Eric W. Prince

Pericyte KATP channel hyperactivity redistributes cortical blood flow in a CADASIL mouse model

Danielle A Jeffrey, Eric W. Prince, Niloufar Khakpour, Hannah R Ferris et autres

Abstract Cerebral hemodynamic dysfunction is a key driver of unhealthy brain aging. Impaired microcirculatory reactivity leads to uneven perfusion, rendering deeper brain regions more vulnerable and thereby contributing to cognitive decline. Yet how capillaries contribute to these deficits remains poorly defined. Here …

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Abstract B009: Cancer-associated fibroblasts remodel the extracellular matrix in Adamantinomatous Craniopharyngioma

Timothy H Chang, Shanthi Rangaswamy, John Jeang, Scott Haston et autres

Abstract Adamantinomatous craniopharyngiomas (ACPs) are benign but locally invasive pituitary tumors that cause significant neuroendocrine morbidity due to their proximity to critical brain structures. Standard of care is surgical resection and radiation, with no effective medical therapies available. Despite intervention, up to …

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Differential phagocytosis induces diverse macrophage activation states in malignant gliomas

Senthilnath Lakshmanachetty, Kent Riemondy, Bridget L. Sanford, Andrew M. Donson et autres

BACKGROUND: Diffuse midline glioma (DMG) and glioblastoma (GBM) are aggressive brain tumors with limited treatment options. Macrophage phagocytosis is a complex, tightly regulated process governed by competing pro-phagocytic and anti-phagocytic signals. CD47-SIRPα signaling inhibits macrophage activity, while radiotherapy (RT) can enhance tumor …

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Figure S2 from SIRT2 Regulates the SMARCB1 Loss-Driven Differentiation Block in ATRT

Irina N. Alimova, Dong Wang, John A. DeSisto, Etienne P. Danis et autres

SIRT2 is essential for ATRT growth. A. Genetic knockdown SIRT2 decreases SIRT2 mRNA in BT16(MYC) and MAF737(TYR) cells as measured by RT qPCR assay ( **p<0.01). B. Western Blot of SIRT2 demonstrates shRNA mediated knockdown in BT16(MYC) and MAF737(TYR) cells. C. Membranes …

Figure S5 from SIRT2 Regulates the SMARCB1 Loss-Driven Differentiation Block in ATRT

Irina N. Alimova, Dong Wang, John A. DeSisto, Etienne P. Danis et autres

Tenovin6 and TM treatment effect on different groups ATRT cells and Normal Human Astrocytes. A. Representative images of Colony formation assay following Tenovin6 treatment of BT16(MYC) and MAF737(TYR) . B. Quantification of Colony formation assay. Tenovin6 significantly inhibits clonogenic potential of BT16(MYC) …

Figure S4 from SIRT2 Regulates the SMARCB1 Loss-Driven Differentiation Block in ATRT

Irina N. Alimova, Dong Wang, John A. DeSisto, Etienne P. Danis et autres

Immunohistochemistry images and quantifications. A, B. In vivo analysis of SIRT2 depletion on MAF737(TYR) and BT16(MYC) ATRT tumors show decreased Ki67 and SIRT2 stains accumulation (40x magnification). On the right, plots show values from quantification representative images. Stain accumulation from 5 fields …

Figure S10 from SIRT2 Regulates the SMARCB1 Loss-Driven Differentiation Block in ATRT

Irina N. Alimova, Dong Wang, John A. DeSisto, Etienne P. Danis et autres

A, B. ELDA assay. Neurosphere size following TM treatment (20uM and 25uM respectively) of BT16(MYC) cells and CHB-ATRT1(MYC) for 50, 25,10 and 1 cell seeded per well.

Figure S7 from SIRT2 Regulates the SMARCB1 Loss-Driven Differentiation Block in ATRT

Irina N. Alimova, Dong Wang, John A. DeSisto, Etienne P. Danis et autres

SIRT2 inhibition leads to apoptosis in ATRT cells. ATRT cell lines were treated with their respective IC50 of Tenovin6 or TM for 72h and apoptosis was measured using Annexin V FITC reagent. Bar chart showing increased proportion of apoptotic cells after treatment. …

Data from SIRT2 Regulates the SMARCB1 Loss-Driven Differentiation Block in ATRT

Irina N. Alimova, Dong Wang, John A. DeSisto, Etienne P. Danis et autres

Abstract An atypical teratoid rhabdoid tumor (ATRT) is a highly aggressive pediatric brain tumor driven by the loss of SMARCB1, which results in epigenetic dysregulation of the genome. SMARCB1 loss affects lineage commitment and differentiation by controlling gene expression. We hypothesized that …

Figure S8 from SIRT2 Regulates the SMARCB1 Loss-Driven Differentiation Block in ATRT

Irina N. Alimova, Dong Wang, John A. DeSisto, Etienne P. Danis et autres

A. Metascape gene ontology network cluster constructed from common genes up- or downregulated by Tenovin6 treatment. Each node denotes an enriched term, and networked clusters are indicated by different colors (Figure was created by http://metascape.org). B,C. Illustrative genes with fold-change 1 and …

Figure S1 from SIRT2 Regulates the SMARCB1 Loss-Driven Differentiation Block in ATRT

Irina N. Alimova, Dong Wang, John A. DeSisto, Etienne P. Danis et autres

Colony Formation Assay and SIRT2 expression in ATRT subgroups. A. CFA for hits genes in MAF737 ATRT from shRNA screen. Representative images of colony formations. B. Quantification of CFA. SIRT2 depletion results in a significant loss of ATRT cell viability (*p <0.001). …

Figure S11 from SIRT2 Regulates the SMARCB1 Loss-Driven Differentiation Block in ATRT

Irina N. Alimova, Dong Wang, John A. DeSisto, Etienne P. Danis et autres

SIRT2 inhibition suppressed BT16(MYC) ATRT growth in vivo. A. Bioluminescence images of orthotopic ATRT tumors treated with Vehicle (Control) or TM. B. Survival analysis of Vehicle vs TM treated animals (median 19 days vs 33 days, log rank test p<0.05, n=4). C. …