Exploring a New Frontier in Cell Communication: A Q&A with the Burnette Lab on Blebbisomes

Since its publication on February 21, 2025, the Burnette Lab’s article detailing the discovery of blebbisomes—a newly identified class of extracellular vesicles—has received over 44,000 Article Accesses, a remarkable benchmark for scientific reach and engagement. This visibility is due in part to Vanderbilt University’s new open access agreement with Springer Nature, announced earlier this year. “This collaboration not only strengthens Vanderbilt’s reputation but will aid in attracting top faculty, students and partnerships to the university,” said University Librarian Jon Shaw.

The blebbisome study, published in Nature Cell Biology, exemplifies the impact of this open access model—advancing fundamental discovery, encouraging broad readership, and sparking new scientific conversations worldwide.

Cover of Nature Cell Biology
Cover of the Nature Cell Biology (Zach Sanchez)

In the Q&A below, Dylan Burnette, associate professor of cell and developmental biology, shares insights into the team’s discovery, the methods that made it possible, and the biological and translational promise of these massive, motile vesicles.

What issue or problem does your research address?
We were interested in how cells communicate through extracellular vesicles, especially ones that hadn’t been well-studied. We discovered a completely new class of EVs called blebbisomes, which are huge and surprisingly active. Our research focused on defining what these are, how they form, and what roles they might play in normal biology and diseases like cancer.

 What was unique about your approach?
Our approach combined live-cell imaging, super-resolution microscopy, and correlative electron microscopy to watch blebbisomes form and move—something that hadn’t been done before. That effort was led by graduate student Zach Sanchez, one of the co-first authors.

This level of visualization let us study their structure and function in ways traditional techniques couldn’t. The project also relied on a close collaboration with Bob Coffey’s lab at VUMC—particularly co-first author Dennis Jeppesen. Vanderbilt’s advanced imaging and proteomics core facilities were essential and made this kind of interdisciplinary work possible.

What are your top three findings?

  1. We discovered a new kind of extracellular vesicle—blebbisomes—that are much larger and more complex than previously known.
  2. Blebbisomes are motile and packed with organelles, including functioning mitochondria, making them behave almost like mini cells.
  3. They carry and release cargo such as immune checkpoint proteins (e.g., PD-L1 and CD47), which could help cancer cells evade immune detection.

What do you hope will happen with these results in the short term?

We hope other researchers will start looking for blebbisomes in different tissues, diseases, and biological contexts. We also want to better understand how they form, what regulates them, and whether they play roles in communication or immune response.

What’s your long-term or clinical vision for this research?
We think blebbisomes could be used as therapeutic delivery vehicles—like naturally occurring biological drones. They might also serve as biomarkers or therapeutic targets, especially if they’re aiding immune evasion in cancer. Ultimately, understanding them could unlock new ways to diagnose or treat disease.

What small but important elements helped make this work possible?
Transmitted light microscopy—a strength of the Burnette Lab—was critical. It’s how we first identified blebbisomes. Purification techniques developed by Dennis Jeppesen in the Coffey Lab enabled everything that followed, including proteomics and sharing samples for validation. Zach Sanchez, a graduate student and co-first author, drove the imaging work that brought the story together.

What core facilities supported this research?
We used several Vanderbilt core facilities:

  • Cell Imaging Shared Resource
  • Nikon Center of Excellence
  • Mass Spectrometry Research Center Proteomics Core

Their expertise was essential for the imaging and proteomics work.

Where is this research heading next?
We’re now studying how blebbisomes behave in living organisms, especially whether they contribute to immune evasion in cancer. We’re also testing whether they can be engineered to deliver therapeutic cargo. I’m personally focused on developing the imaging tools needed to track and manipulate blebbisomes in real time, and we’re working with collaborators to explore their role in disease models.