Fighting to outsmart cancer: A Q&A with graduate student Yanqing Liu

Cancers are notorious for finding ways to resist treatment.

Van Andel Institute’s Yanqing Liu, a Ph.D. student in the lab of Scott Rothbart, Ph.D., works to outsmart them by exploring the molecular tricks cancer cells use to survive. Her research focuses on an epigenetic process called DNA methylation, which determines when the instructions in our genes are turned “on” or “off” without changing the DNA sequence itself. When this process goes wrong, it can allow cancer cells to survive and spread. Epigenetic errors are promising targets for cancer treatment because they are, in theory, reversible.

Thanks to a Predoctoral to Postdoctoral Fellow Transition Award (F99/K00) from the National Cancer Institute of the National Institutes of Health, Liu will be able to continue to advance her research into how cancers avoid treatment and contribute to the development of more effective therapies.  

In this Q&A, Liu shares more about her research, how this award will support her work and how her findings may help shape the future of cancer treatment.

What is the big problem you’re trying to solve with your research?

YL: Cancer therapies that target DNA methylation — chemical marks that silence genes — have been approved for blood cancers, but they haven’t worked well in solid tumors like colon cancer. My research addresses why these medications are less effective in solid tumors.

I discovered that when DNA methylation is blocked, cancer cells switch on a backup system that keeps certain genes turned “off.” This backup system prevents tumor-suppressing genes from turning “on”, which can make treatments that target DNA methylation less effective.

The big problem I’m trying to solve is how to block this resistance mechanism so that epigenetic therapies can work better in solid tumors and, ultimately, improve patient outcomes.

How will this award help you address your research question?

YL: This award will support my transition from a Ph.D. student to a postdoctoral researcher. As a Ph.D. student, I’ll test whether combining drugs that target DNA methylation with new strategies that block cancer cells’ backup system can boost tumor suppression and help the immune system better attack cancer. This builds directly on my previously published work, which identified an epigenetic vulnerability in cancer’s defenses.

As a postdoctoral fellow, I’ll expand my research into immuno-oncology — cancer treatment that harnesses the immune system to fight cancer — by focusing on how epigenetic regulation affects CAR T cell therapy in solid tumors. CAR T therapies are relatively new treatments that train a person’s own immune cells to fight certain cancers. They are extremely promising but, as of now, are limited to treating multiple myeloma and some leukemias and lymphomas.

The award provides me with the resources, mentorship and protected time to tackle these high-risk, high-impact questions and to build the skills I’ll need for an independent research career.

What is the most exciting thing about your research?

YL: For me, the most exciting part is uncovering hidden layers of how cancer cells adapt to therapy. We found that when DNA loses its usual chemical tags, it unexpectedly sets off a chain reaction that strengthens gene silencing instead of reversing it.

By targeting this process, we hope to improve the effectiveness of existing drugs while also opening the door to combining epigenetic therapy with immunotherapy. Looking ahead, I’m excited to apply these concepts to engineer better CAR T cells for treating solid tumors — an area where there is a tremendous unmet need.

It’s rewarding to know that our work at the molecular level could translate into new strategies for patients who currently have limited treatment options.

Funding Acknowledgement

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award no. F99CA305570 (Liu). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.