Grad Student Breaking New Ground in Glioblastoma
April 4, 2017 | by Samantha Bonar
Cui came to the Irell & Manella Graduate School of Biological Sciences at City of Hope in August 2011, right after receiving his Bachelor of Science in biological technology from Nankai University in China. He says he chose the Ph.D. program at City of Hope “because of the excellent cancer research and translational research going on here.”
Working alongside Yanhong Shi, Ph.D., professor and director of the Division of Stem Cell Biology Research at Beckman Research Institute of City of Hope, Cui’s current research focuses on the brain tumor glioblastoma, the most common and aggressive primary brain tumor in adults. While glioblastoma tumors are rare, the tumor cells grow and spread quickly, have a nearly 100 percent recurrence rate and are very challenging to treat due to their location deep in the brain.
“I am trying to understand the biology and mechanism of tumor progression and aim to develop novel therapeutics for this tumor,” Cui said.
In a just-published study, Cui, Shi and colleagues found that a specific RNA modification, called m6A RNA methylation, would be a novel target for treating glioblastoma by regulating the behavior of glioblastoma stem cells.
“This small cell population within the tumor is believed to be able to give rise to the tumor and render glioblastoma treatment-resistant and recurring,” Cui said.
Cui and his associates identified a small compound that can modulate m6A RNA modification and inhibit tumor growth originated by glioblastoma stem cells in a mouse model.
The study, co-authored with collaborators from the University of Chicago and the Shanghai Institute of Materia Medica, was published in the March 14 issue of the prestigious peer-reviewed journal Cell Reports as “m6A RNA Methylation Regulates the Self-Renewal and Tumorigenesis of Glioblastoma Stem Cells.”
The researchers found that m6A RNA methylation regulates tumor production through targeting cancer stem cells, and that a small molecule inhibitor of the fat-mass and obesity-associated gene called FTO suppresses glioblastoma progression and prolongs lifespan of tumor-bearing animals, presumably by maintaining the m6A methylation modification. Their work indicates that m6A modification plays a critical role in regulating glioblastoma stem cells that novel cancer therapies should aim to target.
The study demonstrates important roles for m6A in regulating multiple types of cancers, such as glioblastoma and leukemia, suggesting that targeting m6A modification machinery can be a general therapeutic tool for a variety of cancers.
This is Cui’s sixth published study since joining City of Hope in 2012. Previous research has focused on downregulation of TLX in inducing TET3 expression and inhibiting glioblastoma stem cell self-renewal and tumorigenesis; TLX-miR-219 cascade regulating neural stem cell proliferation in neurodevelopment and schizophrenia iPSC model; nuclear receptor TLX in development and diseases; adaptive amphiphilic dendrimer-based nanoassemblies as robust and versatile siRNA delivery systems; and the molecular basis for improved gene silencing by Dicer substrate interfering RNA compared with other siRNA variants. He has also presented work on treatments for lymphoma and glioblastoma.
Cui hopes to continue academic study as a postdoc fellow at City of Hope. After that, he plans to go back to China to have his own lab “and continue academic discovery” in the field of oncology.
“I will study these issues for my career,” he said. “The importance of these issues for the health of society, and the needs for scientific discovery in this field, are what make me feel that I would like to devote my efforts in this area.”