Frank Szulzewsky
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View article: C-terminal fusion partner activity contributes to the oncogenic functions of YAP1::TFE3
C-terminal fusion partner activity contributes to the oncogenic functions of YAP1::TFE3 Open
View article: Development of PROTACs for targeted degradation of oncogenic TRK fusions
Development of PROTACs for targeted degradation of oncogenic TRK fusions Open
Chromosomal translocations leading to the fusion of tropomyosin receptor kinases (TRK) with diverse partner proteins have been identified as oncogenic drivers in many adult and pediatric cancers. While first-generation TRK kinase inhibitor…
View article: C-terminal fusion partner activity contributes to the oncogenic functions of YAP1::TFE3
C-terminal fusion partner activity contributes to the oncogenic functions of YAP1::TFE3 Open
YAP1 gene fusions are found in a multitude of human tumors, are potent oncogenic drivers, and are the likely initiating tumorigenic events in these tumors. We and others have previously shown that a YAP1 fusion proteins exert TEAD-dependen…
View article: RNA polymerase II at histone genes predicts outcome in human cancer
RNA polymerase II at histone genes predicts outcome in human cancer Open
Genome-wide hypertranscription is common in human cancer and predicts poor prognosis. To understand how hypertranscription might drive cancer, we applied our formalin-fixed paraffin-embedded (FFPE)–cleavage under targeted accessible chroma…
View article: ERK signaling promotes resistance to TRK kinase inhibition in NTRK fusion-driven glioma mouse models
ERK signaling promotes resistance to TRK kinase inhibition in NTRK fusion-driven glioma mouse models Open
View article: <scp>TRKing</scp> down drug resistance in <scp>NTRK</scp> fusion‐positive cancers<sup>†</sup>
<span>TRKing</span> down drug resistance in <span>NTRK</span> fusion‐positive cancers<sup>†</sup> Open
In a recent issue of The Journal of Pathology , Chen and colleagues established novel patient‐derived ex vivo models of NTRK fusion‐positive soft tissue sarcoma to characterize resistance mechanisms against targeted therapy with tyrosine k…
View article: Aggressive high-grade NF2 mutant meningiomas downregulate oncogenic YAP signaling via the upregulation of VGLL4 and FAT3/4
Aggressive high-grade NF2 mutant meningiomas downregulate oncogenic YAP signaling via the upregulation of VGLL4 and FAT3/4 Open
Meningiomas are the most common primary brain tumors in adults. Although generally benign, a subset of meningiomas is of higher grade, shows aggressive growth behavior and recurs even after multiple surgeries. Around half of all meningioma…
View article: Meningioma transcriptomic landscape demonstrates novel subtypes with regional associated biology and patient outcome
Meningioma transcriptomic landscape demonstrates novel subtypes with regional associated biology and patient outcome Open
Meningiomas, although mostly benign, can be recurrent and fatal. World Health Organization (WHO) grading of the tumor does not always identify high-risk meningioma, and better characterizations of their aggressive biology are needed. To ap…
View article: Meningioma: current updates on genetics, classification, and mouse modeling
Meningioma: current updates on genetics, classification, and mouse modeling Open
Meningiomas, the most common primary brain tumors in adults, are often benign and curable by surgical resection. However, a subset is of higher grade, shows aggressive growth behavior as well as brain invasion, and often recurs even after …
View article: ERK signaling promotes resistance to TRK kinase inhibition in NTRK fusion-driven glioma mouse models
ERK signaling promotes resistance to TRK kinase inhibition in NTRK fusion-driven glioma mouse models Open
