David H Gutmann, MD, PhD

Donald O. Schnuck Family Professor of Neurology

Using mouse models to understand normal brain and brain tumor development Read More

Email: gutmannd@wustl.edu
Lab Phone: (314) 362-1151
Website: Gutmann Lab
Lab Location: 2208 McMillan Building
Keywords: brain cancer, brain development, neurons, neural stem cells, glia, genetically-engineered mouse models, learning and behavior, iPSCs, signal transduction, sexual dimorphism

Using mouse models to understand normal brain and brain tumor development

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 neurogenetic conditions. One of the most common of these disorders is neurofibromatosis type 1 (NF1).

Using NF1 as a model genetic system to understand normal growth and differentiation in the normal brain, our laboratory aims to characterize the genetic, cellular, and molecular factors that contribute to the development of nervous system tumors (gliomas and neurofibromas) and cognitive problems (learning and attention deficits). Defining these contributing factors represents the first step toward establishing new treatments for children and adults with NF1. Moreover, NF1 provides unique opportunities to unravel the complexities of related medical problems in the general population, including adult and childhood brain tumors, breast cancer, and autism.

We employ these single gene disorders as model genetic platforms to understand how genomic, tissue, cellular and molecular factors control normal neural stem cell, neuron and glial function in vitro and in vivo. To accomplish these goals, we have generated numerous genetically-engineered mouse models and human induced pluripotent stem cell lines.

Current research in our laboratory includes:

• The impact of Ras signaling, mammalian target of rapamycin (mTOR) activity, and intracellular cyclic AMP generation in specifying cell proliferation, cell death, and differentiation in the brain

• The instructive role of the tumor microenvironment, specifically microglia (macrophage-like cells), in dictating brain tumor formation and growth

• The diversity of neural stem cell function as defined by the brain region of origin

• The relationship between brain region-specific neural stem cells and cancer development in children and adults

• The molecular and genomic determinants that underlie cognitive and behavioral dysfunction in neurons

Updated October 2016

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