Meet Nydia Chang, a graduate student in Brian Daniels' lab received a National Institutes of Health Ruth L. Kirschstein NRSA Predoctoral Fellowship (F31) to study the roles for astrocytic RIPK3 signaling in Parkinson's disease pathogenesis.
How did you become interested in science?
It was very interesting because it wasn't through a science class. It was actually through a history project I did my junior year of high school. We had to do research on the Cold War, and I was assigned to President Ronald Reagan. I was fascinated by his strategic plans dealing with the political situation. I then read about his diagnosis of Alzheimer's disease and became curious about it and from there, began to read about some of the basic concepts of neuroscience. It was pretty amazing. It was an interesting experience, because the more I read about it, the more excited I got. I thought the brain was one of the most mysterious organs in the human body, and I still think of it this way!
I remember Rutgers-Robert Wood Johnson Medical School had an annual event for high school students, called the 'Brain Bee Competition'. It was like jeopardy but for neuroscience. To prepare for the competition, we had to read a manual of materials on basic neuroscience, and that was how I started learning more about it. I still remember the cover of the manual was a girl and her brain was portrayed in a very intricate way, like her skull was transparent and her brain was glowing some blue light or something. I knew I was going to do research on neurodegenerative disease soon after, even before I entered my senior year of high school.
Did you do any research as an undergraduate?
I did my undergraduate research with Dr. Crockett at the Robert Wood Johnson Medical School in the Dept. of Neuroscience and Cell Biology. Dr. Crockett studies both spinal cord injury and traumatic brain injury (TBI), and my projects were mainly on TBI. Dr. Crockett's lab is where I was more sure that I wanted to pursue research. I learned important skills that would later help me in graduate school. It was also where I acquired skills for mouse work, and survival surgery (this is surgery to generate the model for TBI where we keep the mice for a few days before euthanizing them). I really liked being in the lab because doing lab work took my mind off whatever stress I was going through.
What are you researching now?
Parkinson’s disease is the second most common neurodegenerative disease of global concern, with total economic burden of $52 billion per year in the United States. Approximately 60,000 people per year are diagnosed in the country and more than 10 million people worldwide are living with this disease. The major symptoms of Parkinson’s disease include tremors, impaired balance, muscle rigidity, and loss of spontaneous movement. Parkinson’s disease pathology is characterized by progressive death of dopamine-producing cells in the midbrain of the central nervous system (CNS), known as dopaminergic neurons, and reduction of dopamine production in the brain region striatum. These two brain regions make up the nigrostriatal pathway that functions to influence voluntary movement.
Emerging evidence suggests that an overactive immune response in the CNS may contribute to the progression of many neurodegenerative diseases, including Parkinson’s disease. Astrocytes are an multi-functional cell type that not only regulate the nutrient uptake by neuron and fuel neuronal metabolism, but also response to inflammatory environment following disease, infection, or injury and become an active state known as reactive astrocyte. Numerous studies have now revealed that reactive astrocytes play key roles in contributing to neurotoxicity and eventually neuronal death. However, the mechanisms that drive homeostatic astrocytes to become reactive remain understudied.
My project at the Daniels Lab is investigates the molecule, receptor-interacting serine/threonine protein kinase-3 (RIPK3), in activating inflammatory responses in the astrocytes and promoting astrocyte activation in the context of Parkinson’s disease. I am also interested in examining whether the process of neurodegeneration generate further inflammatory cues that feedforward astrocyte activation. In addition, as motor functions are highly impacted in Parkinson’s disease patients, we will be assessing behavior performance for our mouse models in collaboration with the graduate student, Marialaina Nissenbaum in Alexander Kusnecov Lab at Rutgers Department of Psychology.
We have used a combination of mouse genetic model targeting astrocyte-specific RIPK3 and cell culture systems to answer these questions. The neurotoxin MPTP is used to cause degeneration specific to dopaminergic neurons and Parkinsonian pathology. With both transcriptional and microscopy approaches, I have examined for dopaminergic neuron degeneration and astrocyte activation. Under the F31 fellowship, my goals for training include expanding my knowledge and skills in studying neurodegenerative disease, acquiring proficiency in bioinformatics and rodent behavior study. Overall, my research project at the Daniels Lab has great potential to provide knowledge in the field of astrocyte biology and inform future researchers in designing immunotherapy, in the context of neurodegenerative diseases.