Rachel Crawford

Mentor: Jonathan A. Doorn, PhD

Year Entered Into Program: 2017

Terminal Degree(s) Received and Year: PhD 2023

Research Description

Identification and quantification of biogenic aldehyde conjugates in neuronal cells

Parkinson’s Disease (PD) is a degenerative disease of the central nervous system characterized by bradykinesia and tremors with a loss of dopaminergic cells in the brain, particularly in the substantia nigra. Dopamine, an important neurotransmitter, is metabolized to 3,4-dihydroxyphenylacetaldehyde (DOPAL) by monoamine oxidase and further biotransformed to an acid or alcohol product. DOPAL is a highly reactive metabolite that is toxic to dopaminergic cells, where it is produced. Under normal conditions, DOPAL is further metabolized to the nontoxic acid or alcohol products, however, under pathological conditions or following insult, DOPAL can increase to harmful levels. DOPAL and other biogenic aldehydes are hypothesized as chemical triggers of disease (catecholaldehyde hypothesis) that cause cell death, protein aggregation and oxidative stress. Identifying targets of and quantifying dopamine metabolite protein adducts is valuable because of their implication in PD and may yield elucidation of biomarkers for earlier diagnosis or mechanistic targets for drug discovery. Such findings may yield novel biotechnology to diagnose disease (e.g., PD) earlier and development of therapeutics which address the pathogenic process. My current project is the identification of viable biomarkers for determination and quantification of DOPAL conjugates in neuronal cells using near-infrared fluorescence.

Awards

  • Fellowship appointment on the Pharmacological Sciences Training Program (NIH T32 GM067795), University of Iowa, 2018-2020
  • MNPC fellowship appointment, University of Iowa, academic year 2017-2018

Publications

  1. Hayes MP, O'Brien JB, Crawford RA, Fowler CA, Yu L, Doorn JA, Roman DL. Fragment-Based Nuclear Magnetic Resonance Screen against a Regulator of G Protein Signaling Identifies a Binding "Hot Spot". Chembiochem. 2021 Jan 21. doi: 10.1002/cbic.202000740. Epub ahead of print. PMID: 33480159
  2. Crawford, R.A., Bowman, K.R., Cagle, B.S., and Doorn, J.A. (2020) The inhibition of glutathione S-transferase by dopamine and its metabolites. Neurotoxicology. (Submitted)
  3. Cagle, B.S., Crawford, R.A., Doorn, J.A. Aberrant dopamine metabolism as a focal point in the mechanism of environmental contaminant-induced dopaminergic dysfunction. Molecular and Integrated Toxicology.  (Submitted)
  4. Bell, K., Lansakara, T., Crawford, R., Monroe, B.T., Tivanski, A., Salem, A., Stevens, L.:  Mechanical cues protect against ROS-mediated silica nanoparticle toxicity in SH-SY5Y neuroblastoma. Toxicology in Vitro. 70:105031, 2020.  PMID: 33075489  doi:10.1016/j.tiv.2020.105031. Online ahead of print.
  5. Cagle, B.S., Crawford, R.A. and Doorn, J.A.: Biogenic Aldehyde-Mediated Mechanisms of Toxicity in Neurodegenerative Disease. Current opinion in toxicology 13:16-21, 2019.  PMCID: PMC6625780

 

 

Research