Abstract

This is an application to become a Member of the NIEHS Toxicogenomics Research Consortium. The application originates from the synergistic fusion of two components of the Oregon Health Sciences University (OHSU), the resulting entity working in close cooperation with the Massachusetts General Hospital (MGH) at Harvard University. Leadership of this research program and the Toxicology Research Core Project (TRCP) is located in the OHSU Center for Research on Occupational and Environmental Toxicology (CROET), a dedicated research institute with strength in cellular, animal and human toxicology, with an emphasis on neurotoxicology. Co-leadership of this proposal is located in the nearby OHSU School of Medicine Department of Pediatrics which, together with participation from the Division of Medical Informatics and the Department of Medical and Molecular Genetics, brings strength in genomics, proteomics and bioinformatics, with emphasis on the developing brain and child health. Core Cl combines these components to support the toxicogenomics research needs of the TRCP and the Research Projects, PI-P3. Project 1 examines growth factor signaling in neural cells and its modulation by the neurotoxic anti-cancer drug taxol. Project 2 investigates early and late effects of genotoxic agents on neural development. Project 3, a subcontract with MGH, determines if neural and glial cells, as well as cells from different genetic strains, have overlapping or distinct patterns of toxicant-induced changes in gene expression that affect specific cellular functions, such as migration and division. The OHSU-MGH collaboration further strengthens this application by pooling our respective ongoing toxicogenomics studies and building an interdependent relationship for the benefit of the Consortium. Additionally, the participation in this proposal of scientific leaders of the NIEHS-funded Superfund Basic Research Center (SBRC) at OHSU (located in CROET) will ensure that the benefits of TRC membership are rapidly spread to other NIEHS-supported investigators at CROET and its collaborating SBRC institutions in the Pacific Northwest.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19ES011384-04
Application #
6787128
Study Section
Special Emphasis Panel (ZES1-LKB-E (RT))
Program Officer
Suk, William
Project Start
2001-09-30
Project End
2006-07-31
Budget Start
2004-08-01
Budget End
2005-07-31
Support Year
4
Fiscal Year
2004
Total Cost
$1,543,368
Indirect Cost

  Institution

Name
Oregon Health and Science University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239

  Publications

Kisby, Glen E; Spencer, Peter S (2011) Is neurodegenerative disease a long-latency response to early-life genotoxin exposure? Int J Environ Res Public Health 8:3889-921
Kisby, Glen E; Fry, Rebecca C; Lasarev, Michael R et al. (2011) The cycad genotoxin MAM modulates brain cellular pathways involved in neurodegenerative disease and cancer in a DNA damage-linked manner. PLoS One 6:e20911
Kisby, Glen; Palmer, Valerie; Lasarev, Mike et al. (2011) Does the cycad genotoxin MAM implicated in Guam ALS-PDC induce disease-relevant changes in mouse brain that includes olfaction? Commun Integr Biol 4:731-4
Tshala-Katumbay, Desire; Monterroso, Victor; Kayton, Robert et al. (2009) Probing mechanisms of axonopathy. Part II: Protein targets of 2,5-hexanedione, the neurotoxic metabolite of the aliphatic solvent n-hexane. Toxicol Sci 107:482-9
Dasari, Surendra; Wilmarth, Phillip A; Reddy, Ashok P et al. (2009) Quantification of isotopically overlapping deamidated and 18o-labeled peptides using isotopic envelope mixture modeling. J Proteome Res 8:1263-70
Tshala-Katumbay, Desire; Monterroso, Victor; Kayton, Robert et al. (2008) Probing mechanisms of axonopathy. Part I: Protein targets of 1,2-diacetylbenzene, the neurotoxic metabolite of aromatic solvent 1,2-diethylbenzene. Toxicol Sci 105:134-41
Beyer, Richard P; Fry, Rebecca C; Lasarev, Michael R et al. (2007) Multicenter study of acetaminophen hepatotoxicity reveals the importance of biological endpoints in genomic analyses. Toxicol Sci 99:326-37
Dasari, Surendra; Wilmarth, Phillip A; Rustvold, D Leif et al. (2007) Reliable detection of deamidated peptides from lens crystallin proteins using changes in reversed-phase elution times and parent ion masses. J Proteome Res 6:3819-26
Sabri, Mohammad I; Hashemi, Seyed B; Lasarev, Michael R et al. (2007) Axonopathy-inducing 1,2-diacetylbenzene forms adducts with motor and cytoskeletal proteins required for axonal transport. Neurochem Res 32:2152-9
Trimpin, Sarah; Deinzer, Max L (2007) Solvent-free MALDI-MS for the analysis of a membrane protein via the mini ball mill approach: case study of bacteriorhodopsin. Anal Chem 79:71-8

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