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Research Interests:
Dr. Hamilton has research interests in the molecular biology of brain tumors, and neurodegenerative diseases such as Alzhemier's, Lewy Body Dementia, ALS and Parkinson's disease. The pediatric brain tumor research is conducted with Children's Hospital of Pittsburgh in collaboration with Dr. Ian Pollack, a pediatric neurosurgeon and the Children's Oncology Group (COG) and Pediatric Brain Tumor Consortium. As the diagnostic neuropathologist for the Neuropathology Core of the Alzheimer's Disease Research Consortium (ADRC) and Director of the Neuropathology Brain Bank, Dr. Hamilton also collaborates with numerous dementia researchers. Dr. Hamilton’s laboratory investigates aggregation and proteolysis of alpha-synuclein (the main protein component of Lewy bodies) using immunoblots of human tissue, in vitro studies using recombinant protein and an inducible cell system (Tet-off) with a neural cell line (B65).
Research Grants:
Pediatric Brain Tumor Clinical Trials Consortium: Novel Treatment Approaches for Pediatric Brain Tumors
Principal Investigator: Ian Pollack, M.D.
Co-Investigator: Ronald Hamilton, M.D.
Agency: NIH/NCI
Period: 7/1/99 – 6/30/04
% of Effort: 5%
Annual Direct Funding: $5448
This proposal details the extensive neuro-oncology resources available at the University of Pittsburgh Medical Center, University of Pittsburgh Cancer Institute and Children’s Hospital of Pittsburgh and indicates ways in which these activities can be integrated into ongoing clinical trials conducted by the Pediatric Brain Tumor Consortium. This provides support for banking of a limited number of brain tumor cases at Children’s Hospital of Pittsburgh.
Alzheimer Disease Research Center, Neuropathology Core
Principal Investigator: Steven DeKosky, M.D.
Co-Investigator: Ronald Hamilton, M.D.
Agency: NIH/NINDS
Period: 3/30/85 -4/30/05
% of Effort: 20%
Annual Direct Funding: $82,298
The major goal of the Alzheimer's Disease Research Center (ADRC) is to integrate, coordinate and support and foster research in Alzheimer Disease (AD) and aging. The three objectives of the Neuropathology Core are to (1) procure and bank brain from autopsies of ADRC patients and controls, (2) perform detailed neuropathologic analysis of all AD cases and (3) maintain well-catalogued brain bank. There is no overlap with the current project.
Morphologic/Neurochemical Correlates of Depression in AD
Principal Investigator: George Zubenko
Co-Investigator: Ronald Hamilton, M.D.
Agency: NIH
Period: 7/1/98-6/30/03
% of Effort: 2.5%
Annual Direct Funding: $2771
This research proposal describes a multi-site study (UCLA, University of Washington, Indiana University, Mt. Sinai, University of Pittsburgh) of the morphologic and neurochemical correlates of major depression in the context of AD. This prospective, clinicopathologic study will focus on three brainstem aminergic nuclei: the locus ceruleus, the substantia nigra, and the dorsal raphe nuclei. Coordinated efforts across the sites have resulted in the adoption of a common battery of clinical assessment tools, establishment of inter-rater and inter-site reliability, and standardization of autopsy and laboratory methods.
Molecular Markers of Prognosis in Pediatric Gliomas
Principal Investigator: Ian Pollack, M.D.
Co-Investigator: Ronald Hamilton, M.D.
Agency: NIH
Period: 7/1/98-6/30/02
% of Effort: 10%
Annual Direct Funding: $10,896
This study is an extension of preliminary work demonstrating that in pediatric high-grade gliomas, some markers such as MIB-1, p53 and bFGF are important predictors of prognosis. It will use materials collected from CCG participants across the nation and in addition begin exploring the use of other biological marker of prognosis in pediatric high-grade gliomas.
Selected Publications:
Hamilton RL. Lewy Bodies in Alzheimer’s Disease: an immunohistochemical study of 145 cases. Brain Pathol 10: 378-384, 2000.
Lopez OL, Hamilton RL, Becker JT, Wisniewski S, Kaufer DI, DeKosky ST. Severity of cognitive impairment and the clinical diagnosis of AD with Lewy bodies. Neurology 54:1780-1787, 2000
Sweet RA, Hamilton RL, Lopez OL, Klunk WE, Wisnieski SR, Kaufer DI, Healy MT, Dekosky ST. Psychotic symptoms in Alzheimer's Disease are not associated with more severe neuropathologic features. Internat Psychogeriatr 12: 547-558, 2000.
Pollack IF, Finkelstein SD, Woods J, Burnham J, Holmes EJ, Hamilton RL, Yates AJ, Boyett JM, Finlay J, Sposto R, and CCG. TP53 Mutations, Expression of p53 and Prognosis in Children with Malignant Gliomas. New England Journal of Medicine 346:420-427, 2002
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