Normal Growth Control and Tumor Formation in the Mammalian Brain
The development of the mammalian brain is a highly regulated process involving both cell-autonomous and non-cell-autonomous decisions that determine cell fate, proliferation, migration and death. The genes that govern these critical decisions are often mutated in human cancers, and their de-regulated function in the central nervous system (CNS) leads to the development of brain tumors. Our laboratory is interested in understanding the key signals that control normal neural stem cell (NSC) and glial cell growth and differentiation in vitro and in vivo. To this end, we study the genes mutated in the two cancer predisposition syndromes, neurofibromatosis 1 (NF1) and neurofibromatosis 2 (NF2), in which affected individuals develop brain tumors. We have generated numerous genetically-engineered mouse models to explore the relationship between developmental neurobiology (normal growth regulation in the brain) and neuro-oncology (brain tumor formation).
Lee DY, Gianino SM, Gutmann DH: Innate neural stem cell heterogeneity determines the patterning of glioma formation in children. Cancer Cell (in press).
Banerjee S, Crouse NR, Emnett RJ, Gianino SM, Gutmann DH: Neurofibromatosis-1 regulates mTOR-mediated astrocyte growth and glioma formation in a TSC/Rheb-independent manner. Proc Natl Acad Sci USA 108:15996-6001, 2011.
Lee DY, Yeh T-H, Emnett RJ, White CR, Gutmann DH: Neurofibromatosis-1 regulates neuroglial progenitor proliferation and glial differentiation in a brain region-specific manner. Genes & Development 24:2317-29, 2010.
Houshmandi SS, Emnett RJ, Giovannini M, Gutmann DH: The neurofibromatosis-2 protein, merlin, regulates glial cell growth in an ErbB2- and Src-dependent manner. Mol Cell Biol. 29:1472-86, 2009.
Hegedus B, Dasgupta B, Shin JE, Emnett RJ, Hart-Mahon EK, Elghazi L, Bernal-Mizrachi E, Gutmann DH: Neurofibromatosis-1 regulates neuronal and glial cell differentiation from neuroglial progenitors in vivo by both cAMP- and Ras-dependent mechanisms. Cell Stem Cell 1:443-457, 2007.
Dr. Gutmann's Contact Information
David H. Gutmann, MD, PhD
Donald O. Schnuck Family Professor
© 2006-2012 Washington University School of Medicine