Pesticide Toxicity in Multiple System Atrophy
Project Title
Pesticide Toxicity in Multiple System Atrophy
Faculty Mentor(s)
Project Description
Project Description:
Human exposure to pesticides have been shown to correlate with a higher incidence of chronic illnesses. Epidemiological data have established a strong relation between pesticide toxicity and neurodegenerative diseases, such as Parkinson's disease (PD). Mechanistic analysis suggests that bioaccumulation of pesticides in the brain can lead to generation of reactive oxidative species (ROS), protein aggregation, ionic imbalances, and mitochondrial dysfunction. Disruptions to these pathways can result in progressive loss of neurons, glia, and synapses can cause various cognitive, motor, and behavioral symptoms. Multiple system atrophy (MSA) is a progressive movement disorder characterized by autonomic failure, ataxia, and parkinsonism. Similar to PD, the pathological hallmark of MSA includes aggregates of misfolded α-synuclein, which have been shown to accelerate the fibrillation process. Disease progression is influenced by both environmental factors and genetics, including two specific mutations A53E and G51D. Using different oligodendroglial models, this project aims to understand if commonly used
Why is your research important?
Findings from this research project will provide greater insight into the public health risks posed by widespread use of agrochemicals and advocate for stricter regulations on the use of pesticides. Considering the extended availability of pesticides in the environment long after their initial use, this research will hopefully compel healthcare workers to advocate for increased preventative screening in at-risk populations.
What does the process of doing your research look like?
For this project, I culture and expose oligodendroglial cells to various pesticides. After that, I perform various cell-based bioassays to assess post-exposure cell viability and death, ROS production, mitochondrial dynamics, lipid peroxidation, and gene expression.
What knowledge has your research contributed to your field?
Genetic predisposition, specifically point mutations A53E and G51D in α-synuclein, can make an individual significantly more susceptible to neurodegeneration by specific pesticides. Specific mechanisms underlying this increased risk remain to be elucidated.
How did you get involved in research? What drove you to seek out research experiences in college?
I have always wanted to understand the mechanisms behind neurological disorders, so when I first started at Oberlin, I immediately reached out to Dr. Holly Shablack (psychology) and Dr. Monica Olszens (neuroscience) to get involved in their labs. This has allowed me to experience neuroscience research in different fields (cognitive vs molecular). I realized that my passion lies in understanding the specific molecular pathways that are compromised in disease states, and therefore started to get involved with Dr. Gunnar Kwakye's lab.
What is your favorite aspect of the research process?
I have really enjoyed the process of self-directed, data-driven scientific inquiry. I also enjoy methodologically trouble-shooting issues with my experiments, which has honed my critical thinking skills. I also appreciate the collaborative spirit in my lab.
How has working with your mentor impacted the development of your research project? How has it impacted you as a researcher?
Dr. Gunnar Kwakye is extremely meticulous, which has really helped me become a much better researcher during the short time I have worked with him. He has continuously supported me and other research students in all of our decisions, instilled in us a confidence and sense of self-worth that will be much needed beyond the confines of Oberlin.
How has the research you’ve conducted contributed to your professional or academic development?
Eventually, I want to become a physician-scientist focusing on brain cancer. This research experience has equipped me with various lab techniques that I will be using in my upcoming job as a research assistant in a new brain cancer research lab at CWRU / University Hospital.
What advice would you give to a younger student wanting to get involved in research in your field?
Never think that you're not ready to get involved in research!
Project Facts
Academic year:
2023–2024
Associated Departments:
Neuroscience, Chemistry and Biochemistry
Students
Shawn Ho ’24
fourth-year- Major(s): Neuroscience, Biochemistry