Published Sunday 11 July 2021, 12:04 pm
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Each year, 790 Americans are diagnosed with a rare and deadly form of brain cancer called a diffuse midline glioma, according to the National Cancer Institute. Tragically, only 2 percent of children with this disease will survive for five years.
Jia-Ray Yu, a new assistant professor who joins the Fralin Biomedical Research Institute at VTC and the Department of Biomedical Sciences and Pathobiology on Sept. 1, is studying these fast-growing, treatment-resistant brain tumors, which often affect children, in hopes of identifying new therapeutic approaches.
Yu will be the first of several cancer researchers to work at Virginia Tech’s brand new research facility at the Children’s National Research & Innovation Campus in Washington, D.C.
“This disease is fatal and there is no cure. Any hint of a potential therapeutic path could be helpful,” said Yu, who will also hold an adjunct faculty position at the Children’s National Hospital Center for Cancer and Immunology Research.
Michael Friedlander, Virginia Tech vice president of health sciences and technology and executive director of the Fralin Biomedical Research Institute, led Yu’s recruiting.
“Jia-Ray Yu is one of the emerging leaders in understanding the molecular substrates of aggressive childhood brain cancers that can help identify innovative therapeutic approaches. In addition, his fundamental research on chromatin remodeling is at the forefront of this area of emerging field interest in molecular biology,” Friedlander said. “We are fortunate to have Dr. Yu to Virginia Tech as we grow our larger cancer research community and our partnership with one of the nation’s leading pediatric health care and research systems, Children’s National Hospital.”
Yu studies how genes change when an ordinary brain cell develops malignant traits.
In particular, he is investigating changes in proteins called histones, which wind up strands of DNA molecules into a substance called chromatin, which forms chromosomes. In addition to packing genetic material into cells, these structures also play a key role in telling genes when to turn them on or off.
Defective histone proteins alter the structure of the chromatin, which in turn distorts the genetic instructions that regulate a cell’s behavior, growth rate and identity. Moreover, when this defective cell divides, its two daughter cells inherit the chromatin from the original cell, the malignant properties are passed on, and the cancer grows.
“These epigenetic features of chromatin are different from the DNA itself, but they are inherited during cell division,” Yu said.
Eighty percent of tumors of diffuse midline gliomas start with a single cell with a histone gene defect, said Yu, who found that when this small piece of a specific histone, called H3K27, stops working properly, it creates a series of domino-like reactions that cause normal cells to become cancerous.
Yu recently explored this molecular cascade as a postdoctoral researcher in the lab of Danny Reinberg, Terry and Mel Karmazin Professor in the NYU Grossman School of Medicine Department of Biochemistry and Molecular Pharmacology, and senior Howard Hughes Medical Institute Investigator.
The research team identified two genes, NSD1 and NSD2, which appear to be the molecular fingers that tap the histone domino. When these genes are turned off, diffuse midline gliomas stop growing in a cultured lab dish and in animal models. They also identified signaling pathways that could be targets for new drug therapies. Their findings are available in pre-print and will be published this summer in Science Advances.
Yu’s lab at the new Children’s National Research & Innovation Campus in Washington, DC, will build on this fundamental question: How can chromatin-associated molecules be used to stop aggressive cancers?
Yu says that while studying the molecular genesis of diffuse midline glioma, he can also identify therapeutic approaches for other diseases, such as leukemia and Sotos syndrome, involving mutations in these chromatin-associated molecules.
His research team will combine biochemistry, single-molecule imaging, next-generation sequencing, biophysics and preclinical research to develop and test novel pharmaceutical alternatives to chemotherapy and radiation.
Yu was awarded a three-year American Cancer Society Postdoctoral Fellowship while working in Reinberg’s lab.
He completed a bachelor’s degree in biological sciences and technology from National Chiao Tung University in Taiwan, and his PhD in genetics from Stony Brook University and Cold Spring Harbor Laboratory, where he studied signaling pathways in lung adenocarcinoma metastases.
Recruitment for research positions in the Yu lab will begin this summer.