Assistant Professor, Biochemistry and Molecular Genetics
My research goal is to utilize orthogonal genomic data to discover novel cancer drivers and understand their function and underlying mechanism. His group is interested in combining computation and experimental approaches (especially high-throughput sequencing) to understand the regulation and functional consequence of somatic mutations in cancer.
Identify Novel Therapeutic Targets and Biomarkers in Non-coding Genome of Pediatric Cancers
Transcription factors are proteins that control the rate of transcription, the process by which information from DNA is copied into a new molecule of RNA. Transcription factor FoxM1 has been found to play a role in the growth of glioblastoma and researchers seek to better understand this connection in the pursuit of targeted therapies.
All Brain Tumor Types, (AT/RT)
Atypical Teratoid/Rhabdoid Tumor
Central nervous system (CNS) atypical teratoid/rhabdoid tumor (AT/RT) is a very rare, fast-growing tumor of the brain and spinal cord. It usually occurs in children aged three years and younger, although it can occur in older children and adults. About half of these tumors form in the cerebellum or
Tracing Evolution History of 100 Whole Genome Sequences of Diffuse Stem Brain Tumor
Diffuse intrinsic pontine glioma (DIPG) is a deadly disease among young children. The evolution path and mutational processes giving rise to DIPG remain elusive. We analyzed 100 whole genome sequences (WGS) from 60 DIPG patients. This revealed 25% DIPGs acquired whole-genome duplications (WGD) early during tumor evolution. WGD samples are associated with loss of TP53 and poorer survival. In addition, almost all WGD samplers harbor complex structural variations (SVs) and show characteristic short microhomology at SV breakpoints. Mutation analysis revealed that H3K27M driver mutation is acquired early during tumor clonal evolution. Mutation signature analysis identified a unique mutational process at a late stage of tumor evolution. This study revealed that tumor evolution of DIPG is characterized by chromosomal instability shaped by DNA repair defects and dynamic mutational processes. Our work shed new insights on the disease pathogenesis of DIPG and provided rationale for designing novel therapy for this deadly disease.
Recurrent Structural Variations of lncRNA Gene CCDC26 in diffuse intrinsic pontine glioma
We report recurrent somatic structural variations (SVs) involving long noncoding RNA (lncRNA) CCDC26 in 13% of Diffuse Intrinsic Pontine Glioma (DIPG) patients. We validate our findings using whole genome sequencing data from two independent patient cohorts. CCDC26 SVs cause increased expression of
Lihua Zou, PhD