transcriptomic analysis

Sparks, flames, and inferno: epileptogenesis in the glioblastoma microenvironment

Glioblastoma cells trigger pharmacoresistant seizures that may promote tumor growth and diminish the quality of remaining life. To define the relationship between growth of glial tumors and their neuronal microenvironment, and to identify genomic biomarkers and mechanisms that may point to better prognosis and treatment of drug resistant epilepsy in brain cancer, we are analyzing a new generation of genetically defined CRISPR/in utero electroporation inborn glioblastoma (GBM) tumor models engineered in mice. The molecular pathophysiology of glioblastoma cells and surrounding neurons and untransformed astrocytes are compared at serial stages of tumor development. Initial studies reveal that epileptiform EEG spiking is a very early and reliable preclinical signature of GBM expansion in these mice, followed by rapidly progressive seizures and death within weeks. FACS-sorted transcriptomic analysis of cortical astrocytes reveals the expansion of a subgroup enriched in pro-synaptogenic genes that may drive hyperexcitability, a novel mechanism of epileptogenesis. Using a prototypical GBM IUE model, we systematically define and correlate the earliest appearance of cortical hyperexcitability with progressive cortical tumor cell invasion, including spontaneous episodes of spreading cortical depolarization, innate inflammation, and xCT upregulation in the peritumoral microenvironment. Blocking this glutamate exporter reduces seizure load. We show that the host genome contributes to seizure risk by generating tumors in a monogenic deletion strain (MapT/tau -/-) that raises cortical seizure threshold. We also show that the tumor variant profile determines epilepsy risk. Our genetic dissection approach sets the stage to broadly explore the developmental biology of personalized tumor/host interactions in mice engineered with novel human tumor mutations in specified glial cell lineages.

Visual impairments in a mouse model of multiple sclerosis: A transcriptomic analysis

FENS Forum 2024

Functional and transcriptomic analysis of induced pluripotent stem cell microglia in Huntington’s Disease

Spot-on! Spatial transcriptomic analysis of L-DOPA-induced gene expression in a mouse model of parkinsonism

Transcriptomic analysis’ of axon regeneration-inducing manipulations discover distinct molecular programs defining a cell’s fate to die, survive or regenerate after an injury

Transcriptomic analysis of cytoplasmic polyadenylation element binding proteins (CPEBs) in Schizophrenia

Transcriptomic analysis of hippocampal subregions after induction of acute seizures by electric stimulation of the perforant pathway in rats

Proteomic and transcriptomic analysis of Id2- and Ascl4-induced wiring in adult hippocampal granule cells

FENS Forum 2024

Transcriptomic analysis of the effects of a single dose of ibogaine: Uncovering potential therapeutic pathways in mice

FENS Forum 2024