Department of Pharmacology
and Chemical Biology
Read Lab
High grade gliomas (HGGs), the most common primary brain tumors, are caused by mutations that perturb developmental and homeostatic processes in glial progenitor cells and/or neural stem cells in the central nervous system (CNS). Our goal is to determine how aspects of HGG cell biology and genetics can be effectively targeted to actively eliminate these tumor cells in the brain. To this end, our research addresses a number of outstanding questions in the field. For example, how do mutations in cell signaling pathways promote malignancy? How are other pathways or mutations involved in HGG? Which genes specifically control HGG cell invasion? Which glial cells and/or neural stem cell types in the CNS undergo neoplastic transformation and why? How do cell-cell interactions in the brain contribute to HGG tumorigenesis? Can the molecular pathways driving HGG be effectively targeted for therapeutic benefit?
Glioblastoma
Research Program
Our research program uses a multidisciplinary approach to analyze the function of developmental cell-signaling pathways in tumorigenesis. Our research projects now focus all on mammalian brain tumor model systems, including mouse genetic models of HGG, primary patient-derived human HGG stem cells, and human iPS cell-derived brain organoid ('mini-brain') models. Previous projects in our lab used Drosophila melanogaster HGG models. Our current projects focus on the functional role of mutant variants' in receptor tyrosine kinases (RTKs), such as EGFR and MET, and their downstream signaling pathways in tumor initiation and progression.
Through our efforts, we identified new RTK effectors that regulate tumor cell proliferation and invasion as well as tumor-microenvironment interactions. Our work includes new clinical trials that target effectors of RTK signaling in HGG, including the YAP and TAZ transcription factors. Ongoing projects in our lab include research on the role of RTK effector pathways in tumor development and the role of other secreted factors in cell-cell interactions in the tumor microenvironment.
Our research program is aided by productive collaborations with other neuro-oncology researchers in the Departments of Neurosurgery, Pediatrics, Human Genetics, Pathology, and Hematology and Medical Oncology, including clinical neurosurgical and neuropathology faculty. We welcome young scientists who seek to enter this dynamic field. Trainees in our lab will have opportunities to work with all of our brain tumor model systems, perform drug testing experiments in pre-clinical paradigms, interface with clinical neuro-oncology faculty, and advocate for patient outreach and education.
