The primary focus of my research is prion diseases. The main objective is understanding the fine changes leading to the disease. The approach is multidisciplinary. My group analyzes the human prion disease and tries to establish accurate anatomo-clinical correlations. Special attention is devoted to understanding correlations between pathological changes, such as spongiosis, and the distribution, amount, and type of the abnormal prion protein present in the brain of affected individuals. For these studies we take advantage of the National Prion Disease Pathology Surveillance Center (NPDPSC). This center, which is located at CWRU, provides an invaluable source of cases of prion disease. We analyze in vitro the chemicophysical characteristics of the prion protein and the mechanisms of conversion of the normal to the abnormal prion protein conformer. Finally, we used transfected cells and transgenic animals to investigate in detail the various abnormalities of the prion protein metabolism related to the presence of mutations in the prion protein gene leading to disease.
Awards and Honors
Parchi P, Giese A, Carpellari S, Brown P, Schultz-Schaeffer W, Windl O, Zerr I, Budka H, Kopp N, Piccardo P, Poser S, Rojiani A, Streichemberger N, Julien J. Vital C, Ghetti B, Gambetti P, Kretzschmar H (1999). Classification of sporadic Creutzfeldt-Jacob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol 46, 224-233.
Gambetti P, Parchi P (1999). Insomnia in Prion Diseases: Sporadic and Familal. New Engl J Med 340, 1675- 1677.
Gambetti P, Goldfarb L, Gabizon R, Montagna P, Lugaresi E, Piccardo P, Petersen RB, Parchi P, Chen SG, Capellari S, Ghetti B (1999). "Inherited prion diseases." In: Prion Biology and Diseases, Cold Springs Harbor Laboratory Press, pp. 509-583.
Zanusso G, Petersen RB, Jin T, Kanoush R, Sharma Y, Ferrari S, Gambetti P, Singh N (1999). Proteasomal degradation and N-terminal protease resistance of the codon 145 mutant prion protein. J Biol Chem 274, 23396-23404.
Parchi P, Zou W, Wang W, Brown P, Capellari S, Ghetti B, Kopp N, Schulz-Schaeffer WJ, Kretzschmar HA, Ironside JW, Gambetti P, Chen SG (2000). Genetic influence on the structural variations of the abnormal prion protein. Proc Natl Acad Sci USA 97, 10168-10172.
Bütefisch CM, Gambetti P, Cervenakova L, Park KY, Hallett M, Goldfarb LG (2000). Inherited prion encephalopathy associated with the novel PRNP H187R mutation. A clinical study. Neurology 55, 517-522.
Russo C, Schettini G, Saido TC, Hulette C, Lippa C, Lannfelt L, Ghetti B, Gambetti P, Tabaton M, Teller JK (2000). Presenilin-1 mutations in Alzheimer's disease. Nature 405, 531-532.
Capellari S, Parchi P, Russo CM, Sanford J, Sy M-S, Gambetti P, Petersen RB (2000). Effect of the E200K mutation on prion protein metabolism: Comparative study of a cell model and human brain. Am J Pathol 157, 613-622.