Daniel Brat
Northwestern University, IL·Microbiology & Immunology
Glioblastoma is the most aggressive primary brain tumor, and it grows in a characteristic sequence: a phase before tissue death, a phase in which regions of the tumor die off, and a phase of renewed growth after treatment. When tissue death, or necrosis, sets in, the surrounding neighborhood of cells changes dramatically.
- Fields
Microbiology & Immunology
Medicine & Clinical Research
Neuroscience
- Topics
glioblastoma
brain tumor
tumor microenvironment
- Grants
- 1 known grant, through Mar 2031
What they work on
- Test whether the spatial arrangement of tumor-associated macrophages alongside hypoxic glioma cells in the peri-necrotic niche sustains immune suppression, using an RCAS/tv-a mouse model to follow microenvironment changes after necrosis in real time.
- Determine whether podoplanin displayed by oxygen-starved glioma cells activates the CLEC5A receptor on macrophages and drives an immunosuppressive phenotype through Syk and STAT3 signaling, in patient-derived glioblastoma neurosphere cultures.
- Examine whether hypoxia and TGFβ1 turn on Hippo signaling and podoplanin expression within the peri-necrotic niche, mapping these events with advanced spatial transcriptomics in tumor tissue.
- Test whether Syk inhibitors, added to standard chemoradiation with or without checkpoint inhibitors, reduce immunosuppression, increase CD8+ T cells and prolong survival in preclinical models of primary and recurrent glioblastoma.
More about the research
Large numbers of macrophages, immune cells that normally clear debris and can either attack or shield a tumor, flood in and are pushed into a state that suppresses the immune response. These tumor-associated macrophages come from the region around blood vessels and pile up alongside oxygen-starved tumor cells in the rim surrounding dead tissue. The central hypothesis is that this rim acts like an engine: the physical arrangement of macrophages next to hypoxic glioma cells, and their reliance on each other, keeps immune suppression running.
Why it matters
Glioblastoma resists immunotherapy in part because the tumor environment silences immune attack, and patients have few effective options. Identifying the podoplanin-CLEC5A-Syk signaling route as the source of that suppression points to a specific drug target, and testing Syk inhibitors alongside standard chemoradiation and checkpoint inhibitors in preclinical models could suggest a combination therapy worth taking to patients with primary or recurrent disease.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Willy Hugo
University of California-Los Angeles, CA·Microbiology & Immunology
Test whether long-term glioblastoma survivors after ATL-DC vaccination have more stem-like, progenitor-exhausted TCF7+ PD1+ CD8 T cells in their tumors, using spatial transcriptomics and high-plex immunofluorescence.
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.
David Akhavan
University of Kansas, KS·Biomedical Engineering
Develop nanocarriers, tiny drug-carrying particles, that can be loaded into CAR T cells, which are engineered tumor-targeting immune cells, to create a platform for delivering drugs into glioblastoma.
The school
Northwestern University: 71 labs on PI Pages, $1.3B a year on research, 536 research doctorates a year.
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