A5007760161- Glioma Diagnosis and Treatment
- Immune cells in cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Hippo pathway signaling and YAP/TAZ
- Cancer, Hypoxia, and Metabolism
- Neurofibromatosis and Schwannoma Cases
- Meningioma and schwannoma management
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- interferon and immune responses
- CAR-T cell therapy research
- Radiopharmaceutical Chemistry and Applications
- Melanoma and MAPK Pathways
- Cancer-related molecular mechanisms research
- Neuroblastoma Research and Treatments
- Genomics and Chromatin Dynamics
- Single-cell and spatial transcriptomics
- Cancer Mechanisms and Therapy
- Chromatin Remodeling and Cancer
- Cancer Cells and Metastasis
- MicroRNA in disease regulation
- Adenosine and Purinergic Signaling
- Virus-based gene therapy research
Fred Hutch Cancer Center
2016-2025
Huntsman Cancer Institute
2024-2025
University of Utah
2024-2025
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2023-2024
Seattle University
2023
Hospital for Sick Children
2019
SickKids Foundation
2019
University of Washington
2018
Max Delbrück Center
2012-2017
Charité - Universitätsmedizin Berlin
2013-2015
Malignant glioma belong to the most aggressive neoplasms in humans with no successful treatment available. Patients suffering from glioblastoma multiforme (GBM), highest-grade glioma, have an average survival time of only around one year after diagnosis. Both microglia and peripheral macrophages/monocytes accumulate within but fail exert effective anti-tumor activity even support tumor growth. Here we use microarray analysis compare expression profiles glioma-associated microglia/macrophages...
Gliomas harboring mutations in isocitrate dehydrogenase 1/2 (IDH1/2) have the CpG island methylator phenotype (CIMP) and significantly longer patient survival time than wild-type IDH1/2 (wtIDH1/2) tumors. Although there are many factors underlying differences between these two tumor types, immune-related cell content potentially important contributors. In order to investigate role of IDH immune response, we created a syngeneic pair mouse model for mutant IDH1 (muIDH1) wtIDH1 gliomas...
Abstract Despite a deeper molecular understanding, human glioblastoma remains one of the most treatment refractory and fatal cancers. It is known that presence macrophages microglia impact tumorigenesis prevent durable response. Herein we identify dual function cytokine IL-33 as an orchestrator microenvironment contributes to tumorigenesis. We find expression in large subset glioma specimens murine models correlates with increased tumor-associated macrophages/monocytes/microglia. In...
Genome-wide hypertranscription is common in human cancer and predicts poor prognosis. To understand how might drive cancer, we applied our formalin-fixed paraffin-embedded (FFPE)–cleavage under targeted accessible chromatin method for mapping RNA polymerase II (RNAPII) genome-wide FFPE sections. We demonstrate global RNAPII elevations mouse gliomas assorted tumors small clinical samples discover regional corresponding to de novo HER2 amplifications punctuated by likely selective sweeps....
// Xi Feng 1 , Frank Szulzewsky 2,* Alexan Yerevanian 1,3,* Zhihong Chen David Heinzmann 1,4 Rikke Darling Rasmussen Virginia Alvarez-Garcia Yeonghwan Kim 5 Bingcheng Wang 6 Ilaria Tamagno Hao Zhou 7 Xiaoxia Li Helmut Kettenmann 2 Richard M. Ransohoff 1,8 and Dolores Hambardzumyan Department of Neurosciences at Cleveland Clinic, Cleveland, Ohio, USA Cellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany 3 Case Western Reserve University School 4 Cardiology...
Glioblastomas are the most aggressive primary brain tumors in humans. Microglia/brain macrophage accumulation and around tumor correlates with malignancy poor clinical prognosis of these tumors. We have previously shown that microglia promote glioma expansion through upregulation membrane type 1 matrix metalloprotease (MT1-MMP). This depends on signaling via Toll-like receptor (TLR) adaptor molecule myeloid differentiation response gene 88 (MyD88).Using vitro, ex vivo, vivo techniques, we...
Glioblastoma (GBM) is the most aggressive malignant primary brain tumor in adults, with a median survival of 14.6 months. Recent efforts have focused on identifying clinically relevant subgroups to improve our understanding pathogenetic mechanisms and patient stratification. Concurrently, role immune cells microenvironment has received increasing attention, especially T tumor-associated macrophages (TAM). The latter are mixed population activated brain-resident microglia infiltrating...
Glioblastoma (GBM) is the most aggressive brain tumor in adults. It strongly infiltrated by microglia and peripheral monocytes that support growth. In present study we used RNA sequencing to compare expression profile of CD11b(+) human glioblastoma-associated microglia/monocytes (hGAMs) isolated from non-tumor samples. Hierarchical clustering principal component analysis showed a clear separation two sample groups identified 334 significantly regulated genes hGAMs. comparison control hGAMs...
YAP1 is a transcriptional coactivator and the principal effector of Hippo signaling pathway, which causally implicated in human cancer. Several gene fusions have been identified various cancers identifying essential components this family has significant therapeutic value. Here, we show that YAP1-MAMLD1 , YAP1-FAM118B YAP1-TFE3 YAP1-SS18 are oncogenic mice. Using reporter assays, RNA-seq, ChIP-seq, loss-of-function mutations, can all these fusion proteins exert TEAD-dependent YAP activity,...
