 1059-1070. PDF
Yung L, Huang Y, Lessard P, Legname G, Lin ET, Baldwin MA, Prusiner SB, Ryou C, Guglielmo BJ (2004) Pharmacokinetics of quinacrine in the treatment of prion disease. BMC Infect Dis, 4:53. PDF
Ryou C, Legname G, Peretz D, Craig JC, Baldwin MA, Prusiner SB (2003) Differential inhibition of prion propagation by enantiomers of quinacrine. Lab Invest, 83(6): 837-843. PDF
Ryou C, Prusiner SB, Legname G (2003) Cooperative binding of dominant negative prion proteins to kringle domains. J Mol Biol, 329(2): 323-333. PDF
Bosque PJ, Ryou C, Telling G, Peretz D, Legname G, DeArmond S, Prusiner SB (2002) Prions in skeletal muscle. Proc Natl Acad Sci U. S. A., 99(6): 3812-3817. PDF
Book and Book Chapters
Ryou C (2011) Prion diseases, In: Encyclopedia of Life Science, John Wiley & Sons Inc., Hoboken, New Jersey, ISBN: 978-0-470-01590-2 (electronic version), DOI: 10.1002/9780470015902.a0000428.pub2). PDF
Ryou C, Mays CE (2010) Prions, In: Molecular aspects of infectious diseases, Ed. Saleh M, Nova Science Publisher, Hauppauge, NY. ISBN 978-1-61728-690-2
Ryou C (2010) Transmissible spongiform encephalopathy, In: Molecular aspects of infectious diseases, Ed. Saleh M, Nova Science Publisher, Hauppauge, NY. ISBN 978-1-61728-690-2
Kwon M, Ryou C (2004) Genetic Engineering: Principles and Practices, Academy Book Publishing Co., Seoul, Korea. ISBN 89-7616-284-6