ABSTRACT
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. Konstantin Stoletov is first author on ‘ Intravital imaging of Wnt/β-catenin and ATF2-dependent signalling pathways during tumour cell invasion and metastasis’, published in JCS. Konstantin is a Research Associate in the lab of John Lewis at Department of Oncology, University of Alberta, Canada, investigating intravital imaging of cancer metastasis.
Konstantin Stoletov
How would you explain the main findings of your paper in lay terms?
Canonical Wnt signaling (cWnt) and ATF2 signaling pathways are some of the most studied in biology, yet their activation patterns are very hard to study in live tissues and live organisms. Luckily in our group, we have a unique system where we can image cancer cell movement (invasion) in the live tissue (chick CAM). Our model allows us to see, in real time, where and when during the various steps of metastatic cascade these pathways are active. We use fluorescent reporters that light up if these pathways are active. Besides obtaining visually beautiful data, our results are also very counterintuitive. We found that during active stages of cancer invasion cWnt pathway is downregulated, while the ATF2 pathway is hyperactive. This is almost opposite to what we expected and unexpected is always exciting! Not only this will be interesting to the broad Wnt research community but also might lead to better design of anticancer therapies since one would know what to target and what to not target to stop the cancer cells spreading.
Were there any specific challenges associated with this project? If so, how did you overcome them?
Intravital imaging is challenging in general due to live tissues or animals moving and breathing; blood vessels shift their positions due to the heartbeat. Patience is the best way to overcome these challenges. I often spend a night next to the microscope in my sleeping bag to make sure that I will be there to re-align the device setup if the whole imaging field shifts yet again.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
When we first saw the canonical Wnt pathway activity pattern during the primary tumor cell invasion, that was clearly our ‘eureka’ moment. We found that green cells (canonical Wnt high) don't move much! We saw that cancer cells with high Wnt canonical activity were not invading much, they tended to be in the main tumor mass and not interacting well with the vasculature. It was quite opposite to what we expected; this is when we decided to pursue this project with full effort.
Why did you choose Journal of Cell Science for your paper?
JCS publishes good research quality papers and specifically it often publishes great imaging manuscripts. I often visit the JCS website just to look at something ‘cool’ imaging wise. These two factors made our choice simple since our work is all about good intravital imaging.
Wnt canonical (red, mCherry) and ATF2 (green, GFP) pathway reporter activity during cancer cell invasion. Vasculature (white) is labeled with Lectin-649.
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
My collaboration with Dr Robert Kypta was quite an experience. Our lab is proficient in imaging, yet we are new to the ‘Wnt field’. So, I had to run all the results and ideas by Robert and his graduate student Saray Sanchez. The learning curve was quite steep, but it paid off.
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?
When I was 5 or 6 years old, I found a page from a biology textbook on the street. It had images and some names of beetles that live in Siberia (this is where I am from). I was so fascinated by the colors and Latin names that I decided to study them… I never managed to learn Latin or learn the names of all those beetles, but I became a biologist.
Who are your role models in science? Why?
I don't think I have real life ones. Again, when I was a kid, I liked Jules Verne books. Captain Nemo? Does he count as a scientist?
What's next for you?
Finding my own independent position, ideally in Canada, because this country is so good! Yes, it is challenging but I need to keep trying and I will prevail.
Tell us something interesting about yourself that wouldn't be on your CV
I am a very active climber. If I am not at work, I am in the mountains working on new climbs or mountain running. The biggest/hardest sport climbing area that is closest to my hometown, Edmonton is called Little Russia (one can guess why). I wish I could put it on my CV.
Konstantin Stoletov's contact details: Department of Oncology University of Alberta Room 5126, Katz Group Centre 114th Street and 87th Avenue Edmonton, Alberta T6G 2E1 Canada. E-mail: kstoletov@gmail.com
