David H. Gutmann, M.D., Ph.D.
Donald O. Schnuck Family Professor
Neurology
Vice Chair for Research Affairs
Neurosciences Program
Cancer Biology Program
Molecular Genetics and Genomics Program
Developmental, Regenerative and Stem Cell Biology Program
314-362-7379
314-362-1151
314-362-2388
8111
2208 McMillan Building
gutmannd@wustl.edu
https://gutmannlab.wustl.edu/
@GutmannLab
pediatric brain cancer, brain development, neuroimmunology, cancer neuroscience, autism, hiPSCs, genetically engineered mice
Leveraging neurogenetic disorders to study normal brain development, cancer, and autism
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)
> Delineating how immune system-like cells (microglia) dictate brain tumor development and neuronal dysfunction (neuroimmunology)
> Determining the molecular and cellular mechanisms underlying neuronal control of nervous system tumor formation and growth (cancer neuroscience)
> 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
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).
Mentorship and Commitment to Diversity Statement:
In our laboratory, we are firmed committed to mentoring trainees at all levels and fostering diversity.
Selected Publications:
Pan Y, Hysinger JD, Barron T, Schindler NF, Cobb O, Guo X, Yalçın B, Anastasaki C, Mulinyawe SB, Ponnuswami A, Scheaffer S, Ma Y, Chang KC, Xia X, Toonen JA, Lennon JJ, Gibson EM, Huguenard JR, Liau LM, Goldberg JL, Monje M, Gutmann DH. NF1 mutation drives neuronal activity-dependent initiation of optic glioma. Nature 594(7862):277-282, 2021. PMID: 34040258
Wegscheid ML, Anastasaki C, Hartigan KA, Cobb OM, Papke JB, Traber JN, Morris SM, Gutmann DH. Patient-derived iPSC-cerebral organoid modeling of the 17q11.2 microdeletion syndrome establishes CRLF3 as a critical regulator of neurogenesis. Cell Reports 36(1):109315, 2021. PMID: 34233200
Mo J, Anastasaki C, Chen Z, Shipman T, Papke J, Yin K, Gutmann DH, Le LQ. Humanized neurofibroma model from induced pluripotent stem cells delineates tumor pathogenesis and developmental origins. J Clin Invest. 131(1):e139807, 2021. PMID: 33108355
Guo X, Pan Y, Xiong M, Sanapala S, Anastasaki C, Cobb O, Dahiya S, Gutmann DH: Midkine activation of CD8+ cells establishes a neuron-immune-cancer axis responsible for low-grade glioma growth. Nat Commun 11: 2177, 2020. PMID: 32358581
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
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
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: 10/31/2021 9:04:48 AM
Abnormal differentiation of neural stem cells