First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Ashley Peterson is first author on ‘ Neutrophil motility is regulated by both cell intrinsic and endothelial cell ARPC1B’, published in JCS. Ashley conducted the research described in this article while a graduate research assistant (PhD student) in Anna Huttenlocher's lab at the University of Wisconsin-Madison, USA. She is currently searching for jobs in pharmaceutical/biotech industry. Her research interests are in using in vitro and microfluidics systems to model human disease for drug discovery and preclinical testing.

Ashley Peterson

How would you explain the main findings of your paper in lay terms?

Actinopathies are a broad class of diseases that affect the actin cytoskeleton, resulting in a spectrum of dysregulated functions in the immune system. This immune dysregulation is largely studied in the context of motile immune cells such as neutrophils. Variants in the actin-binding protein ARPC1B lead to excessive neutrophil inflammation around blood vessels and tissue damage. Our study used two neutrophil cell lines and an endothelial-based blood-vessel-on-a-chip model to show that both neutrophils and endothelial cells drive the excessive inflammation. Endothelial cells deficient in ARPC1B are sufficient to alter the motility of wild-type neutrophils in our blood-vessel-on-a-chip system. This work shows that in this disease model, endothelial cells are the main drivers of inflammation, and that the actin cytoskeleton regulates inflammation via mechanisms beyond consequential motility defects in immune cells.

Were there any specific challenges associated with this project? If so, how did you overcome them?

Learning how to use the blood-vessel-on-a-chip model was technically challenging, and using different stem cell-derived endothelial cells introduced unexpected variability into our methods. However, by taking some careful notes and tweaking our methods, we were able to consistently generate blood vessels for our study of multicellular interactions. I'm hopeful that the work we did to validate our endothelial model will be helpful to researchers who might want to use this model in the future.

When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?

When using the blood vessel-on-a-chip model, we were surprised to find that although ARPC1B-knockout (KO) and wild-type vessels had similar barrier functions, fewer neutrophils were able to pass through the KO vessel. We suspected that the KO vessel lumens might be leakier in response to bacteria, because actin is important for maintaining cell–cell junctions in endothelial cells. However, this wasn't the case. It actually seemed as if primary neutrophils were attracted to the endothelial cells in the KO vessels. This early experiment validated our disease model for ARPC1B deficiency, as this finding was reminiscent of the vasculitis seen in individuals with ARPC1B actinopathy.

Why did you choose Journal of Cell Science for your paper?

We wanted to submit to Journal of Cell Science because of its great reputation for publishing cell biology papers, and because it is not-for-profit. The short report format was ideal for this work, because we were able to publish our findings quickly. We experienced a really fast turnaround time for both the review and publication processes.

Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?

I've really appreciated having Prof. Anna Huttenlocher as my research mentor. Her enthusiasm for science and research is contagious and I've been so grateful for her support in my work. I've also been lucky to work with some amazing colleagues in the Huttenlocher lab, including a few of our former post-docs, Veronika Miskolci and Briana Rocha-Gregg. Both Veronika and Briana were always supportive of me and my growth, and I was inspired by their methodical approach to research and the kindness in all their feedback and interactions.

What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?

I've always been fascinated by the natural world and have had a love of biology for as long as I remember. I wanted to go to graduate school because I wanted to continue to explore my love for immunology and work towards building knowledge and research that could lead to new drugs and therapies for people living with different diseases.

Who are your role models in science? Why?

I've always looked up to my supervisor Anna for her success in research as well as for her support for all the members of her lab. I've also met many people at the University of Wisconsin-Madison that I look up to, mostly for their research acumen but also for the support they give to mentees.

What's next for you?

I'm currently seeking scientist roles in the pharmaceutical industry. I've really loved my time in academia and working in Anna's lab, but I'm really excited by the idea of using the skills I've gained to support a company in bringing new pharmaceuticals to the market in order to help people living with immune diseases.

Tell us something interesting about yourself that wouldn't be on your CV

When I'm not working, I love watching any show on Bravo – it's a lovely way to turn off my brain a little and unwind.

D. J.
Neutrophil motility is regulated by both cell intrinsic and endothelial cell ARPC1B
J. Cell Sci.