The main goal of the Chavez laboratory is the molecular characterization of childhood cancers in order to find drug targets and improve treatment options. Our main focus is on pediatric brain tumors such as medulloblastoma, glioblastoma, and ependymoma.
Structural variants (SVs) as well as circular extrachromosomal DNA (ecDNA) are known drivers of aggressive tumor growth by promoting oncogenic fusion genes and high oncogene copy number. Analysis of the effects of SVs on the gene regulatory landscape of tumor genomes as well as profiling the frequency and diversity of ecDNA in the different types of pediatric brain tumors are currently the main research areas in the Chavez lab. In addition, we leverage epigenetic information such as DNA methylation and enhancer profiling in pediatric brain tumors and normal human tissues to identify clinically relevant tumor subgroups, oncogenic enhancers, transcription factors, and pathways amenable to pharmacologic targeting. By integrating heterogeneous data types and genetic and pharmacological inhibition experiments, we analyze oncogenic mechanisms and novel tumor-dependency genes and pathways that may provide new targets for improved therapeutic approaches. The lab also develops and applies new statistical and machine learning tools for the quantitative and integrative analysis of genetic, epigenetic, and imaging data.
The Pediatric Neuro-Oncology Molecular Tumor Board (MTB) at Rady Children’s Hospital was created in 2017 and consists of physician-scientists, clinicians, and researchers in the field of tumor genetics. The board recommends advanced testing, including rapid whole genome sequencing, for some children with tumors in the brain or spinal cord.
Under the scientific direction of Dr. Chavez, members of the tumor board examine the results of these tests and attempt to identify mutations and signaling pathways involved in tumor growth. In addition, the tumor board coordinates drug screening on living tumor cells to evaluate the efficacy of various drugs and drug classes in reducing tumor cell viability. Specific short- and long-term goals include further developing platforms for studying the genetics of tumors, patients, and families, conducting monthly MTB meetings to discuss the results of genetic and functional drug screening in a clinical context, and continuing to expand the biorepository of tumor biopsy samples and patient models for advanced molecular characterization and targeted drug testing.