Growth Regulation in the Nervous System
The development of targeted therapies for brain tumors in children and adults requires a detailed understanding of the growth control pathways that govern cell expansion in the nervous system.
Using NF1 as a genetic model, we have demonstrated that neural stem cells and astrocytes from different regions of the brain are molecularly distinct, and respond differentially to Nf1 gene inactivation. Moreover, the manner in which tumor suppressor proteins function is not only cell type- and brain region-specific, but is also governed by the specific growth-promoting signals (e.g., chemokine, growth factor) and the genomic background (mouse strain). This concept of “contextual signaling” is critically important to designing effective therapies for diseases caused by mutations in tumor suppressor genes, like NF1.
Current projects in the Gutmann research laboratory are focused on understanding the molecular mechanisms by which RAS activation as a consequence of loss of NF1 protein (neurofibromin) expression dictates astrocyte, neuron and neural stem cell biology using this contextual signaling framework. In addition, we are examining the composition and function of the mechanistic target of rapamycin (mTOR) complex in brain cells.