David H. Gutmann, M.D., Ph.D.

Donald O. Schnuck Family Professor
Vice Chair for Research Affairs

Neurosciences Program
Molecular Genetics and Genomics Program
Molecular Cell Biology Program

  • 314-362-7379

  • 314-362-1151

  • 314-362-2388

  • 8111

  • 2208 McMillan Building

  • gutmannd@neuro.wustl.edu

  • https://gutmannlab.wustl.edu/

  • http://nfcenter.wustl.edu/

  • brain cancer, brain development, iPSCs, neural stem cells, glia, genetically-engineered mouse models, learning and behavior, iPSCs, signal transduction, sexual dimorphism

  • Leveraging neurogenetic disorders to study normal brain development, cancer, and behavior

Research Abstract:

Using the common neurogenetic condition, Neurofibromatosis type 1 (NF1) as a model system to understand growth and differentiation in the normal brain, the Gutmann laboratory aims to characterize the genomic, genetic, cellular, and molecular factors that contribute to the development of nervous system tumors (gliomas and neurofibromas), brain development abnormalities, and behavioral 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 and autism.

Current research in our laboratory includes:

Modeling human neurological disease using genetically-engineered mice and human induced pluripotent stem cells (precision medicine)

Defining the role of stem cells in normal brain development and in pediatric brain tumors

Identifying the molecular and cellular basis for sexually-dimorphic disease phenotypes in the brain

Delineating how immune system-like cells (microglia) dictate brain tumor development and neuronal dysfunction

Understanding how abnormal RAS signaling dictates astrocyte, neuron, and neural stem cell biology (contextual signaling)

Determining the molecular and cellular mechanisms underlying neuronal control of nervous system tumor formation and growth

Dr. Gutmann`s work was profiled by the journal Nature Neurology in August 2014 (http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(14)70163-2/fulltext).

Selected Publications:

Pan Y, Xiong M, Chen R, Ma Y, Corman C, Maricos M, Kindler U, Semtner M, Chen Y-H, Dahiya S, Gutmann DH. Athymic mice reveal a requirement for T cell-microglia interactions in establishing a microenvironment supportive for Nf1 low grade glioma growth. Genes Dev 32: 491-496, 2018. PMID: 29632086

Toonen JA, Solga AC, Ma Y, Gutmann DH. Estrogen activation of microglia underlies the sexually-dimorphic differences in Nf1 optic glioma-induced retinal pathology. J Exp Med 214:17-25, 2017. PMID: 27923908

Smithson LJ, Gutmann DH. Proteomic analysis reveals GIT1 as a novel mTOR complex component critical for mediating astrocyte survival. Genes Dev 30:1383-1388, 2016. PMID: 27340174

Chen YH, Gianino SM, Gutmann DH: Neurofibromatosis-1 regulation of neural stem cell proliferation and multi-lineage differentiation operates through distinct RAS effector pathways. Genes and Development 29:1677-1682, 2015. PMID: 26272820

Chen Y-H, D’Agostino McGowan L, Cimino PJ, Dahiya S, Leonard JR, Lee DY, Gutmann DH: Mouse low-grade gliomas contain cancer stem cells with unique molecular and functional properties. Cell Reports 10:1899-1912, 2015. PMID: 25772366

Lee DY, Gianino SM, Gutmann DH: Innate neural stem cell heterogeneity determines the patterning of glioma formation in children. Cancer Cell 22:131-8, 2012. PMID: 22789544

Kaul A, Chen Y-H, Emnett RJ, Dahiya S, Gutmann DH: Pediatric glioma-associated KIAA1549:BRAF expression regulates neuroglial cell growth in a cell type-specific and mTOR-dependent manner. Genes & Development 26:2561-6, 2012. PMID: 23152448

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. PMID: 21896734

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. PMID: 20876733

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. PMID: 18371380

Last Updated: 5/11/2018 9:29:21 AM

Abnormal differentiation of neural stem cells
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