Our First Original Research Article
Our lab has reached one of many eagerly anticipated milestones: the publication of the first original research. The story of this manuscript is a narrative of my research lab and I am happy to document that story here as a behind-the-scenes of a scientific story.
I was a postdoc for a long (long!) time, and that was mainly spurred by the complexity of my main project. I never held any aspirations for a faculty position but remained at my post because of a sense of duty to complete my project. After many years of data collection, peer review, rejection, and resubmissions, the project that helped to launch my career was published in 2019.
However, during that time I was not solely working on this project, as my position was covered by a P01 grant from the National Institute of Aging. I started collecting data investigating the aging thymus, and this project allowed me to interact with some distinguished scientists in the field of T cell and thymus aging. This experience got me interested in immune aging and also demonstrated to me that the reasons why the immune system changes as we age are still very mysterious.
Towards the end of my postdoc, my mentor shocked me by suggesting that I should apply for faculty positions. I had heard all the negative stats about how difficult it is to transition from postdoc to faculty, with estimates of <10% of postdocs becoming professors. Surely, someone who haphazardly navigated the Ph.D. path, without a prestigious pedigree or transitional funding, would not be taken seriously for a job that has potentially hundreds of applicants. But, I am a dreamer, and so I took up the challenge and began to apply in earnest for faculty jobs.
Part of the faculty job application is to write up a description of Research Interests. The rest of the package covers your achievements, but this is where you need to dazzle a search committee with what you intend to do with their job and money. I asked my mentor for one day per week to spend outside of the laboratory in order to work on my faculty job search. I spent this time in the local public library reading articles and searching for inspiration. I was particularly interested by several articles (1, 2, 3) that suggested global changes to the lymph nodes were correlated to changes in T cell immune function. What was missing from these interesting articles was exactly WHY changes in tissue structure drove immune decline. I wrote this story up in my Research Interests to complete my research package.
I started my lab on March 2, 2020; one week later, the pandemic altered everything. I spent the first couple months trying to figure out how to get my lab started, especially in an environment where research activities were interrupted. I needed to feel like I was making progress, so I began asking around for materials. Labs studying multiple myeloma and allergy kindly let me harvest the unwanted lymph nodes from their specimens. I paid histology services to prepare slides for me and then worked alone in my lab, learning how to stain the slides (a new technique for me). Also, figuring out what microscopes were available on campus for me to use. Slowly, these initial experiments supported what the earlier investigators had published: lymph nodes start to look weird as an organism ages.
Over the course of the following year, I supervised the efforts of my technician, postdoc, and graduate student, as well as 4 undergraduate interns. I started to carve a story out about these aging lymph nodes. Based on my earlier reading in the public library, I homed in on a structurally supportive cell of the lymph nodes (the fibroblastic reticular cell) and started to build a story about how they change as we age. Their changes feed back to the T cells that need them. I began to postulate why these changes are occurring. I reached out to experts (Anne Fletcher and Alexei Tumanov) in the field to be sure they thought I was making sense.
Young T cells (green) are captured by 2-photon microscopy actively migrating within the young lymph node (black space with blue border). Color-encoded time tracks of T-cell migration. Copyright: Kwok, et al., Frontiers in Aging, 2022
2-photon microscopy reveals that even young T cells (green) are slowed down by fibrotic deposition (blue) in the aged lymph nodes. Color-encoded time tracks of T-cell migration. Copyright: Kwok, et al., Frontiers in Aging, 2022
The photographs above are stills from the videos that were published. Unfortunately, I don’t have a great method to embed the videos here on the blog, but I encourage you to view the videos on the supplementary material of the article.
My story was still descriptive though, as I could only hint at this mechanism of change. However, as a new investigator, I knew I needed to start putting myself on the map. Even in this niche area of lymph node cells, there are prominent investigators with big labs. Upon invitation to submit an article to the new journal Frontiers in Aging, I committed myself to get the paper out for peer review.
It has been so rewarding and also so astonishing that a small knowledge gap that I identified in the field could be developed into a new hypothesis regarding the way biology works. It is still too early to say what impact my work will have on the field, but it feels humbling that my work is out there. I feel the internal and external pressure to succeed—there is a lot riding on whether I could find something substantial in my first year. I know that it is ok for a hypothesis to be wrong, but I am lucky that my intuition along the way guided me to this first original publication. The data surprised me, as it did not turn out exactly as I expected and there are still many questions. I have recently finished writing a grant proposal to study the aging lymph nodes and their impact on immune function. I have slowly learned that this is the way of science, and it is quite an amazing journey.