Mai Dang, MD, PhD
Assistant Professor, Department of Neurology, University of Washington in St. Louis School of Medicine
Modulating Microglia to Enhance Pediatric Brain Tumor Treatment
can drugs be used to make microglia more effective in consuming damaged brain cancer cells, thus making us better at treating pediatric brain cancers?
Dr. Dang is a neurologist interested in better understanding and treating pediatric brain tumors. Currently, doctors know very little about the abundance of myeloid cells, including monocyte-derived macrophages and brain resident microglia, that infiltrate medulloblastoma (MB), the most common malignant pediatric brain tumor. With her Young Investigator Award, Dr. Dang plans to focus on microglia, the resident immune cells of the brain. Microglia have strong phagocytic capacity, meaning that they have the ability to consume damaged and dying cells, a capability that doctors might hope to leverage so that microglia could be caused to consume more tumor cells damaged by treatment, promoting greater tumor shrinkage and improving survival.
Dr. Dang’s lab has already shown that when the drug vismodegib is used to inhibit SHH (sonic hedgehog protein, necessary for brain development,) the brain tumor environment is enriched with microglia. Building on this finding, Dr. Dang hopes to prove that using this drug to inhibit SHH will result in more microglia in the tumor environment and will produce more robust microglia that is more phagocytic, meaning that it will ingest more tumor cells damaged by drug therapy, thereby improving survival in MB. She will first determine the role of the SHH pathway in regulating microglia proliferation and phagocytic activity and then further investigate if inhibition of SHH can be used to shrink tumors and extend survival. If her suppositions are correct, she will have uncovered an innovative adjunctive therapy that could make chemotherapy more effective in treating medulloblastoma and potentially other brain cancers.