Gutmann Laboratory

David H. Gutmann, MD, PhD

Normal Growth Control and Tumor Formation in the Mammalian Brain

Overview

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).

Recent Publications:

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 Dev. 2010 Oct 15;24(20):2317-29. Epub 2010 Sep 28

Brown JA, Gianino SM, Gutmann DH. Defective cyclic AMP generation underlies the sensitivity of central nervous system neurons to neurofibromatosis-1 heterozygosity. J Neurosci 2010 30:5579-89.

Banerjee S, Byrd JN, Gianino SM, Harpstrite SE, Rodriguez FJ, Tuskan RG, Reilly KM, Piwnica-Worms DR, Gutmann DH. Neurofibromin controls cell growth by regulating STAT3 activity in vitro and in vivo. Cancer Res 2010 70:1356-66.

Cui Y, Costa RM, Murphy GG, Elgersma Y, Zhu Y, Gutmann DH, Parada LF, Mody I, Silva AJ. Neurofibromin regulation of ERK signaling modulates GABA release and learning. Cell 2008 135:549-560.

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 2007 1:443-457 [cover feature].

Laboratory Web Page

2011 Neuro Oncology Research Group Seminar Series

NF Center