Lida is interested in cell differentiation during embryonic development and how this occurs. Through her research, their team may have discovered a congenital disease. Such an amazing experience to have basic research suddenly have direct clinical implications!
Here is a bit more about Lida and how she came to Jennifer Mitchell’s lab!
What is your position in the lab?
I’m a seventh-year PhD candidate in Dr. Jennifer Mitchell’s Lab.
What species do you work with?
C57 and CD1 mice
Where has your research taken you?
My research has brought me to Canada! Intrigued by stem cell research, I joined the Mitchell Lab to pursue my passion abroad and to learn from top researchers in the field. During my graduate program at CSB, I was fortunate to present my work at international conferences such as International Society for Stem Cell Research (ISSCR annual meeting-Melbourne, 2018) and 79th Society for Developmental Biology conference (Virtual, 2020), and national conferences such as Medicine by Design (Toronto, 2018) and 10th Canadian Developmental Biology Meeting (2020 – cancelled due to COVID19). Being able to participate in such events has broaden my horizons as to the potential use of stem cells and model organisms to recapitulate variety of diseases and provide hopes for treatment, as well as interacting with globally renowned researchers. This led to collaborative opportunities with extra-departmental research labs led by Dr. Phyllis Billia (UHN) and Prof. Andrea Jurisicova (LTRI) to accomplish our research goals.
What drew you to pursue a career/education in research?
Interestingly, my undergraduate program had no research component but during a seminar course we were given the option to present a research topic/paper. In preparation, I came across an article that discussed the potential of using stem cells to treat Parkinson’s disease. The flame of curiosity was ignited and since then, I’ve been exploring the molecular processes that define stem cell identity and these cells’ potential to form into different cell types. I believe, as we better understand how cell fates are determined in the context of normal developmental processes (like embryonic development), we can apply that knowledge for diagnosis, treatment, and prevention of detrimental medical conditions.
Have you made any discoveries that you weren’t expecting?
Definitely. When I started my project, we were interested in understanding the role of Myelin Regulatory Factor (Myrf) in embryonic stem cell identity, maintenance, and differentiation. However, after establishing our mouse line, sporadic deaths in adult heterozygous mice (mice that carry a single copy of the gene) exhibited a reoccurring phenotype that may affect adult development. Necropsy examination of a few samples showed that these mice have smaller hearts than normal mouse hearts. And so, we pursued an analysis of this phenotype with our collaborators for cardiac assessments, which confirmed Myrf heterozygous mice have decreased heart function. Considering that at the same time reports of cardiac complications in human cases were being published was indicative of how our work can be used to understand such conditions.
What are some challenges you have come across and/or overcome in your research?
Having worked with mice and rat subjects prior to my PhD gave me confidence to believe I can manage any unexpected results in future mouse projects. However, establishing our animal colony and modes of assessment for embryonic lethality was not an easy task. Based on our preliminary data using mouse embryonic stem cells, we anticipated a completely different time and cause of lethality which meant our initial hypothesis required modification and new lines of investigation. Such challenges are very common and can happen to any investigator at any time during their research, however it is also an opportunity to test new theories. Pursuing our new trajectories has opened new possibilities that were not only interesting at first but also more accurately in line with human cases pointing towards a new congenital disease never reported before. Overall, this proved a very educational experience.
Tell us about your research and any ongoing studies or projects.
In most multicellular organisms, life begins with a single cell (zygote) and that single cell divides and differentiates to a myriad of different cell types which form a full functioning organism. The genomic/DNA content of all cells are the same but the way which the genetic code is read and interpreted is different according to cell type. In my research, I’ve explored the role of a Myrf in mouse embryonic development. As the name implies, this transcription factor is crucial for central nervous system myelination. However, Myrf is expressed during embryonic development and myelination occurs after birth which indicates a broader regulatory role for the gene than previously thought. Using a mouse model, I’ve confirmed that loss of Myrf (Myrf-Null) can lead to embryonic death at embryonic day 11 (Figure). Furthermore, the absence of Myrf can cause developmental delay, suggesting a fundamental role for Myrf at the molecular level. We are currently exploring these possibilities using both in vitro and in vivo approaches to elucidate the molecular mechanism causing embryonic lethality.