Pediatric-type high-grade gliomas frequently harbor gene fusions involving receptor tyrosine kinase genes, including neurotrophic tyrosine kinase receptor (NTRK) fusions. Clinically, these tumors show high initial response rates to tyrosin…
View article: RNA Polymerase II hypertranscription at histone genes in cancer FFPE samples
RNA Polymerase II hypertranscription at histone genes in cancer FFPE samples Open
Genome-wide hypertranscription is common in hu-man cancer and predicts poor prognosis. To under-stand how hypertranscription might drive cancer, we applied our FFPE-CUTAC method for mapping RNA Polymerase II (RNAPII) genome-wide in formali…
View article: Haploinsufficiency of phosphodiesterase 10A activates PI3K/AKT signaling independent of PTEN to induce an aggressive glioma phenotype
Haploinsufficiency of phosphodiesterase 10A activates PI3K/AKT signaling independent of PTEN to induce an aggressive glioma phenotype Open
Glioblastoma is universally fatal and characterized by frequent chromosomal copy number alterations harboring oncogenes and tumor suppressors. In this study, we analyzed exome-wide human glioblastoma copy number data and found that cytoban…
View article: Meningioma transcriptomic landscape demonstrates novel subtypes with regional associated biology and patient outcome
Meningioma transcriptomic landscape demonstrates novel subtypes with regional associated biology and patient outcome Open
Summary Meningiomas, the most common intracranial tumor, though mostly benign can be recurrent and fatal. WHO grading does not always identify high risk meningioma and better characterizations of their aggressive biology is needed. To appr…
View article: Phase separation of YAP-MAML2 differentially regulates the transcriptome
Phase separation of YAP-MAML2 differentially regulates the transcriptome Open
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 formation of several transcriptional factor (TF)…
View article: Meningioma Transcriptomic Landscape Demonstrates Novel Subtypes with Regional Associated Biology and Patient Outcome
Meningioma Transcriptomic Landscape Demonstrates Novel Subtypes with Regional Associated Biology and Patient Outcome Open
View article: Aggressive high-grade NF2 mutant meningiomas downregulate oncogenic YAP signaling via the upregulation of VGLL4 and FAT3/4
Aggressive high-grade NF2 mutant meningiomas downregulate oncogenic YAP signaling via the upregulation of VGLL4 and FAT3/4 Open
Background Meningiomas are the most common primary central nervous system tumors in adults. Although generally benign, a subset is of higher grade and ultimately fatal. Around half of all meningiomas harbor inactivating mutations in NF2, l…
View article: PATH-49. COMPREHENSIVE RNA-SEQ ANALYSIS REVEALS NOVEL SUBTYPES OF MENINGIOMAS AND PREDICTS PATIENT OUTCOME.
PATH-49. COMPREHENSIVE RNA-SEQ ANALYSIS REVEALS NOVEL SUBTYPES OF MENINGIOMAS AND PREDICTS PATIENT OUTCOME. Open
OBJECTIVE Meningiomas are the most common intracranial tumor in humans. While most tumors are benign, some are malignant and ultimately lethal. Current grading systems based on WHO grade do not provide adequate risk stratification, therefo…
View article: MODL-41. LOSS OF DISTAL CHROMOSOME 6Q AND ASSOCIATED <i>PDE10A</i> INDUCES AN AGGRESSIVE GLIOMA PHENOTYPE BY FACILITATING PRONEURAL TO MESENCHYMAL TRANSITION
MODL-41. LOSS OF DISTAL CHROMOSOME 6Q AND ASSOCIATED <i>PDE10A</i> INDUCES AN AGGRESSIVE GLIOMA PHENOTYPE BY FACILITATING PRONEURAL TO MESENCHYMAL TRANSITION Open
Somatic copy number alterations (SCNAs) are common in glioblastoma, with some SCNAs having prognostic implications. Identifying and characterizing SCNA-related genes acting as oncogenes or tumor suppressors may potentially provide new ther…
View article: MODL-31. USING GENETICALLY-ENGINEERED MOUSE MODELS OF TREATMENT-NAÏVE AND -EXPERIENCED NTRK FUSION-DRIVEN GLIOMAS FOR PRE-CLINICAL TRIALS OF TYROSINE KINASE INHIBITORS
