Sep 18, 2023

Dr. Lianna Kyriakopoulou: Medical Genomics Faculty Spotlight

Medical Genomics
By Teresa Brooke-Lynn Coe

Dr. Lianna Kyriakopoulou is a clinical biochemist and molecular geneticist with an expansive expertise. She is passionate about bringing new technologies into clinical spaces while also empowering those around her to learn and engage with clinical genomics in a meaningful way. A pioneer for personalized medicine, she is currently working to implement RNA sequencing as a comprehensive clinical tool – an unprecedented task that will pave the way for widespread implementation across Canada.

Photo of Dr. Lianna Kyriakopoulou

Lianna is currently the director of Genome Diagnostics at the Hospital for Sick Children (SickKids), an associate professor with the University of Toronto Department of Laboratory Medicine and Pathobiology, and a highly featured guest lecturer throughout the Medical Genomics program (MedGen). She received her PhD from the University of Toronto in genetics and microbiology focusing her work on the cloning and characterization of genes associated with heat shock proteins in micro-organisms. Heat shock proteins are “a very interesting group of molecular chaperones that are involved in the [protein] maturation, refolding and degradation of all other proteins in the cell.” Lianna specifically studied the differential expression of RNA produced from these genes, demonstrating that heat shock proteins are induced by many different stressors and that they help regulate cell growth and survival. Studying RNA expression provides a more context-specific understanding of function as transcribed RNA reflects real-time cellular activity and responses to environmental stimuli. It was through this work that Lianna gained a deep “enthusiasm and an excitement about genetics.”

Completing her PhD during the height of the Human Genome Project, Lianna became enamored with the potential healthcare implications of sequencing the human genome, “realizing there was a whole other world there which was more clinical”. She then completed her first post-doctoral training in clinical biochemistry (Fellow of the Canadian Academy of Clinical Biochemistry), “a clinical discipline [that gives] PhDs the opportunity to work in clinical laboratories.” Subsequently, she went “back to school” to receive additional post-doctoral training in clinical and molecular diagnostics (Fellow of the American College of Medical Genetics). These specialty programs allowed Lianna to develop specific skills and knowledge for clinical work. Nevertheless, she expresses how valuable a strong background in basic research/science can be to understand mechanisms of disease, technology, and tests utilized in clinical laboratories and research.

As a clinical lab director, Lianna is responsible for overseeing the functions and goals of the SickKids Genome Diagnostic Laboratory. The primary objective of the Genome Diagnostic Laboratory is to interpret genetic and genomic test results that inform patient diagnosis. This merely scratches the surface – “we are really in the interface between the clinical service and the development of new tests and technologies”, Lianna explains. Much of the work done by the lab is translational efforts to bring new technologies into clinical practice. Moreover, she outlines the importance of working with clinicians from many different specialties to develop new tests that not only can be used to diagnose patients but can also help with treatment options and monitoring progress. She clarifies that this work differs from basic or translational research, saying “[In diagnostics] we are responsible for providing testing for as many diseases as possible… in contrast to the basic research where most times you're focusing in one particular disease, trying to understand the underlying mechanisms and biological processes.” Overall, the goal is to improve patient care by fostering a laboratory that serves its clinicians and patients.

Lianna aims to create “a clinical lab for functional genomics” as her personal interests involve “bridg[ing] genomic information with functional information”. She often looks for ways in which functional genomics can provide new diagnostic insights. Interested in RNA since her graduate days, Lianna’s latest and largest project has been implementing RNA sequencing (RNA-seq) tests for clinical labs.

RNA-seq(learn more about RNA-seq here) is a genomic technique that sequences RNA copies within a sample, capturing the dynamic gene expression, alternative splicing, and gene fusions. Lianna clarifies, RNA-seq can provide “important insights into the impact of many DNA variants on RNA and help us classify these variants as pathogenic or benign.” However, RNA-seq is not yet fully incorporated into clinical workflows due to technical difficulties and data complexities.

