First person – Baishakhi Ghosh and Kristine Nishida

Baishakhi Ghosh (left) and Kristine Nishida (right)

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

B.G. & K.N.: Chronic obstructive pulmonary disease (COPD) is a devastating lung disease that leads to difficulty in breathing, afflicting 15% of the population of the USA. Chronic exposure to cigarette smoke is the primary cause of COPD, with injury persisting even after the removal of noxious insults. The epithelium lining the lung is crucial as it forms the first contact with inhaled agents and establishes a physical barrier to protect the body from inhaled noxious agents. The lung epithelium is vulnerable and undergoes structural and functional changes (also called ‘plasticity’) upon exposure to irritation or injury. We have characterized the injury response of the lung epithelium by quantitatively measuring the monolayer permeability, monolayer height, ciliary function and cell motion. We found that in response to this chronic injury, the epithelium took on some characteristics indicative of the transformation of cell type, but retained some other features suggestive of collective motion, similar to what is seen with the disease. These changes in both COPD and cigarette smoke-injured lung epithelium are mediated by lower levels of cofilin-1, which allows for an increase in polymerized actin. Strategies that reduce the fraction of polymerized actin in the epithelium could have therapeutic benefits in COPD.

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

B.G. & K.N.: As cell biologists, we made many exciting observations. But making quantitative measurements to explicate those observations was a challenge. We were fortunate to have collaborations with Dr Joseph Katz (Professor, Johns Hopkins Whiting School) and Dr Lakshmana Chandrala (a postdoc), who helped us with translating the microscopic images into quantitative measurements (such as cell shape, cell velocity, spatial distributions and energy of cell motions).

Another challenge that we experienced while addressing reviewer comments and suggestions is the complete shutdown of resources to access the microscope core facility and laboratory space available due to the COVID-19 pandemic. But gradually, when the resources and lab opened with restrictions, we were successfully able to perform the experiments and address the reviewer's comments.

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

B.G. & K.N.: We had two eureka moments while performing the present research.

Early on in our research, we decided to image the cells over time based on an epithelial unjamming idea by Dr Jeffrey J. Fredberg. A big eureka moment was when we saw that the cells were indeed moving!

Another exciting moment was when we were screening for cytoskeletal proteins that were possibly associated with COPD and found cofilin-1 as a very interesting protein with a biphasic relationship that might contribute to understanding the injury in COPD.

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

B.G. & K.N.: Journal of Cell Science (JCS) is a renowned journal that reaches a broad scientific community involving research-active academics and leaders with an interest in dissecting the complexity of diseases with mechanistic research findings. We admire JCS for its support to early-career researchers and ensuring the utmost quality and rigor in reported findings.

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

B.G.: A productive and supportive mentorship establishes the fundamentals for postdocs and stimulates their careers. Dr Venkataramana Sidhaye provided distinctive mentorship that enriched my research knowledge in the field of respiratory diseases, skills and productivity. Dr Sidhaye also provided me with a platform for mentoring the students, which has improved my teaching and communication skills.

K.N.: My first research experience outside of undergrad was in the Sidhaye lab. Dr Sidhaye's mentorship was unique in that I was given a lot of responsibilities and opportunities despite my minimal experience. As a result, I grew immensely both as a researcher and personally.

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?

B.G.: Dr Ronald J. Mascarenhas (Associate Professor, Department of Chemistry, St. Joseph's College for Arts & Science, Bangalore, India) was the first person to introduce me to research. Dr Mascarenhas gave us a class assignment in my undergrad on finding different sources of references/bibliography in research. As I was working on this assignment, I was influenced by how research is built upon what other people have previously done. This has formed the foundation of my research career. Gradually, during my MSc and PhD, I got exposure to international-level mechanistic research experience and learned about collaborations, and gained interdisciplinary research experience by working with mentors like Dr Lindsay J. Marshall (former Senior Lecturer in Immunology, School of Life and Health Science, Aston University, Birmingham, UK), Dr Sundeep Salvi (former Director, Chest Research Foundation, Pune, India), Dr Peter Barnes (Senior Research Investigator, Imperial College of London, National Heart and Lung Institute, London, UK) and Dr Louise Donnelly (Professor, Imperial College of London, National Heart and Lung Institute, London, UK).

K.N.: My first introduction to research was as an undergrad. I greatly appreciate my mentors as they introduced me to science and have instilled a sense of excitement for research. Collaborating with engineers on several different projects was unexpected, but those experiences are what eventually led me to the field of process development for cell and gene therapies.

Who are your role models in science? Why?

B.G.: At each stage of my research experience, my family, friends, colleagues, current and previous principal investigators have been the role models for me in many aspects of my overall career. The interactions and experiences with them have taught me the importance of curiosity and perseverance in science and life, which has helped me to grow as a person.

K.N.: I don't have any specific role models in science. However, I feel that I have learned many different things from each and every person I have worked with. Those people and experiences have taught me what I would like to emulate in my own scientific career.

What's next for you?

B.G.: Over the years, I have enjoyed contributing towards knowledge generation in cellular and molecular mechanisms in lung diseases. My plan is to continue my academic pursuit as a Research Associate and contribute scientifically towards therapies to improve the quality of life of patients with lung disease. I hope to obtain independent funding and become an academic investigator with a combination of teaching and research.

K.N.: I am currently working as a research associate in process development at a biotech company. I plan to stay in the field focusing on R&D/process development.

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

B.G.: I enjoy going on hikes with an elevation gain of at least 450 feet and love capturing the precious sights that can be re-lived in their vibrant glory through my DSLR camera (hobbies I developed after moving to the USA!). One of my favorite hikes is Myrtle Point in the Great Smoky Mountains and Mount LeConte via Alum Cave Trail, Tennessee (length of 13 miles and an elevation gain of 3097 feet) with a beautiful breath-taking view at the top, which I did with the wonderful company of my husband.

K.N.: Interestingly, the personal relationships I have made between lab members have continued beyond the lab. We still keep in contact and meet up from time to time. It is exciting to think that all of the people I have worked with are all over the world and doing great things!