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Josephine Schamp

Mentor: Jonathan A. Doorn, PhD

Year Entered Into Program: 2011

PhD Institution: University of Iowa, 2017

Affiliations

  • Medicinal and Natural Products Chemistry

Research Description

Parkinson's disease (PD) is a common neurodegenerative disease where neuronal cell death occurs for the dopamine-containing neurons in the substantia nigra of the brain. Oxidative stress and the production of reactive oxygen species (ROS) and toxic dopamine metabolites are believed to contribute to this neurodegeneration. The metabolism of dopamine by monoamine oxidase produces a highly toxic intermediate, 3, 4- dihydroxyphenylacetaldehyde (DOPAL), and this metabolite is hypothesized to have a role in PD pathogenesis. Previous work has shown that DOPAL damages neurons through its interactions with proteins, specifically modification of Lys and Cys residues causing protein cross-linking. Oxidative stress was found to increase levels of DOPAL due to inhibition of its detoxication by carbonyl metabolizing enzymes. DOPAL also undergoes auto-oxidation to a harmful quinone and produces ROS. The reaction of DOPAL with proteins results in oxidative stress however the mechanism for ROS generation and the species of ROS has not been identified. My research goal is to investigate the production of ROS, ROS toxicity, and mechanism of etiology in regards to PD. 

Awards

  • Poster Award, Health Sciences Research Week, 2014
  • Winner, College of Pharmacy Graduate Student Poster Session, Carver College of Medicine Research Week, 2013
  • Fellowship appointment on the Pharmaceutical Sciences Training Program (NIH T32 GM067995), University of Iowa, 2013-2014
  • Institutional support on the Pharmaceutical Sciences Training Program (NIH T32 GM067995), University of Iowa, 2012-2013

Publications

  1. Bodle CR, Schamp JH, O'Brien JB, Hayes MP, Wu M, Doorn JA, Roman DL.: Screen Targeting Lung and Prostate Cancer Oncogene Identifies Novel Inhibitors of RGS17 and Problematic Chemical Substructures. SLAS Discov. 1:2472555217752301, 2018.  PMID: 29351497
  2. Bodle CR, Mackie DI, Hayes MP, Schamp JH, Miller MR, Henry MD, Doorn JA, Houtman JCD, James MA, Roman DL.:  Natural Products Discovered in a High-Throughput Screen Identified as Inhibitors of RGS17 and as Cytostatic and Cytotoxic Agents for Lung and Prostate Cancer Cell Lines. J Nat Prod. 80(7):1992-2000, 2017.  PMCID: PMC5567870
  3. Anderson DG, Florang VR, Schamp JH, Buettner GR and Doorn JA.:  Antioxidant-Mediated Modulation of Protein Reactivity for 3,4-Dihydroxyphenylacetaldehyde, a Toxic Dopamine Metabolite., Chemical research in  toxicology, 29:1098-107, 2016.  PMCID: PMC5248556
  4. Doorn JA, Florang VR, Schamp JH and Vanle BC.:  Aldehyde dehydrogenase inhibition generates a reactive dopamine metabolite autotoxic to dopamine neurons., Parkinsonism & related disorders, 20 Suppl 1:S73-5, 2014.  PMCID: PMC3932615