Felix Leung, Clinical Biochemist (in Training)
Felix Leung will graduate this November with a doctorate from the Department of Laboratory Medicine and Pathobiology. He is now a fellow in the department's postdoctoral clinical chemistry program, a two-year diploma that prepares students to work as clinical biochemists.
Leung spoke with Faculty of Medicine writer Jim Oldfield about his role as a clinical chemist trainee, his doctoral research on ovarian cancer with Professors Vathany Kulasingam and Eleftherios Diamandis, and what his future may hold.
As a clinical chemistry fellow, what are you doing now?
I'm rotating through U of T's affiliated hospitals, learning to manage the scientific aspects of their core laboratories and ensuring adherence to external quality assessment bodies. As clinical biochemists, we oversee the measurement of analytes in patient samples (mainly blood and urine), which ultimately help physicians diagnose diseases and make treatment decisions. A major responsibility is to act as a liaison between the lab and doctors, as we often provide advice on the suitability of a particular test and find out whether a test is available in-house or needs to be sent out. Not every test is available in every lab, so there is a lot of cross-talk between biochemistry labs around the city. Sometimes we suggest new tests that a doctor might not know about, such as up-and-coming mass spectrometry-based tests, or we may suggest an alternative test instead of the one a doctor ordered. There's also a lot of interpreting results. If a test comes back outside the range a doctor was expecting, what might be going on? Should the lab re-define the "normal" range, or was the result maybe related to how the test was run? There are a lot of questions to answer and results to mediate.
What happens at the end of your training?
At the end of the two years we do a written and oral exam to become licensed by the Canadian Academy of Clinical Biochemistry (or the ABCC in the U.S.). We can work at an academic hospital, a community hospital, or in a private lab like Dynacare or LifeLabs. I like aspects of all three settings, and I can imagine wanting the experience of one or the other at different points in time. But based on my doctoral training, an academic hospital seems most appealing right now — I really like the idea of a balance between clinical duties, research and teaching.
Are you still doing research?
Technically, 24 hours in a day is not enough right now, but I'm still wrapping up projects with Drs. Kulasingam and Diamandis. The work from the first half of my PhD is done, which concerned validation of new biomarkers for ovarian cancer. Our goal was to develop a blood-based test that could identify people with or at risk of developing the disease earlier than current tests. We validated one marker, a protein called folate receptor 1, but we found it only performs as well as what we have in the clinic now. We did at least show there's no point pouring money into further research on it, which highlights the importance of validation studies.
For the second half of my thesis I focused on rarer types of ovarian cancer. Most patients have what's called the "serous" type, and current markers do well for it. We went after markers for three subtypes, called mucinous, clear cell and endometrioid. We collected a cohort of tissues arising from these subtypes and performed deep proteomic analysis. We're looking for potential markers but also biological pathways that might tell us how how these cancers develop, because right now we lack an understanding of where they come from. They're kind of a black box, although it seems likely that they start outside the ovaries and are only detectable by the time they’ve metastasized to the ovaries. We're analyzing that data now. We have some intriguing evidence that may link some of these subtypes to gastrointestinal and endometrial origins, which I think would be the first proteomic-level data on that potential connection. (Links have been suggested in genomic and other types of studies.) Anyway, a better understanding of the etiology could have a real impact on diagnosis and treatment of these rare ovarian cancers.
Do you want to pursue that research?
I would certainly like to pursue it and I expect to contribute to a manuscript when we write up the results, hopefully this year. But I'm also interested in learning more about the use of statistics in clinical research. That's an underappreciated area that is very applicable to clinical chemistry, where we do a lot of statistical analyses to establish normal ranges for analytes and for quality control. Analytes can have huge variations in healthy individuals, and this makes it difficult to establish a "normal range" that can be applied to all patients. Identifying a sample as too low or too high could have huge consequences for the patient, so we need to be confident in how we define normal ranges. Similarly for quality control, it's often difficult to determine when a test has "drifted" away from how it normally performs. Drift will inevitably occur and we often recalibrate tests after a degree of it, but there are still disagreements on how to define the threshold for drift. I would need more training for research on these issues, likely through a program in biostatistics, but it's a really interesting area of study.
Do you find time for activities outside the lab?
Looking back on my PhD, I was very lucky to have two supervisors who allowed me to do a lot of things outside my studies. I received my diploma from The Royal Conservatory of Music and had many opportunities to participate in orchestras and bands. I was a Residence Advisor at Chestnut Residence for three years, which taught me a lot about interpersonal skills, managing time and conflict resolution — soft skills l continue to use every day. I also played a lot of volleyball at U of T and had the chance to coordinate the UTGSU volleyball league (and met many great people along the way). Overall I had a very holistic experience at U of T, and at times my hobbies helped me regroup mentally and get over hurdles in my research. Often it seems impossible to have a life outside the lab, but there is always time. You just have to make it.