Neurodegenerative diseases are most notably characterized by the intra and extra-cellular accumulation of misfolded proteins in neurons. Alzheimer’s disease (AD) is specifically caused by the buildup of neurofibrillary tangles and neuritic plaques in the brain. Typically, these plaques form in regions of the brain that control memory formation and recall such as the hippocampus and cortex. Similarly, Parkinson’s disease (PD) - a neurodegenerative disease caused by the death of neurons responsible for dopamine production - has a profound effect on an individual’s ability to control their coordination and movement. Both of these diseases affect millions of Americans each year, hence there is an urgent need for new therapies that can remedy affected cells and prevent future degeneration.
This summer I had the opportunity to work on a project in Dr. Xiaolu Yang’s lab in the Abramson Family Cancer Research Institute in the Perelman School of Medicine. During my time in the lab I worked directly with my mentor Dr. Dilshan Harischandra aiding in his research project focused on the cellular mechanisms involved in neurodegenerative diseases. The goal of this project was to test the therapeutic potential of the TRIM family of proteins against AD and PD. We have previously shown the ability of TRIM11 to degrade misfolded proteins in-vitro.
In the current study, we further validated this phenomenon in animal models of AD and PD. Specifically, we used intracranial stereotaxic injection to deliver our protein of interest via adeno associated viral therapy to brain regions typically affected by these diseases. Following the injections, we then conducted a series of behavioral and biochemical tests to gauge the effects that TRIM11 had on the mice versus control mice. Our initial results show a positive impact of TRIM11 delivery on remediation of the cellular pathology associated with neurodegeneration.
Working on this project has allowed me to grow as a researcher and I have learned several new skills. I was tasked with maintaining a large mouse colony, which includes setting up breeding pairs, weaning pups, ensuring the mice were healthy, especially after the stereotaxic surgery. Additionally, I developed skills related to the following techniques: Western blotting, Polymerase Chain Reaction (PCR), immunohistochemistry staining, recombinant protein purification, and mammalian tissue culture. Furthermore, I am going to start my own project in the fall involving the in vitro side of TRIM11’s effects on cells expressing plaque formation. Moreover, I learned how to keep a proper lab notebook and get a feel for what a career in research would actually entail. This experience has provided invaluable insight into biomedical research and has allowed me to grow both as a student and as an employee.