Jonathan Weerakkody, PhD, Receives Patterson Trust Mentored Research Award

I joined Yale three years ago in the Department of Pathology, where I began working on extracellular vesicles, tiny vesicles released by cells that carry RNA and protein cargo.

These were once thought of as “cellular trash,” but we now think of them more like little packages of mail that cells use to communicate with each other. If we can isolate these vesicles and open them up, we can catch a snapshot of what the cell is experiencing at that moment. Early on, I helped develop a new method to isolate these vesicles more efficiently, which has been patented through Yale Ventures.

I moved to the Department of Neurology one year ago to work with David Pitt, MD, a multiple sclerosis clinician and director of the National MS Brain Bank. That transition allowed me to bring my extracellular vesicles expertise directly into translational MS research, connecting what we see in the lab to real patient care.

In our current work, we focus on extracellular vesicles that come specifically from one cell type, astrocytes, a supportive brain cell that becomes highly reactive in MS. From just 0.5 mL of blood, we can isolate astrocyte-derived extracellular vesicles and analyze their RNA cargo, giving us a window into inflammation and damage occurring in the brain.

By combining these extracellular vesicles signals with clinical data and analyzing them using machine learning and deep learning models, we aim not only to understand MS, but also to predict disease course months or even years before symptoms worsen. This lays the groundwork for blood tests that could guide treatment decisions, making it easier to give the right patient the right therapy at the right time, and to avoid both over-treatment and delayed treatment.

The core MS progression biomarker work supported by this award is primarily carried out within the Pitt Lab in Neurology and is scientifically strengthened by external collaborations.

We work with colleagues in Turku, Finland, and with a biomedical company, using samples from large MS clinical trials. These partnerships give us access to well-characterized patient cohorts and imaging data, which are essential for testing whether our extracellular vesicles-based biomarkers truly predict disease activity and treatment response in real-world settings.

Within Yale, my extracellular vesicles research is closely connected to a growing community of investigators interested in these therapeutics and diagnostics. I co-host and help organize a monthly Yale EV Club that brings together like-minded faculty and trainees from the Departments of Cell Biology, Pathology, Obstetrics & Gynecology, Neurology, and Biomedical Engineering.

While this group is not a formal, co-led project, it creates a space where we share methods, ideas, and data around extracellular vesicle-based therapeutics and diagnostics, using extracellular vesicles both to detect disease and to deliver targeted treatments. That crosstalk within YSM directly shapes how we think about applying extracellular vesicle tools to MS and other neurological disorders. Readers can contact me if they are interested in learning more.

The most rewarding part of my work is the possibility that a simple blood test could significantly improve MS patient care. Right now, patients and clinicians often must make major treatment decisions without clear tools to predict who is likely to worsen and who is likely to remain stable. Knowing that our research might someday spare patients from unnecessary side effects, or prevent irreversible disability by identifying high-risk patients earlier, is incredibly motivating.

The Patterson Mentored Research Award is transformative for this effort. It gives us the time, resources, and mentorship to move from a “promising signal” in the lab to a rigorously validated, first-in-class biomarker for MS progression, a test that can truly move from bench to bedside and guide real-world treatment decisions.

Yale has world-class core facilities and expertise in genomics, imaging, and computational biology. This means that in a single place we can isolate extracellular vesicles, measure thousands of molecules inside them, and then apply state-of-the-art data science and deep learning tools to find patterns that may predict MS progression.

The culture here is also highly collaborative. Through initiatives like the Yale EV Club, I can sit in the same room with engineers, immunologists, neurologists, and pathologists who are all looking at extracellular vesicles from different angles. That kind of environment makes it much easier to turn an idea into a concrete experiment and eventually a potential clinical tool.

I hope future MS researchers will take the idea of cell-type specific extracellular vesicles in blood and keep pushing it forward, both as biomarkers and as therapeutic tools. On the diagnostic side, I’d like to see our astrocyte extracellular vesicle signatures expanded to larger, more diverse MS populations and turned into simple tests that can be used in routine clinic visits, not only for MS but also for other brain disorders such as amyotrophic lateral sclerosis, Alzheimer’s disease, stroke, autism, and age-related brain decline. In parallel, as the field continues to develop engineered extracellular vesicle and extracellular vesicle-mimicking particles that can carry drugs with a built-in “address label” for specific brain cells, I hope our work will help define the right targets, the right cell types, and the right timing, laying the groundwork for truly personalized, extracellular vesicle-guided therapies for people living with MS and other neurodegenerative diseases.