YAP1 is a transcriptional coactivator regulated by the Hippo signaling pathway, including NF2. Meningiomas are most common primary brain tumors; large percentage exhibit heterozygous loss of chromosome 22 (harboring NF2 gene) and functional inactivation remaining copy, implicating oncogenic YAP activity in these tumors. Recently, fusions between MAML2 have been identified subset pediatric wild-type meningiomas. Here, we show that human YAP1-MAML2 -positive meningiomas resemble mutant global...
Monocytes and monocyte-derived macrophages (MDMs) from blood circulation infiltrate glioblastoma (GBM) promote growth. Here, we show that PDGFB-driven GBM cells induce the expression of potent proinflammatory cytokine IL-1β in MDM, which engages IL-1R1 tumor cells, activates NF-κB pathway, subsequently leads to induction monocyte chemoattractant proteins (MCPs). Thus, a feedforward paracrine circuit IL-1β/IL-1R1 between tumors MDM creates an interdependence driving progression. Genetic loss...
Phase separation (PS) drives the formation of biomolecular condensates that are emerging biological structures involved in diverse cellular processes. Recent studies have unveiled PS-induced several transcriptional factor (TF) transcriptionally active, but how strongly PS promotes gene activation remains unclear. Here, we show oncogenic TF fusion Yes-associated protein 1-Mastermind like coactivator 2 (YAP-MAML2) undergoes and forms liquid-like bear hallmarks activity. Furthermore, examined...
GPR34 is a G i/o protein‐coupled receptor (GPCR) of the nucleotide P2Y 12 ‐like group. This highly expressed in microglia, however, functional relevance these glial cells unknown. Previous results suggested an impaired immune response GPR34‐deficient mice infected with Cryptococcus neoformans . Here we show that deficiency morphological changes retinal and cortical microglia. RNA sequencing analysis microglia revealed number differentially transcripts involved cell motility phagocytosis. We...
Poststroke angiogenesis contributes to long-term recovery after stroke. Signal transducer and activator of transcription-3 (Stat3) is a key regulator for various inflammatory signals angiogenesis. It was the aim this study determine its function in poststroke outcome.We generated tamoxifen-inducible endothelial-specific Stat3 knockout mouse model by crossbreeding Stat3(floxed/KO) Tie2-Cre(ERT2) mice. Cerebral ischemia induced 30 minutes middle cerebral artery occlusion. We demonstrated that...
Abstract Paediatric high-grade gliomas (HGGs) account for the most brain tumour-related deaths in children and have a median survival of 12–15 months. One promising avenue research is development novel therapies targeting properties non-neoplastic cell-types within tumour such as associated macrophages (TAMs). TAMs are immunosuppressive promote malignancy adult HGG; however, paediatric medulloblastoma, exhibit anti-tumour properties. Much known about HGG, yet little them setting. This raises...
Dexamethasone is used to manage cerebral oedema in patients with glioblastoma, despite significant drawbacks. Herting et al. show that dexamethasone reduces via inhibition of interleukin-1 signalling. They highlight a likely interaction between and immunotherapy, propose specific may be preferable for managing oedema.
Meningiomas, although mostly benign, can be recurrent and fatal. World Health Organization (WHO) grading of the tumor does not always identify high-risk meningioma, better characterizations their aggressive biology are needed. To approach this problem, we combined 13 bulk RNA sequencing (RNA-seq) datasets to create a dimension-reduced reference landscape 1,298 meningiomas. The clinical genomic metadata effectively correlated with regions, which led identification meningioma subtypes specific...
Recently, neurotransmitters/neurohormones have been identified as factors controlling the function of microglia, immune competent cells central nervous system. In this study, we compared responsiveness microglia to neurotransmitters/neurohormones. We freshly isolated from healthy adult C57Bl/6 mice and found that only a small fraction (1–20%) responded application endothelin, histamine, substance P, serotonin, galanin, somatostatin, angiotensin II, vasopressin, neurotensin, dopamine, or...
Abstract High‐grade gliomas (HGG), including glioblastomas, are characterized by invasive growth, resistance to therapy, and high inter‐ intra‐tumoral heterogeneity. The key histological hallmarks of glioblastoma pseudopalisading necrosis microvascular proliferation, which allow pathologists distinguish from lower‐grade gliomas. In addition being genetically molecularly heterogeneous, HGG also heterogeneous with respect the composition their microenvironment. question whether this...
Glioblastoma is the most frequently occurring and invariably fatal primary brain tumor in adults. The vast majority of glioblastomas characterized by chromosomal copy number alterations, including gain whole chromosome 7 loss 10. Gain an early event gliomagenesis that occurs proneural-like precursor cells, which give rise to all isocitrate dehydrogenase (IDH) wild-type glioblastoma transcriptional subtypes. Platelet-derived growth factor A ( PDGFA ) one gene on known drive gliomagenesis,...