Dolores Hambardzumyan
University of Pennsylvania, PA·Microbiology & Immunology
Glioblastoma, the most lethal brain cancer in adults, and high-grade gliomas in children are fatal tumors with few treatment options. Much of a brain tumor is not cancer cells at all.
- Fields
Microbiology & Immunology
Neuroscience
Medicine & Clinical Research
- Topics
glioblastoma
pediatric high-grade glioma
pHGG
- Grants
- 3 known grants, through Mar 2029
What they work on
- 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.
- Test how TNFα signaling and other neutrophil-derived signals drive neutrophil-tumor crosstalk and growth, with or without monocytes, and measure the immune-suppressing activity of each myeloid subset.
- Test whether blocking both monocyte and neutrophil entry from the blood slows glioblastoma growth and activates T cells, including with two small-molecule inhibitors.
- Determine how pediatric histone mutations, PDGFA versus PDGFB drivers, and hemisphere versus brainstem location shape myeloid infiltration in newborn immunocompetent mouse models of pediatric high-grade glioma.
- Test whether CCL3-driven monocyte recruitment and CXCL1-driven neutrophil recruitment promote pediatric glioma growth, and whether blocking them is a viable therapy.
- Determine how IL-1β from blood-derived monocytes and macrophages makes vessels leaky and causes edema, using cell type-specific IL-1β deletion in three mouse glioblastoma models and patient-derived xenografts.
- Test whether blocking IL-1β reduces brain swelling and tumor growth without weakening radiotherapy, as an alternative to dexamethasone and anti-VEGF drugs.
More about the research
Up to a third can be myeloid cells, immune cells such as macrophages and neutrophils that are recruited from the blood or already live in the brain. These cells often help the tumor grow, suppress the attack by other immune cells, and cause dangerous brain swelling. Yet drugs targeting them have largely failed. This work asks which myeloid cells enter brain tumors, why they come, and how blocking them could slow tumors and ease side effects. It uses genetically engineered mice that carry human tumor-driving mutations and have intact immune systems, together with patient samples.
Why it matters
Patients with glioblastoma and children with high-grade gliomas face grim survival and few options. This work could explain why myeloid-targeted drugs have failed and point to combined blockade of monocyte and neutrophil entry as a treatment strategy. It could also offer IL-1β targeting as a way to control brain swelling without the side effects of dexamethasone or anti-VEGF drugs, which may help radiation and immunotherapy work better.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Tohru Yamada
University of Illinois Chicago, IL·Pharmacology
Determine the pharmacological activity of AmiR20-p28, an antisense RNA against the cancer-promoting microRNA miR20a joined to the cell-penetrating peptide p28, in cell and mouse models of pediatric glioblastoma and diffuse intrinsic pontine glioma.
Stefanie Galban
University of Michigan, MI·Medicine & Clinical Research
Determine how ALDH1A3 and ALDH2, enzymes marking cancer stem cells, are controlled by the H3 K27M histone mutation and by IL1β from microglia, using isogenic DIPG models in vitro and in vivo.
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.
The school
University of Pennsylvania: 90 labs on PI Pages, $2.2B a year on research, 750 research doctorates a year.
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