Life as a Ph.D. Student with a Passion for Myeloid Leukemia
Interviewed by Leon Lin, RND at STEMCELL Technologies
I met Courteney when we were both graduate students in neighbouring labs at the BC Cancer Research Center. I was a new graduate student who needed help with the automated cell counter and Courteney was nice enough to come introduce herself and help me out. Originally, our labs were located 2 floors apart, but when my lab moved to her floor, we found out we both worked on similar things (myeloid leukemia) and used similar assays. Here we began to talk more. I then moved to the same office as Courteney, and we found out we both played ultimate frisbee - the talking increased! Courteney is completing her PhD studies in Experimental Medicine at the University of British Columbia. During her PhD, Courteney has focused on using AML models involving overexpression of transcription factors and cofactors to uncover the relationship between oncoprotein structure and leukemic properties and identifying key genes and pathways underlying leukemogenesis. Outside of the lab, Courteney is passionate about scientific outreach, education, and advocacy, volunteering with numerous organizations such as StemCellTalks Vancouver and SCWIST.
Leon Lin: Okay, expert - when did you first know you wanted to be a scientist?
Courteney Lai: I had a really great science teacher in grade 10. Throughout the year we were encouraged to bring in news articles featuring scientific discoveries. Every week he would go through the submitted articles and pick out a few to talk about. This emphasised the connection between what we were learning in class and work done in a lab and how it affects people in the world.
LL: Other than lab work, what is something you do as a hobby - something that you enjoy doing outside of the lab?
CL: I am really passionate about outreach and engagement in science. Science influences our lives every day, and, considering so much of scientific funding and research is funded by taxpayers, it is so important to do our part to engage the public. I’ve done a lot of things during my academic career in terms of organizing and being involved in these kinds of initiatives, including advocating for trainees in my grad student organization, mentoring high school and elementary school students and speaking at conference aimed at getting women involved in science.
Outside of science, I’ve been playing ultimate frisbee for about 8 years, in addition to baking and running. These things keep me grounded in the world outside of research, regardless of what happens inside the lab.
LL: Speaking of frustrations in the lab, how do you deal with setbacks during experiments?
CL: Different things work for different people. For me, I think part of it is putting things into perspective. Sometimes things don’t work and often our first instincts are to assume it is something we did wrong with a protocol or procedure. First I look back to ensure it wasn’t a mistake on my end or if it was, how to avoid it in the future. But just as frequently, it seems that it’s not a technical mistake - it’s just we are asking the wrong question or trying to answer our question with the wrong experiment. Basically, don’t dwell on the fact that something failed but move into how to make it work or figure out why it’s not.
LL: Let’s talk more about your research, perhaps you can give us some background and the current goals of your work.
CL: So the focus of my PhD is to identify and gain a better understanding of the key regulators of leukemic stem cell function. A lot of my work has been using models of Acute Myeloid Leukemia (AML) - basically using models with overexpression of transcription factors to uncover factors that influence properties of leukemogenesis such as its transformation, initiation and progression.
Part of my studies involve elucidating the relationship between the structure of an oncoprotein, and it’s leukemic properties. Could we ascribe specific leukemic properties to specific regions of the protein and what does this tell us about how single hit oncogenes are capable of having an effect on cells. Subsequent to that I also focused on using this information in a broader perspective to investigate the heterogeneity of leukemic cells and determine what is happening on the molecular level that underpins these differences. This can help us understand the cellular makeup of leukemias, and hone in on potential genes or pathways that can be targeted therapeutically.
LL: What is your favourite tool in the lab to use in your work?
CL: Flow cytometers are pretty amazing due to the fact that there is so much information that you can get from them. They are so powerful these days though they can behave erratically and need a lot of attention, but luckily we have an amazing flow core to keep the machines running and supporting different assays that we come up with. Flow is especially important when looking at leukemic stem cells using single cell sorting, which is such a critical tool to be able to do all of these assays.
LL: Perhaps you can share some of your expertise with us, what do you think is the most interesting finding to be published recently?
CL: I can’t pick out one in particular. In general I’m very impressed by the level and complexity of big papers that are coming out, how quickly people adopt new tools and technologies as they are published. For example CRISPR is very new but quickly being adopted as a game changer in how precisely and efficiently you can manipulate genes. The other exciting thing is the increased appreciation for the inter connectedness between molecular and cellular regulatory systems including epigenetics, transcription factors and the microenvironment. There is increased appreciation for collecting and examining information as a whole, as well as the ability to go deep into deep seq and single cells to track these kinetics and how everything affects everything else.
LL: Are they trying to use all these new technologies to better understand AML?
CL: One intriguing area is better understanding the events that occur from initial transformation events, through the pre-leukemic state and into leukemic development, progression and relapse. Using these technologies, we have improved abilities to specifically target and manipulate different parameters in an efficient and thorough manner, providing vastly improved specificity for creating the conditions we are studying. Through better understanding of the events that occur and their consequences at each of these stages, we are both gaining a deeper appreciation for the complexity of the leukemic process, while improving the models we use to study this disease.
LL: Do you think creating targeted therapies is the next step?
CL: Yes, and it’s also where to draw the line between the push of personalized medicine - looking at each patient and the best way to treat them, while balancing this with the amount of time and resources that takes. Basically finding the happy medium between developing the ideal treatment plan for each patient and how we have treated AMLs in the past with major doses of chemotherapeutics that may not work for everyone. Likely, that happy medium will lie in the identification of key markers that will help classify patients for their best treatment plans.
LL: What piece of nonexistent or “sci-fi” technology could’ve helped you finish your PhD in half the time?
CL: One of the things that would be really cool is the ability to know before hand if you have a leukemia or hematopoietic stem cell. The gold standard readouts are retrospective and in vivo, basically you do an assay with a hematopoietic stem cell and can say ‘Oh, I had an HSC’ but at that point, it’s gone. It would be great to be able to sort cells and look at a tube and know the number of HSCs you have. That, or automated mouse processing; your mouse gets sick and all the relevant tissues are analyzed, blood counts are done, flow cytometry is done and you get a print out at the end within 30 min. That might be too much to ask…
LL: If you could have one useless superpower what would it be?
CL: Well, the ability to have a giant pause button on time, but it doesn’t affect me. I could pause everyone, and use all the machines - or just take a nap!
LL: Yeah that would be pretty useful actually..so what is your plan now? Are you looking for postdoctoral fellow positions?
CL: I have been working on my thesis, which has been pretty all-consuming - looking at everything you have done throughout your degree and bringing it together into a cohesive narrative. Now I’m shifting gears to think about what my next steps will be after my defense, likely off somewhere new for a postdoc position. Then taking a brief “vacation” to work on thesis revisions once those get back...there are still some things to finish in the lab.
LL: Well that was wonderful. Thank you Courteney it has been great speaking with you!
This interview has been condensed and edited.
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