David H. Gutmann is the Donald O. Schnuck Family Professor of Neurology, Co-director of the Neuro-Oncology Program in the Washington University/Alvin J. Siteman Cancer Center, and Director of the Neurofibromatosis Center at Washington University.

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).

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.

Selected Publications

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 (in press).

Tang X, Jang S-W, Wang X, Liu Z, Bahr SM, Sun S-Y, Brat D, Gutmann DH, Ye K. Akt phosphorylation regulates merlin tumor suppressor activity by mediating merlin ubiquitination and degradation. Nature Cell Biology (in press).

Daginakatte GC, Gutmann DH. Neurofibromatosis-1 (Nf1) heterozygous brain microglia elaborate paracrine factors that promote Nf1-deficient astrocyte and glioma growth. Hum Mol Genetics 2007 16:1098-1112.

Sandsmark DK, Zhang H, Hegedus B, Pelletier CL, Weber JD, Gutmann DH. Nucleophosmin mediates mammalian target of rapamycin-dependent actin cytoskeleton dynamics and proliferation in neurofibromin-deficient astrocytes. Cancer Res 2007 67:4790-4799.

Sharma MK, Mansur DB, Reifenberger G, Perry A, Leonard JR, Aldape KD, Albin MG, Emnett RJ, Loeser S, Watson MA, Nagarajan R, Gutmann DH. Distinct genetic signatures among pilocytic astrocytomas related to their brain region origin. Cancer Res 2007 67:890-900.