Analyzing Cell-to-Cell Communication in Disease

What drew you to science and what were the biomedical issues you addressed in your research?

I've always been curious about the natural world and, from a young age, loved exploring. Studying science appealed to me as a form of modern exploration. In college, I became interested in a career in biomedical science as a way of helping others.

My graduate research focused on an emerging area: the study of extracellular vesicles, also known as EVs, which have great potential to serve as diagnostic, prognostic and therapeutic tools to address disease. EVs are membrane-bound structures that are released by all types of cells. They serve as delivery vehicles, transporting cargo — proteins, lipids or RNA — to other cells. The cargo can vary if a cell is experiencing typical conditions or the duress of disease, so EVs can be useful tools for us to understand health and disease progression. Understanding the biology of EVs will be essential as researchers learn to use them in the treatment of disease.

My research investigated how EVs are released and how the cargo they transport is sorted into EVs. I studied two proteins: ALIX, which is known to be involved in EV formation; and HD-PTP, a related protein that had not yet been investigated in connection to this process. We found that genetically modifying cells so that they do not produce these proteins did not affect the number of small EVs released. However, knocking out the proteins resulted in EV cargo that was different from normal cells. In addition, the contents of the ALIX and HD-PTP knockouts were different from each other. I found that a cargo protein called syntenin was significantly reduced in EVs from ALIX knockout cells, and I used the ALIX-dependent cargo to understand how ALIX functions in EV release. In particular, I identified a portion of the ALIX protein that's necessary for EV formation. Our paper describing this work is currently in progress. The findings provide additional information about EV formation and further our understanding of cargo sorting.

What types of innovative technologies or approaches did you use in your research, and how did they further your project?

I used the gene editing technology CRISPR-Cas9 to delete the proteins associated with the machinery of EVs. The Mayo Clinic Cell Analysis Core was essential to my research. I had access to Nanoparticle Tracking Analysis to count and determine the size of EVs and state-of-the art software to perform 3-D analysis to quantify and measure the volume of different cellular compartments.

What aspects of Mayo’s culture and approach to training helped you grow as a scientist and thinker?

One great aspect of the graduate school is its unique funding model, in which students are supported by the school instead of by an individual lab. This allowed me to pursue a project that interested me and fueled my curiosity. Mayo has an immensely collaborative culture that permeates the faculty and students. Top researchers in the field were willing to help me. Mayo faculty have immense knowledge, and there's an awareness of patient experience and an interest in translating research to the bedside to benefit humankind.