First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Sara Sannino is the first author on ‘ Compensatory increases of select proteostasis networks after Hsp70 inhibition in cancer cells’, published in Journal of Cell Science. Sara is a postdoctoral fellow in the lab of Jeffrey L. Brodsky at The University of Pittsburgh, Pennsylvania, investigating the role of protein folding and degradation pathways in cancer survival.
How would you explain the main findings of your paper in lay terms?
To efficiently divide, survive under extreme conditions and invade other organs, cancer cells need to modulate multiple pathways. Among them, protein folding and degradation machineries are the most important ones, as they ensure the production of functional proteins that will guide cancer cell survival, even upon cancer drug treatments. There is much evidence of tumor relapse or resistance to conventional therapies. Thus, to study what the compensatory mechanisms are that may play a crucial role in cancer cell survival, even after therapeutic treatments, will be important to develop efficient strategies to treat cancer patients. We focus our attention on a chaperone family, called Hsp70, known to be upregulated in a variety of cancers and whose activity was demonstrated to be important for rhabdomyosarcoma cancer cell survival in previous work by the Brodsky lab. We discovered that cancer cells that are insensitive to Hsp70 inhibition tend to upregulate protein degradation pathways to get rid of the accumulating unfolded proteins. In particular, inhibition of autophagy degradation was able to sensitize cells resistant to Hsp70 inhibition. These findings identify autophagy as the responsible pathway for Hsp70 drug resistance and will impact the development of therapeutic small-molecule strategies in cancers.
Were there any specific challenges associated with this project? If so, how did you overcome them?
I really like challenging projects, setting up new assays or finding new important links between different pathways. In general, working at the edge of several fields, like cancer biology, cell death, molecular biology and cell biology, will help you obtain a broad idea of science and it will give you the opportunity to learn many important things. This project was performed in a lab that mainly studies proteasomal degradation and the endoplasmic reticulum associate degradation (ERAD) pathway. Thus, when I hypothesized that autophagy was playing a role in our system, I needed to set up assays, and select and test reagents under different conditions by myself. It was fundamental for me to read as much as possible and learn from published literature, as well as to participate in cancer meetings like the AACR, which helped me to get in contact with people in the cancer and autophagy fields to ask for suggestions or learn important tricks that I needed to use to finalize my project.
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
“In science we need to work hard but we also need to be stimulated to be more productive and creative.”
I have to admit that I was a lucky person because I always found mentors that were able to teach me something important during my scientific career. No one is perfect, but you can learn what aspect of your mentor's behavior you want to take with you and improve and what you want to avoid. This will help the formation of your scientific personality and help you to deal with uncomfortable situations. During this project, Jeffrey L. Brodsky was my mentor, and I really enjoyed chatting and discussing several aspects of this project with him. He always has good suggestions and he has been helping me to improve my writing skills a lot. He helped me find the right contact to perform assays for which our lab was not equipped. I really enjoy working with smart and positive people. It makes me super enthusiastic about what I am doing and it helps me to come up with new ideas. In science we need to work hard but we also need to be stimulated to be more productive and creative.
“…what I am obtaining with my hard work matters to someone else!”
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 have always been a person who loved learning about how things work and why they are like that. This attitude makes a child or teenager less popular in our society but, in a way, you will be different and special. That is what everybody should be. A different entity with its own special skills who likes to interact with other people and the surrounding environment to create a great connecting network. Thinking that my work can potentially help other people develop novel cancer treatment strategies or inspire other scientists to figure out what is going on in their model system makes me enthusiastic about the job I am doing. It means that what I am obtaining with my hard work matters to someone else! I often look at myself as a police detective on a crime scene and I need to find what is responsible for my experimental outcome.
Tell us something interesting about yourself that wouldn't be on your CV
I have a profound sense of justice and I do my best to help friends and colleagues day by day. When experiments are not working or I am stressed or too busy, having the right music playlist is essential for me. In particular, Christmas songs help me calm down and put me in a happy festive mood when I am stressed or anxious, while classic rock is my go-to type of music when I have a lot of work to do.
Sara Sannino's contact details: Department of Biological Sciences, University of Pittsburgh, A321 Langley Hall, Pittsburgh, PA 15260, USA.