Lianna and her collaborators (Drs. M. Wilson, J. Dowling, K. Yuki, and A. Shlien) have developed a clinical RNA-seq pipeline for rare disease diagnosis: (1) to assess defects in RNA splicing and (2) to assess the increased or decreased expression of a gene. They also developed a pipeline to assess RNA fusions in pediatric cancers to help guide treatment. A gene fusion occurs when “pieces of different genes are fused in-frame and can be translated into a novel protein that may act as a cancer driver”, Lianna explains. Using RNA-seq, Lianna and colleagues were able to detect fusion events in pediatric cancers and show that fusions events in childhood cancers can more abundant that previously believed. She excitingly expanded that this could lead to more targeted treatments as many of the fusions “could potentially be used for therapeutic purposes”. Not only do these results demonstrate the expansive scope of the RNA-seq project, but they also validate the value RNA-seq can have in clinical labs.

Lianna started working on this project three years ago and it was a massive undertaking, as the team needed to design the workflow from scratch. Lianna described having to “go literally into the research space,” needing to identify the most promising chemistry, develop a bioinformatic pipeline, test the protocol with thousands of samples from different cohorts, and determine how the test would fit into the healthcare system itself. She explains that the depth of this project is rare for clinical labs. Usually when bringing new technologies into the lab there is translational pre-clinical research and lots of evidence to paint a pathway towards implementation. For this project however, there was only basic research to build from, requiring them to partner with Dr. Michael Wilson, a researcher at the SickKids and The Centre of Applied Genomics (TCAG).

Lianna has been involved in many projects over the course of her career so far, however she describes this project as one she is the proudest of since her PhD work. This is because “it came at a time in [her] career that [she] had both the opportunity as well as the ability to start it from the very beginning”. It was exciting for Lianna and her team to build this workflow up from the bottom and address the challenges along the way.

They are now in the implementation stage which affords new barriers to address: determining where RNA-seq fits in the clinical workflow and finding funding within the health care system. Lianna explains these are common barriers that occur when bringing new technology into clinical labs, requiring advocacy and collaboration to address them. Lianna asserts that this test will fit beautifully into the clinical workflow, capable of providing independent diagnoses as well as additional information when used together with current diagnostic tools (like whole genome sequencing or gene panels). Thus, it can be utilized for diagnosis clarification as well as disease monitoring and treatment guidance. However, she describes finding funding as one of the biggest and most complex issues for new technology implementation. Regarding RNA-seq specifically, Lianna explains that its price is “practically identical” to DNA sequencing methods currently used in clinical labs as they have the “same technology in terms of the chemistry pipelines, computational time, interpretational time”. As such, Lianna continues to advocate the coverage of RNA-seq tests within the healthcare system so “it becomes available to everyone who needs it in Ontario and across Canada.”

Although her director role keeps her busy, Lianna is also a dedicated educator and mentor. Her broad expertise has allowed her to train students at many different levels, including undergraduates, graduates, fellows, and medical residents. In the MedGen program, Lianna has become a valuable reoccurring guest lecturer, covering topics from epigenetics, pharmacogenetics, RNA sequencing, and more. She has also mentored many students past and present through employing student volunteers and supervising practicums.

Lianna is drawn to teaching as it allows her to “[be] part of someone’s learning” while also being “an opportunity for [her] to learn”, indulging in the reciprocal nature of the learning process. She thoroughly enjoys classroom discussion and student questions, stating they can be “the greatest joys”. Her teaching philosophy revolves around empowerment and fostering a love for the subjects being taught. “I hope that I can empower somebody to learn… to let them grow”, she says explaining the dynamic nature of her teaching. Lianna aims to nurture independent thinkers who are galvanized to further explore topics further. Furthermore, she values the opportunity to teach to also advocate for the topics she loves – clinical biochemistry and genetics – inspiring the next generation of researchers and clinicians.

It is this passion that makes Lianna such a valued addition to the MedGen program. “I thought it was one of the most exciting programs that had been created in recent years”, she exclaimed when discussing her involvement in the program. She further remarked that the program’s ability to transform genetics and genomics education into a practical skill set will help to move clinical genomics in Canada into the future. Expressing her enjoyment for the program and the caliber of its students, she remarks that being a part of the MedGen program “has been an amazing experience…[and] one of the most exciting parts of [her] teaching.”

Dr. Lianna Kyriakopoulou is a celebrated researcher, advocate, and educator and a true icon in the world of clinical genomics. She is a highly accomplished clinical biochemist and molecular geneticist, currently revolutionizing health care by spearheading the implementation of RNA sequencing into clinical labs. Lianna’s inclusion in MedGen adds so much for our students, and we couldn’t be prouder to have her on our team.