Alum Profile: Xu Liu wants to make better cancer treatments by harnessing autophagy
As a senior scientist in oncology research and development at AstraZeneca, Xu Liu strives to make cancer drugs safer and more tolerable. But this patient-focused work has its roots in the fundamental science of a cellular process that sparked his curiosity more than a decade ago.
One day in 2010, while studying as an undergraduate at Wuhan University in China, Liu found himself engrossed in an article in Scientific American. The topic was autophagy, a metabolic process somewhat akin to an intracellular recycling station. Little did the young biology major realize at the time, the article’s author would eventually help launch Liu’s career as a scientist.
Autophagy — from the Greek words auto- (“self ”) and phagein (“to eat”) — degrades and recycles cellular components to protect cells from stress, starvation and infection. Liu read about how disruptions to this process can lead to diseases such as neurodegeneration and diabetes, whereas cancer cells can co-opt autophagy to resist treatment and promote recurrence.
"Now, that’s interesting," he thought. What if there is a way to safely modulate autophagy activity for therapeutic purposes?
Chance meetings and a choice mentorship
With his bachelor’s degree from one of the most prestigious biology programs in China in hand, Liu set out to pursue this path of inquiry. As he explored options for graduate studies in the United States, the University of Michigan — with its world-renowned biomedical research programs, expert faculty and large international community — rose to the top of his list.
“I thought I would get a unique experience exposed to different cultures, making friends with people from all over the world while working with world-class scientists,” Liu explains.
As chance would have it, the graduate admissions advisory committee member who interviewed Liu was Daniel Klionsky, a faculty member at the U-M Life Sciences Institute and the author of the Scientific American article that had captured Liu’s interest. Klionsky recommended Liu for admission to the Molecular, Cellular, and Developmental Biology Ph.D. program and ultimately offered Liu a position in his lab at the LSI.
In the Klionsky lab, where he was known for his kind and generous personality and collaborative nature, Liu studied the molecular mechanisms that drive autophagy and its regulation under different stress conditions. Among Liu’s stand-out scientific contributions, Klionsky says, is the first study to show that a naturally occurring mutation in the key autophagy gene ATG5 is associated with ataxia, a neurodevelopmental disease.
“Xu was a fantastic student and postdoc — technically skilled, but also willing to try and develop new experimental approaches, at which he was usually successful,” Klionsky recalls. “In fact, Xu worked out the procedure for RNA immunoprecipitation, which has become an important technique in my lab. He played a critical role in developing my lab’s interest in post- transcriptional regulation of autophagy.”
Autophagy applied, from organoids to oncology
While he enjoyed studying the basic science of autophagy and his projects at the LSI, Liu says he was eager to see this work applied more directly to human physiology and disease. After completing his Ph.D. and early postdoctoral work at U-M, he joined the lab of Matthew Waldor at Harvard Medical School.
As a postdoctoral researcher, Liu investigated the role of autophagy in infection and the mechanisms by which disease-causing pathogens infect cells lining the gastrointestinal tract. He developed small intestine and colon organoids (three-dimensional cell cultures that more closely resemble human tissue) to better understand the signaling pathways that regulate pathogen infection.
My hope is to continue to grow as a scientist and apply my expertise to help develop better therapeutics for patients with unmet medical needs.
Throughout his graduate and postdoctoral work, Liu vacillated between whether to pursue an academic research career or one in the biomedical industry. He recalls many talks with Klionsky, who helped him navigate his options.
“I am so grateful for having Dan as my mentor,” Liu says. “I got state-of-the-art training from one of the pioneers in the autophagy field and enjoyed the freedom to explore projects, with Dan always available to discuss and provide insightful suggestions. He is not just a great scientist who tries to help students become independent biologists, but he really cares about his students’ career development.”
Determined to pursue research that more directly applies to human health, Liu turned to the biomedical industry for his next step and joined AstraZeneca in 2020.
Now, he leverages his knowledge of the fundamental biology of autophagy and infection to develop better cancer drugs. He supports the oncology therapeutic pipeline by assessing and predicting drug-induced gastrointestinal toxicity.
“My hope is to continue to grow as a scientist and apply my expertise to help develop better therapeutics for patients with unmet medical needs,” Liu says. “In recent years, autophagy has attracted much attention in the pharmaceutical industry. My ultimate goal is to harness autophagy to treat human disease.”