When Kathy Fange Liu graduated with her PhD in chemistry from Georgia State University in 2013, the study of RNA was an area of untapped potential.
“When I graduated, RNA wasn’t as big a topic as it is today — I didn’t know much about it,” Liu said. “My advisor encouraged me to explore RNA because there was a need and an opportunity to make a real impact. Additionally, the study of RNA was a natural fit for my enzymology background, so I ended up going to a few conferences to learn more. This was the foundation for my current research. Essentially, life pushed me in the right direction.”
Liu, now an assistant professor of Biochemistry and Biophysics and principal investigator of the Kathy Liu Lab in the Perelman School of Medicine at the University of Pennsylvania, specifically studies enzymes that modify RNA in the body’s cells that can impact human disease. RNA is essentially the bridge between DNA and proteins that helps proteins do their everyday work.
Following her postdoctoral training at the University of Chicago, Liu landed at Penn in 2017. “I actually interviewed at 16 different places and, in the end, I felt it was very straightforward for me — Penn is outstanding, especially because of the collaborative research environment,” Liu said.
In the following Q&A, Liu describes her current research and her motivation to continue to push boundaries.
What research are you currently undertaking?
My laboratory studies the function of RNA modifications and how those functions contribute to human physiology and disease. RNA exists in a variety of forms, each with a particular role and purpose. All major types of RNA carry chemical modifications, which impact nearly all steps in RNA processing, including RNA stability and translation properties.
We also study sex-specific RNA regulation in cancer. The frequency and severity of many types of human cancers differ between males and females. One of the significant keys to sex-biased differences lies in the sex chromosomes. Females generally have two X chromosomes while males have one X chromosome and one Y chromosome. The Y chromosome is actually very small — it only contains one tenth of the genes on the X chromosome. The function of Y chromosome in cancers in non-reproductive tissues is unknown. We are specifically focused on studying the function of Y chromosome proteins with the goal of understanding their roles in sex differences in human disease, such as cancer and infectious disease.
What is unique about your RNA-focused research?
Previous research has shown that a variety of enzyme-mediated modifications — or genetically coded enzymes that install and remove chemical modifications to regulate gene expression at the RNA level — are found within RNAs, which markedly influence the fate of RNAs in cells, such as RNA stability and properties in protein translation.
Despite modifications occurring in RNA species simultaneously, the research field historically focuses on the function of one modification in one RNA species. Since the inception of my laboratory in 2018, I asked a new question: whether and how modifications across RNA species work together to influence gene expression in disease.
As the COVID-19 vaccine research exemplifies, modifications in the mRNA vaccine can dramatically increase the effectiveness of the vaccine at inducing the body’s cells to make spike proteins that prime the immune system to fight SARS-CoV-2. My group is studying the coordination of modifications in different RNA species to influence translation of RNA into proteins which may further modify the effectiveness of mRNA vaccines. Additionally, I have a long-lasting interest in understanding sex differences in human disease. So, when I opened my lab, I immediately started to explore the role of RNA enzymes that are encoded in genes on the sex chromosomes in human diseases that affect the sexes differently.
What are the biggest challenges you face as a scientist? Where do you see the greatest opportunities?
For me, my biggest challenges and opportunities often overlap. I’m constantly asking myself, what is the real impact for my research? What is the boundary and how can I push it? What will make the biggest difference? It’s very exciting but it is also challenging because you always have to identify the most urgent need and continuously push your work to the research frontier. I’m very proud of all that has been accomplished — the lab is doing really well, I publish, I get grants — but I’m also always thinking about what’s next.