First person – Kelsey Prince and Samantha Bunner Free

Kelsey Prince

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

K.P.: The nucleus of a cell is like its instruction manual: it guides the functions of your cells and body, and helps to prevent disease. In many different diseases, such as cancer, heart disease or Alzheimer's disease, a common abnormality called a nuclear bleb − which looks like a hernia on what is normally supposed to be an oval-shaped nucleus − appears. Detecting these blebs can aid in diagnosing disease; for example, a pap smear involves looking for nuclear blebs in cervical cells. Our work shows that DNA density is a more reliable measure of nuclear blebs than a nuclear lamina protein called lamin B1, because lamin B1 levels can change drastically.

S.B.: Our genetic material is protected in the nucleus and perturbations to the nucleus are found in many human diseases. Abnormal nuclear shape is a useful diagnostic tool to screen for cancers, such as cervical cancer, and can indicate the aggressiveness of disease. A nuclear bleb is a herniation of the nucleus, which is often accompanied by dysfunction, such as DNA damage. Although previous literature suggests that blebs are nuclear domains lacking lamin B, we find that this characteristic is cell type specific. We show that a more universal method to detect blebs is by looking at DNA density, given that the DNA in a bleb is always less dense than that in the rest of the nuclear body. By better understanding nuclear bleb composition, we hope to improve its utility as a marker of disease.

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

K.P.: A major challenge was organizing a team of 16 undergraduate students to produce publication-quality data in less than one academic semester. Many of the students were new to microscopy, so we had a large hurdle of teaching everyone before we could begin our research. With the guidance of a dedicated professor, teaching assistant and lab technicians, along with teamwork and collective focus, we successfully met this challenge.

S.B.: I also agree − optimizing the project for a semester-long honors biology course was a challenge. We needed careful planning and communication. As undergraduate students, we had a wide range of research experiences, which offered many perspectives and skillsets. I enjoyed the class because we each shared and learned something new in the process. As a member of a microscopy lab, I helped my classmates with timelapse imaging of cells, and my peers taught me new skills in using analysis software. Together, our shared ideas and skills made a great paper!

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

K.P.: My eureka moment came from analyzing a timelapse of lymph node carcinoma of the prostate (LNCaP) cancer cells. I noticed that these cells rarely ruptured even when blebbed, unlike mouse embryonic fibroblast (MEF) cells, which rupture ∼90% of the time when they are blebbed. LNCaP cells also have much higher and more constant levels of Lamin B1 than our MEF cells lines, which led us to believe that rupture was an important factor in whether cells were Lamin B1 positive or not.

S.B.: Something that stuck with me in this project was my experience during the writing of the manuscript. I think that it is very easy for young scientists like myself to have imposter syndrome, but when I saw the experiments I performed and suggestions I made in the paper, I was very excited! It was a very positive experience to see a paper be produced from an inclusive group of people.

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

K.P.: We chose JCS because we believed it would provide a fair review and help strengthen our story. Initially, we aimed for publication in a Special Issue but decided to take more time to expand on our work and publish alongside our collaborators.

S.B.: We were happy to choose JCS for their trusted peer review process and Open Access model. The Stephens lab has previously chosen to submit papers to JCS and we are happy to do so again in the future!

Samantha Bunner

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

K.P.: Yes! Dr Rosa Moscarella, a genetics professor at the University of Massachusetts (UMass) Amherst, mentored me as an undergraduate student, sparking my passion for biology and encouraging me to get involved in research on campus. My PI, Dr Stephens, has also been invaluable in both my undergraduate and graduate studies. He has helped me to grow as an independent researcher, especially in microscopy and cellular biology.

S.B.: I am very thankful for my mentors at UMass Amherst: Dr Abigail Jensen, who encouraged me to continue research and reach my career goals, Dr Rosa Moscarella, who co-sponsored my undergraduate honours thesis and helped me grow as a scientist and Dr Stephens, who introduced me to research and supported me academically.

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?

K.P.: When going into college, I initially considered a career in medicine, but lab courses sparked a passion for experimental design and a desire to gain a deeper understanding of biology. After joining a research lab as an undergraduate, I knew that I wanted to continue my career in research. I made the decision to continue my academic career as a graduate student in the same lab I worked in during my undergrad. Staying here has allowed me to dive deeper into my project and work on publishing for the lab.

S.B.: My main motivation is my sister, who has Aicardi syndrome, a rare neurodevelopmental disorder with no known cause. As an undergraduate, I found it very interesting that beyond our genetic code, there are many levels of organization that protect and regulate our genome. By investigating this genomic organization, I hope to gain a new perspective to better understand its implications in diseases such as Aicardi syndrome.

Who are your role models in science? Why?

K.P.: My former lab managers are big role models for me. Their dedication to our lab made me want to be a better researcher. They inspired me to work harder and fostered a positive and supportive community. I strive to be as dedicated to my work and make as positive of an impact on future researchers as they had for me.

S.B.: I have had many great experiences with other researchers, both at UMass and the NIH. My former PI Dr Stephens set an example as a science investigator and by sharing the four tenets he lives by: prioritize, communicate, think, repeat. At the NIH, I am supported by a great lab that continues to make me a better researcher. Finally, Dr Ignatia Van den Veyver and Dr Elliott Sherr, who both research Aicardi syndrome and have shared their work with patients' families at many family conferences, are also great role models.

What's next for you?

K.P.: I will be completing my master's degree in May of 2025. After graduation I plan to get a job in the biotech field. After gaining industry experience, I plan to pursue my PhD.

S.B.: I am currently a postbaccalaureate researcher investigating the role of chromatin structure in gene regulation in Dr Pedro Rocha's lab at the Eunice Kennedy Shriver National Institute of Child Health and Human development. I hope to pursue an MD-PhD to investigate rare diseases such as Aicardi Syndrome and offer specialized care in a clinical setting.

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

K.P.: I love to travel, explore different cultures and try new foods. This year I have had the privilege of visiting three different countries and I hope to continue traveling after finishing my degree!

S.B.: I will always accept a challenge for a handstand contest! After doing gymnastics for a decade, I still enjoy being upside down.