Neuropathology Core C The Neuropathology Core (Core C) of the Johns Hopkins Udall Parkinson's Disease Research Center has three overarching goals. The first is to conduct postmortem neuropathological assessments in subjects from the Clinical Core and to distribute autopsy brain tissues for research to Projects 1, 2 &4 and the Proteomic Core. The second is to obtain a comprehensive genetic profile of all the postmortem tissues available in the Udall Center collection. The third is to provide support for the morphological evaluation of genetically engineered mouse models by investigators in Projects 1, 2 &4.
The specific aims of Core C are as follows: (1) to arrange and perform neuropathological autopsies of cases of Parkinson's disease (PD) and Lewy body disease (LBD), and control subjects followed by the Clinical Core, and to formulate pathological diagnoses; (2) to accession, prepare, catalog, and assist in the analysis of human postmortem tissues from cases of PD/LBD and related disorders, as well as age-matched and also younger controls for studies proposed in Projects 1, 2 &4 and the Proteomic Core;(3) to characterize the molecular genetic profiles of PD/LBD postmortem tissues available in the BRC through a collaboration with the Laboratory of Neurogenetics at NIA (A. Singleton, Ph.D.);and (4) to use CLARITY technology for preparation of mouse brain tissues in support of studies delineated in Projects 1, 2 &4. Despite recent advances in neuroimaging postmortem brain examination remains indispensable. For accurate diagnosis of PD (Parkinson's disease) and LBD (Lewy body disease) in our experience, ~20% of cases clinically diagnosed as PD have other etiologies, and >30% of the cases have coexisting morbidities. Moreover, since autopsies are the essential source of tissues for studying molecular/biochemical abnormalities of the human brain associated with PD/LBD, a thorough pathological characterization is important before tissues can be used in studies proposed in Projects 1, 2 &4 and by the Proteomic Core. Core C is expanding its postmortem tissue collection to include a large number of specimens from younger subjects (16 to 65 years) suitable to examine the very early stages of PD/LBD pathology and its pathogenesis. These tissues are accessioned through collaboration with the Lieber Institute for Developmental Disorders at Johns Hopkins. Finally, by using CLARITY, a state-of-the-art morphological technique implemented by Core C, investigators in Projects 1, 2 &4 will be able to produce translucent preparations of whole mouse brains that allow interrogation of molecular events not only of single neuronal populations but of networks relevant to PD and LBD.

Public Health Relevance

The Morris Udall Center for Parkinson's Disease Research of the Johns Hopkins University is an integrated program aimed at finding improved treatments for patients with Parkinson's disease and Lewy body diseases. Complimentary activities within the center include clinical and basic research studies that incorporate state- of-the art methodologies, and contribute significantly to national programs. Specifically, Core C will conduct neuropathological autopsies, formulate diagnoses, and prepare and distribute post-mortem brain tissues for research to investigators at JHU Udall Center and extramurally, collaborate on the genetic profiling of a large collection of post-mortem PD/LBD tissues accrued over the last fifteen years, and provide support to basic research projects on state-of-the-art morphological approaches.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
2P50NS038377-16
Application #
8882843
Study Section
Special Emphasis Panel (ZNS1-SRB-J (07))
Project Start
Project End
Budget Start
2014-09-30
Budget End
2015-07-31
Support Year
16
Fiscal Year
2014
Total Cost
$283,500
Indirect Cost
$108,500
Name
Johns Hopkins University
Department
Type
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Martin, Ian; Kim, Jungwoo Wren; Dawson, Valina L et al. (2014) LRRK2 pathobiology in Parkinson's disease. J Neurochem 131:554-65
Dawson, Ted M; Dawson, Valina L (2014) Parkin plays a role in sporadic Parkinson's disease. Neurodegener Dis 13:69-71
Lee, Yun-Il; Giovinazzo, Daniel; Kang, Ho Chul et al. (2014) Protein microarray characterization of the S-nitrosoproteome. Mol Cell Proteomics 13:63-72
Siuda, Joanna; Jasinska-Myga, Barbara; Boczarska-Jedynak, Magdalena et al. (2014) Early-onset Parkinson's disease due to PINK1 p.Q456X mutation--clinical and functional study. Parkinsonism Relat Disord 20:1274-8
Fatokun, Amos A; Dawson, Valina L; Dawson, Ted M (2014) Parthanatos: mitochondrial-linked mechanisms and therapeutic opportunities. Br J Pharmacol 171:2000-16
Stafa, Klodjan; Tsika, Elpida; Moser, Roger et al. (2014) Functional interaction of Parkinson's disease-associated LRRK2 with members of the dynamin GTPase superfamily. Hum Mol Genet 23:2055-77
Martin, Ian; Kim, Jungwoo Wren; Lee, Byoung Dae et al. (2014) Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson's disease. Cell 157:472-85
Tsika, Elpida; Glauser, Liliane; Moser, Roger et al. (2014) Parkinson's disease-linked mutations in VPS35 induce dopaminergic neurodegeneration. Hum Mol Genet 23:4621-38
Pirooznia, Sheila K; Dawson, Valina L; Dawson, Ted M (2014) Motor neuron death in ALS: programmed by astrocytes? Neuron 81:961-3
Lasagna-Reeves, Cristian A; Sengupta, Urmi; Castillo-Carranza, Diana et al. (2014) The formation of tau pore-like structures is prevalent and cell specific: possible implications for the disease phenotypes. Acta Neuropathol Commun 2:56

Showing the most recent 10 out of 141 publications