Creating a New Strategy for Parkinson’s Disease

What issue did you address in your research, and what did your studies find?

My research tackles a major challenge in Parkinson's disease, addressing a misfolded protein known as alpha-synuclein that contributes to the progression of the disease. In patients, high levels of this protein can change shape and stick together, forming harmful clusters that contribute to the symptoms of the disease.

I developed a way to dial down how much of this protein is made in the brain. I used a gene-regulation tool called CRISPR interference (CRISPRi), which can reduce protein production without permanently altering DNA. In combination with advanced brain-targeted delivery methods, this targeted approach uses a virus called adeno-associated virus as a transport mechanism to enable the CRISPRi tool to reach and treat neurons throughout the brain.

Our research team found in preclinical models that it's possible to prevent alpha-synuclein from forming the aggregates that are associated with the early stages of Parkinson's disease. We also used human neurons derived from patients' induced pluripotent stem cells to validate these findings, an exciting step toward the development of a therapy that could one day halt the progression of Parkinson's disease.

What opportunities at Mayo Clinic have helped you further your growth as a scientist and your career goals?

While I have gained strong technical and scientific expertise, the most valuable part of my training has been learning how to approach complex problems collaboratively. I have developed the ability to ask thoughtful questions and seek out different perspectives and skills that I will carry into the next stage of my career.

Mayo Clinic also provided opportunities to engage with the broader scientific community. I presented my research at international conferences in Vienna and Cambridge, UK, as well as at national meetings, which strengthened my ability to communicate complex ideas and connect with others in the field.

Equally rewarding has been the leadership role I cultivated as a mentor to high school, undergraduate and post-baccalaureate students in the Science Program for the Advancement of Research Knowledge (SPARK), the Summer Undergraduate Research Fellowship (SURF) Program, and the Post-baccalaureate Research Education Program (PREP).

Guiding these aspiring researchers through their own scientific journeys has been incredibly rewarding. For instance, mentoring a SPARK student on a traumatic brain injury project culminated in a co-authored publication. Supporting these mentees as they transition into medical and graduate school has been one of the most meaningful aspects of my training.

What's next?

Following graduation, I will continue as a postdoctoral fellow in the Department of Neuroscience in Jacksonville, focusing on overcoming the translational barriers to bringing our research closer to patient therapies.

This article was written by Lizz Cervantes, a Ph.D. candidate in Clinical and Translational Science at Mayo Clinic Graduate School of Biomedical Sciences.