ABSTRACT
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. Ana Diaz Espinosa is first author on ‘Dopamine D1 receptor stimulates cathepsin K-dependent degradation and resorption of collagen I in lung fibroblasts’, published in JCS. Ana conducted the research described in this article while a Post-baccalaureate Research Education Program (PREP) student in Daniel Tschumperlin's lab at the Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN. She is now a PhD student at the Mayo Clinic Graduate School for Biomedical Sciences, investigating how to restore cellular and tissue function by integrating fundamental principles of biology and biomaterials.
Ana Diaz Espinosa
How would you explain the main findings of your paper in lay terms?
A healthy lung possesses a group of cells called fibroblasts, whose primary job is to maintain the structure of the lung that supports our ability to breathe. Fibroblasts are activated at times when this structure has been damaged to add and remove proteins from the tissue and repair the structure. Idiopathic pulmonary fibrosis (IPF) is a disease characterized by the continuous activation of fibroblasts, which then add more proteins than needed to the structure, resulting in the formation of scar tissue in the lung. This excess of proteins increases the stiffness of the tissue and prevents the lung from expanding, reducing our ability to breathe. Our study presents an approach to stop fibroblast activation and shift their behavior, so that instead of adding proteins, they remove the excess and restore the function of the lung. At a cellular level, this change in behavior is driven by a reduction of the pH in the lysosomes of the fibroblasts, which activates cathepsin K, an enzyme that removes the excess protein from the tissue.
Were there any specific challenges associated with this project? If so, how did you overcome them?
One of the challenges we overcame was to demonstrate that stimulation of the dopamine receptor D1 specifically altered the extracellular compartment, rather than uniquely stimulating intracellular degradation pathways. To prove this, we enhanced traditional techniques by incorporating experimental designs and novel tools that allowed us to differentiate intracellular and extracellular degradation, rather than just exposing the absence or presence of protein as a result of stimulation. Among these approaches, we highlight the development of de-cellularized cell-derived matrices analyzed by AFM microindentation, and the use of DQ collagen and collagen-hybridizing peptides as markers of collagen I degradation in vitro and in vivo, respectively.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
Observing that lung fibroblasts have the ability to degrade collagen I in vitro and in vivo, because it opens a window of opportunity for new research directions.
Why did you choose Journal of Cell Science for your paper?
Journal of Cell Science is a synonym for scientific excellence and novel perspectives, with rigorous and ethical review of the manuscripts submitted. Encouraged by these values, our group was eager to publish and disseminate our findings in this great journal.
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
I am grateful for the guidance and support I have received from Dr Daniel Tschumperlin, Dr Andrew Haak and Dr Luis Lujan. Their mentorship was special, as they were considerate of my overall wellbeing as well as encouraging scientific rigor, pushing me to think outside of the box and to purse excellence. I was in a nurturing environment where I felt comfortable discussing experimental drawbacks, data misinterpretation, oral and writing skills and even topics related to student health and wellbeing. By sharing their experiences, they became relatable, and made me realize that obstacles create an opportunity for growth.
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?
During my first research experience, I made the connection between what I had been learning inside a classroom and a real life application. I replaced the image in my mind of the beautiful drawings inside a textbook with vivid representations of what a cellular environment looks like. And this was not the finish line; as I kept growing as a scientist, my ability to develop hypotheses and explore questions that had the potential to impact the life of a patient in the future settled this idea in my head of becoming a scientist. This first experience made me reflect on the privileged position that we hold, being at the frontline of research where we can aim towards a healthier and sustainable future by collaborating and discussing new findings.
What's next for you?
I have recently started to pursue a PhD in Biomedical Engineering and Physiology at the Mayo Clinic Graduate School for Biomedical Sciences. With this experience I am excited to keep growing as a scientist, to continue shaping my interests and to use this knowledge to contribute to the advancement of healthcare.
Tell us something interesting about yourself that wouldn't be on your CV
I am an avid explorer and traveler, and an amateur photographer, born and raised in Colombia. From a young age, I enjoyed dancing and practicing sports – competing in local leagues for basketball. Today I celebrate diversity, strive for success and aim to lead by example and inspire others to be their best version of themselves.
Do you have a message to future scientists?
My advice would be to embrace who you are and don't be afraid to think differently. Your culture and heritage make you unique and give you the opportunity to bring creative ideas and different perspectives into your research field. In addition, I would encourage scientists at all levels of education to enjoy the journey! Mistakes are an opportunity for learning, improving and becoming a better scientist. Trust that you have what it takes to be successful, and surround yourself with people that are moving in the same direction as you are.
Ana Diaz Espinosa’s contact details: Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.
E-mail: [email protected]