Chun-Kan Chen, PhD

The human genome encodes a subset of non-coding RNAs that are covalently closed forming circular RNAs (circRNAs). As an Assistant Professor, Dr. Chun-Kan Chen is deeply fascinated by the unique structure of these non-canonical RNAs and has recently provided evidence indicating that hundreds of circRNAs in human cells code for proteins. His data adds to results from many labs that support a paradigm shift regarding the function(s) of circRNAs within cells and asking new questions about their possible role(s) in diseases. He has just established his own lab group at the Washington University School of Medicine in St. Louis, USA. His team uses multi-omic and high-throughput screening approaches to systematically interrogate circRNA in cells and to develop novel circRNA technologies for translational applications.

Dr. Chen earned his Bachelor’s of Science from the National Taiwan University in Taipei. He then completed his Master’s studies in Biochemistry and Molecular Biology at the University of Southern California and obtained his PhD at the California Institute of Technology. Throughout his career as an RNA biologist, he has always focused on non-coding RNAs (ncRNAs). Questions like “What makes these ncRNAs special?” or “How do cells utilize ncRNAs to regulate cellular functions?” have always stoked his curiosity. First, as part of his PhD work, he immersed himself in the study of Xist, the long non-coding RNA (lncRNA) required to initiate X chromosome inactivation in females. Under the supervision of Dr. Mitch Guttman, he identified Xist-interacting proteins and showed that Xist serves as a scaffold for multiple proteins that mediate transcriptional silencing. Later, during his postdoctoral work with Dr. Howard Y. Chang at Stanford University School of Medicine, Dr. Chen became interested in circRNAs, which had been considered “noncoding” transcripts since their discovery. Dr. Chen committed to solve the technical challenge that the closed-loop structure of circRNAs posed for the systematic identification of coding circRNAs. “Traditional methods used to study cap-dependent mRNA translation are often not applicable to study translation from circRNAs,” Dr. Chen explains. “To overcome this gap, I developed a high-throughput reporter screening assay that can systematically monitor and quantify circRNA translation. Utilizing this new technology, I was able to show that hundreds of circRNAs in human cells serve as translation templates for protein synthesis, and that their encoded proteins can be detected using mass spectrometry.”  

“When selecting your thesis lab, it's crucial to consider not just the research projects but, more importantly, to find a mentor whose mentorship style and expectations resonate with yours. This choice will have a profound impact on your future career.”

Dr. Chen believes that his work on translation of circRNAs, together with studies from other groups, has elucidated the “uncharted realm of the circRNA-encoded proteome” that had been overlooked previously. He established his new lab 8 months ago with the aim of “revealing the regulatory and functional roles of these circRNA-encoded proteins in cellular processes and diseases.” The guiding hypothesis for his lab is that the regulatory mechanisms that control protein synthesis from circRNAs are distinct from the canonical pathways of mRNA protein synthesis.

To define his research interests and shape his career trajectory, Dr. Chen counted on his mentor’s help during his graduate studies. Based on his experience, he argues that “finding a mentor whose mentorship style, personality, and lab environment align with your preferences is even more crucial than the choice of the research project”. So, he strongly advices to graduate students: “When selecting your thesis lab, it's crucial to consider not just the research projects but, more importantly, to find a mentor whose mentorship style and expectations resonate with yours. This choice will have a profound impact on your future career”.

Dr. Chen acknowledges that the most significant challenge in his career was securing a faculty position because of the unpredictability and protracted nature of the process. Here again, the support from the scientific community was crucial to overcome the stress of the process. “Thankfully, I was surrounded by senior alumni colleagues who had navigated this path successfully before me. Their invaluable advice and shared experiences were helpful in guiding me through this intricate process. I am deeply grateful for their full support. Even now, after establishing our respective labs, we continue to stay connected and catch up from time to time”, he comments.

Now, as a new PI, Dr. Chen faces new challenges mainly related to "non-research" responsibilities that come with setting up a lab. “No one truly prepares you for running a lab independently – from establishing an ordering system and delegating lab duties to coordinating meetings with trainees.” In this case, his colleagues and the department office assisted him during the transition ensuring a smooth start for his lab. Demonstrating that a solid and prolific community can only be built from cooperation and collaboration, he affirms: “I am inspired by the generosity of my colleagues, I am now eager to extend the same support to incoming faculty to assist them in establishing their labs”.

At this year’s Annual meeting of the RNA Society in Singapore, Dr. Chen had the chance to meet great scientists and attended fantastic scientific sessions with high impact talks and excellent posters. He also said that he will always remember how special Singapore was as the host of the conference. He greatly appreciated the opportunity to discovering Singapore’s attractions and activities. “Singapore was just so beautiful, and I had opportunities to experience and savor the country’s culture and delicious food. One of the highlights of my trip was the night market. The variety and taste of the food there left a lasting impression on me. It was truly a unique and memorable experience.”

Dr. Chen’s favorite RNA Journal article is “Circular RNAs are abundant, conserved, and associated with ALU repeats (Jeck et al., 2013)”. This groundbreaking paper was one of the pioneer circRNA studies shedding light on the biogenesis of circRNAs, marking a key milestone in RNA research. It not only revealed the existence of circRNAs but also facilitated the exploration of their regulatory and functional roles. Dr. Chen remembers the impact of this work on his research: “This research was among the first that I encountered in the field of circRNA, inspiring my work on this unique and previously overlooked class of RNAs. The insights provided by this research significantly broadened the horizons of my own work, driving me to study more potential functions of circRNAs. It opened up new pathways in my research, leading me to explore this distinct class of non-canonical RNAs and reveal its roles in cellular processes and disease pathogenesis."

If you are interested in exploring the mystery of circRNAs and their implications, you can contact the Dr. Chen Lab through their website, Twitter account @CKChenLabWUSMCBP or by email at [email protected]. His lab is hiring senior level scientists – staff scientists and postdocs! He will be also happy to simply discuss his favourite RNAs: “circRNAs, of course! Maybe with some lncRNAs as well!