SCIENCE
Our overarching research vision is to identify and characterize drivers of pediatric cancers, delineating tumor evolution and defining the mechanisms by which a normal cell transforms into a cancer cell. We use a toolbox of approaches including molecular neurobiology, genetics, cancer genomics, developmental neuroscience, epigenetics, and proteomics. Our ultimate goal is to leverage mechanistic insights to identify novel therapeutic targets and inform therapeutic approaches to improve outcomes for childhood cancer.
Mechanisms of oncogenesis in FOXR2-expressing cancers
We use functional genomic approaches to understand how the oncogene FOXR2 is activated in pediatric brain tumors as well as other adult and pediatric cancers. FOXR2 is aberrantly activated in nearly 10% of all cancers. If we can better understand the mechanisms by which its expression leads to tumor formation, we could potentially find new therapeutic vulnerabilities for the most devastating pediatric brain tumors.
Understanding the role of oncogenes in normal development
Pediatric cancers are distinct from adult cancers as they often arise through aberrant development. We are interested in understanding what the role of oncogenes are during normal development, how they are regulated, and how development can go awry to cause tumor formation.
Harnessing high-throughput genomic assays to identify dependencies and downstream mediators
Genetic dependencies in cancer cells are genes that, when knocked out, are required for cell survival. We harness the power of high-throughput genomic assays to systematically map the dependencies of cancer cells. We also utilize these approaches to identify mediators of cancer cell proliferation. We have a wide interest in utilizing genetic perturbation approaches to ask unique interdisciplinary questions, and we collaborate with multi-disciplinary teams including mathematicians, computer scientists, neuroscientists, and nanotechnology engineers.
Creating and characterizing new pediatric cancer models
We are incredibly lucky to work at Children’s Hospital Los Angeles where we have patients, families, and oncologists who are willing to provide us with tumor tissue. We are able to make cancer cell lines from these primary tumors that we can then use to study the biology of pediatric brain and solid tumors. We characterize these models using genomic and transcriptomic approaches, and also study how these cells respond to new candidate drugs and chemotherapy combinations. Ultimately, our goal is to share these tremendously valuable cell lines with the pediatric oncology research community in hopes that we can accelerate new discoveries and therapies.