Pursuing Treatments for Deadly Neurodegenerative Disease

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

My research focused on progressive supranuclear palsy (PSP), a devastating neurodegenerative disease that affects patients' movement, behavior, and cognition. Currently, there is no therapy that can reverse or slow the rapid progression of the disorder, which leads to disability and eventual death.

Disease processes are extremely complex and difficult to study. In addition, progressive supranuclear palsy is a relatively rare condition. We were able to study samples of brain tissue, donated by patients who aim to contribute to research, in the Mayo Clinic Brain Bank, led by Dennis Dickson, M.D. Using the technique known as single-nucleus RNA sequencing, we measured the abundance of tens of thousands of RNA molecules in PSP brain tissue in order to find those that are perturbed and present at abnormal levels. Additionally, we checked if the abnormalities were consistent between PSP patients and existing models of PSP.

Our studies found that patients with PSP have abnormally high levels of RNA molecules from three genes, DDR2, KANK2 and STOM. Importantly, when we reduced the abnormally high levels of those molecules, we were able to improve some of the symptoms in models of PSP. Based on the results we reported in Nature Communications, we are now aiming to translate our basic science findings into a treatment by developing a drug that could potentially benefit patients.

What aspects of Mayo's culture and resources contributed to your research and helped you grow as a scientist?

Collaboration is a norm at Mayo Clinic. I received help from colleagues and leaders of other labs during my training. The Mayo Clinic Brain Bank is one of the largest brain banks in the United States. Dr. Dickson and his team made the deidentified brain tissue and high-quality neuropathological assessment information available to us. Additionally, our research relied on multi-omics data – a comprehensive quantification of all biomolecules, such as genes, RNA, and proteins – which, in part, was generated and processed by the Mayo Clinic Genome Analysis Core.

In addition to receiving help, we also give back to the scientific community by promoting open science data sharing. Using the innovative application of omics measures, the lab of my mentor, Dr. Ertekin-Taner, has made important strides in mapping changes in brain gene expression using brain tissue from PSP donors. With single-nucleus RNA sequencing, we were able to quantify tens of thousands of genes in every single cell. To make all the data open and accessible, I developed a user-friendly website where researchers around the world can access our data.

Importantly, our research program also received guidance from experts at Mayo Clinic Ventures about the steps needed for successful translation and commercialization of our discoveries. This was a unique experience that will certainly benefit my future career.

What's next?

My training in the Clinical and Translational Science track provided me with a clear understanding of the translational spectrum, in which discoveries in the lab lead to patient cures. I hope to become more involved in drug development. After graduating, I am staying at Mayo Clinic as a postdoctoral fellow to follow up on these interesting findings and hopefully develop a potential therapy for PSP.