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David H. Gutmann, MD, PhD

David H. Gutmann is the Donald O. Schnuck Family Professor of Neurology and Director of the Washington University Neurofibromatosis (NF) Center (http://nfcenter.wustl.edu).

Laboratory Research. 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 as well as cognitive and behavioral deficits. Our laboratory is interested in understanding the key signals that control normal neural stem cell (NSC), neuronal function, 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 nervous system tumors as well as cognitive and behavioral problems. We have generated numerous genetically-engineered mouse models to explore the relationship between developmental neurobiology (normal growth regulation in the brain), neuronal function (learning, memory, and attention), and neuro-oncology (brain tumor formation).

Clinical/Translational Research. NF1 represents an ideal genetic model system to understand the numerous factors that contribute to neurological disease heterogeneity. Using novel enabling resources developed in the Washington University NF Center, including the NF1 Genome Project, the NF1 Patient Registry Initiative, and the NF1 Induced Pluripotent Stem Cell Study, we are working to critically define the basis for clinical heterogeneity as an initial step toward personalized (precision) medicine.

Medical Training

Dr. Gutmann received his M.S. in Human Genetics, Ph.D. in Microbiology and Immunology, and M.D. from The University of Michigan prior to completing residency training in Neurology at The University of Pennsylvania and postdoctoral fellowship training in Molecular Medicine and Genetics in the laboratory of Dr. Francis Collins.

Select Publications

Diggs-Andrews KA, Brown JA, Gianino SM, Rubin JB, Wozniak DF, Gutmann DH. Sex is a major determinant of neuronal dysfunction in neurofibromatosis type 1. Ann Neurol. (in press).

Diggs-Andrews KA, Tokua K, Izumi I, Zorumski CF, Wozniak DF, and Gutmann DH. Dopamine deficiency underlies learning deficits in neurofibromatosis-1 mice. Ann Neurol. 73:309-15, 2013.

Pong WW, Higer SB, Gianino SM, Emnett RJ, Gutmann DH. Reduced microglial CX3CR1 expression delays neurofibromatosis-1 glioma formation. Ann Neurol. 73: 303-8, 2013.

Kaul A, Chen Y-H, Emnett RJ, Dahiya S, and 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

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

Banerjee S, Crouse NR, Emnett RJ, Gianino SM, and 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, and Gutmann DH. Neurofibromatosis-1 regulates neuroglial progenitor proliferation and glial differentiation in a brain region-specific manner. Genes & Development 24:2317-29, 2010.