Pathology

Shu G. Chen, Ph.D.

Associate Professor

Mailing Address:
2103 Cornell Rd.
WRB 5533
Cleveland, OH 44106-7288

phone: (216) 368-8925
fax: (216) 368-0494
email: Shu.Chen@Case.edu

Biography
Dr. Shu Chen received his Ph.D. in Biochemical Pharmacology from the State University of New York at Buffalo in 1993. He came to Case as a Research Associate and moved on to be an Instructor and Assistant Professor in Case’s Institute of Pathology. Presently, Dr. Chen is an Associate Professor of Pathology (2002-) and an Associate Director of the National Prion Disease Pathology Surveillance Center (2003-).

Research
Alzheimer’s disease, Parkinson’s disease and prion disease are neurodegenerative diseases characterized by neuronal cell death and accumulation of insoluble protein aggregates. Prion disease is unique in that it consists of a group of heterogeneous brain disorders affecting both humans (such as Creutzfeldt- Jakob disease, CJD) and animals (such as mad cow disease). In humans, prion disease can be sporadic, inherited, or acquired by infection. The hallmark of prion disease is the presence of an abnormal isoform of prion protein (PrP) in the diseased brain. It is thought that the abnormal PrP is derived from the normal PrP that is also expressed in brain and throughout the body. Our primary interest is to characterize the chemical and structural abnormalities of PrP in the diseased state using a variety of biochemical and protein chemistry techniques. Our studies have shown that different conformational PrP variants are associated with distinct prion disease phenotypes, providing a useful insight into the mechanisms of pathogenesis. Our studies on other proteins implicated in Alzheimer’s disease and Parkinson’s disease have also unraveled chemical and structural changes in these proteins that suggest a common mechanism underlying neurodegeneration.

Our laboratory also serves as a facility for the National Prion Disease Surveillance Center and for Case Mass Spectrometry.

Publications
Parchi P, Zou W, 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 structural variations of the abnormal prion protein. Proc Natl Acad Sci USA 97, 10168-10172.

Lu K, Wang W, Xie Z, Wong BS, Li R, Petersen RB, Sy MS, Chen SG (2000). Expression and structural characterization of recombinant human doppel protein. B iochemistry 39, 13575-13583.

Gambetti P, Parchi P, Capellari S, Russo C, Tabaton M, Teller JK, Chen SG (2001). Mechanisms of phenotypic heterogeneity in prion, Alzheimer and other conformational diseases. J Alzheimer’s Disease 3, 87-95.

Zou W, Capellari S, Parchi P, 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.

Atwood CS, Perry G, Zeng H, Kato Y, Jones WD, Ling K-Q, Huang X, Moir RD, Wang D, Sayre LM, Smith MA, Chen SG Bush AI (2004). Copper mediates dityrosine crosslinking of Alzheimer’s amyloid- b. Biochemistry 43:560-568.

Zou W, Zheng J, Gray D, Gambetti P, Chen SG (2004). Antibody to DNA detects scrapie but not normal prion protein. Proc Natl Acad Sci USA 101, 1380-1385.

Narang, H, Dagdanova A , Xie Z, Yang Q, Chen SG (2005). Sensitive detection of prion protein in human urine. Exp. Med. Biol. 230:343-349.

Xie Z, O'Rourke KI, Dong Z, Jenny AL, Langenberg JA, Belay ED, Schonberger LB, Petersen RB, Zou W, Kong Q, Gambetti P, Chen SG (2005). Chronic wasting disease of elk and deer and Creutzfeldt-Jakob disease: Comparative analysis of the scrapie prion protein. J Biol Chem Dec 7; [Epub ahead of print].

Hatcher K, Harris C, Gambetti P, Chen SG (2005). Advances in Prion Disease Surveillance. Advances in Clinical Chemistry Vol. 41 (ed. Makowski GS). Elsevier, New York, NY, in press.

Guo L, Wang W, Chen SG (2006). Leucine-rich repeat kinase 2: relevance to Parkinson’s disease. Int. J. Biochem. Cell Biol (in press).