David H Gutmann
Washington University in St Louis, MO·Neuroscience
Neurofibromatosis type 1 (NF1) is a rare inherited condition caused by mutations in the NF1 gene. It is easy to diagnose but hard to predict.
- Fields
Neuroscience
Medicine & Clinical Research
Genetics
- Topics
neurofibromatosis type 1
low-grade glioma
optic pathway glioma
- Grants
- 2 known grants, through Apr 2033
What they work on
- Define the cellular and molecular interdependencies, among tumor cells, neurons, T cells and microglia, that drive NF1-associated low-grade glioma and neurodevelopmental deficits, using patient and CRISPR-engineered iPSCs and Nf1 mutant mice.
- Determine how risk factors modify these multicellular circuits to create the clinical variability of NF1, using mice with patient-derived NF1 mutations, cell type-specific Nf1 knockouts and multi-omic analysis.
- Define the immune cell composition of Nf1 optic pathway gliomas in mice to map which immune cells populate these slow-growing brain tumors.
- Determine why CD8+ T cells, killer immune cells, are selectively recruited into mouse Nf1 optic gliomas, and how NF1 mutation in neurons alters T cell–microglia interactions that support tumor growth.
More about the research
Some children develop learning and behavior problems, and others develop low-grade gliomas (LGGs), slow-growing brain tumors that can threaten vision when they form along the optic nerve. Current drugs aim at single cell types or single signaling pathways and help only some patients. The work rests on the idea that these problems arise from conversations among many cell types: tumor cells, neurons, immune T cells and microglia, the brain's resident immune cells. Two projects map these multicellular circuits, one broadly across NF1 and one focused on a particular immune cell in brain tumors.
Why it matters
Children with NF1 face unpredictable brain tumors that can cause vision loss, as well as cognitive and behavioral problems, and current treatments work for only some of them. Mapping the cell-to-cell circuits behind these problems could help doctors predict which children are at risk. It could also point to new immune-based treatments for low-grade gliomas, and provide a model for other neurogenetic disorders.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Yunshuo Tang
Washington University in St Louis, MO·Neuroscience·Early-career
Define whether estrogen-induced production of interleukin 1 beta, an inflammatory signal made by glial support cells, is required for retinal ganglion cell death in authenticated mouse models of Nf1 optic pathway glioma.
Luis Parada
Indiana University-Purdue University-Indianapolis, IN·Medicine & Clinical Research
Test whether NF1-mutant glioblastomas have distinct tumor cell properties and immune microenvironments, using engineered mice lacking NF1, Tp53 and Pten compared with NF1-normal QKi/Tp53/Pten mice.
Dolores Hambardzumyan
University of Pennsylvania, PA·Microbiology & Immunology
Map how glioblastoma subtype and location shape monocyte and neutrophil infiltration, using single-cell RNA sequencing, spatial multiomics and multiplex flow cytometry in mice carrying human tumor-driving mutations.
The school
Washington University in St Louis: 97 labs on PI Pages, $1.2B a year on research, 365 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.