MODL-31. USING GENETICALLY-ENGINEERED MOUSE MODELS OF TREATMENT-NAÏVE AND -EXPERIENCED NTRK FUSION-DRIVEN GLIOMAS FOR PRE-CLINICAL TRIALS OF TYROSINE KINASE INHIBITORS Open
Gene fusions that contain the kinase domain of the three neurotrophic tyrosine kinase receptor (NTRK) genes are frequently observed in infantile high and low-grade gliomas. While these tumors initially respond to treatment with NTRK tyrosi…
View article: Epigenomic analysis of formalin-fixed paraffin-embedded samples by CUT&Tag
Epigenomic analysis of formalin-fixed paraffin-embedded samples by CUT&Tag Open
View article: A paracrine circuit of IL-1β/IL-1R1 between myeloid and tumor cells drives genotype-dependent glioblastoma progression
A paracrine circuit of IL-1β/IL-1R1 between myeloid and tumor cells drives genotype-dependent glioblastoma progression Open
Monocytes and monocyte-derived macrophages (MDMs) from blood circulation infiltrate glioblastoma (GBM) and promote growth. Here, we show that PDGFB-driven GBM cells induce the expression of the potent proinflammatory cytokine IL-1β in MDM,…
View article: Epigenomic analysis of Formalin-Fixed Paraffin-Embedded samples by CUT&Tag
Epigenomic analysis of Formalin-Fixed Paraffin-Embedded samples by CUT&Tag Open
For more than a century, Formalin Fixed Paraffin Embedded (FFPE) sample preparation has been the preferred method for long-term preservation of biological material. However, the use of FFPE samples for epigenomic studies has been difficult…
View article: Visualizing genomic characteristics across an RNA-Seq based reference landscape of normal and neoplastic brain
Visualizing genomic characteristics across an RNA-Seq based reference landscape of normal and neoplastic brain Open
In order to better understand the relationship between normal and neoplastic brain, we combined five publicly available large-scale datasets, correcting for batch effects and applying Uniform Manifold Approximation and Projection (UMAP) to…
View article: An RNA seq-based reference landscape of human normal and neoplastic brain
An RNA seq-based reference landscape of human normal and neoplastic brain Open
In order to better understand the relationship between normal and neoplastic brain, we combined five publicly available large-scale datasets, correcting for batch effects and applying Uniform Manifold Approximation and Projection (UMAP) to…
View article: An RNA seq-based reference landscape of human normal and neoplastic brain
An RNA seq-based reference landscape of human normal and neoplastic brain Open
In order to better understand the relationship between normal and neoplastic brain, we combined five publicly available large-scale datasets, correcting for batch effects and applying Uniform Manifold Approximation and Projection (UMAP) to…
View article: MODL-36. EXPRESSION OF YAP1-MAML2 AND CONSTITUTIVELY ACTIVE YAP1 DRIVE THE FORMATION OF MENINGIOMA-LIKE TUMORS IN MICE THAT RESEMBLE NF2-MUTANT MENINGIOMAS
MODL-36. EXPRESSION OF YAP1-MAML2 AND CONSTITUTIVELY ACTIVE YAP1 DRIVE THE FORMATION OF MENINGIOMA-LIKE TUMORS IN MICE THAT RESEMBLE NF2-MUTANT MENINGIOMAS Open
YAP1 is a transcriptional co-activator and oncogene under the control of the Hippo Signaling Pathway. Functional inactivation of Hippo Pathway tumor suppressors, including NF2, are frequent events in human cancers. Meningiomas are the most…
View article: Oncogenic role of a developmentally regulated <i>NTRK2</i> splice variant
Oncogenic role of a developmentally regulated <i>NTRK2</i> splice variant Open
Temporally regulated alternative splicing choices are vital for proper development, yet the wrong splice choice may be detrimental. Here, we highlight a previously unidentified role for the neurotrophin receptor splice variant TrkB.T1 in n…
View article: Both YAP1-MAML2 and constitutively active YAP1 drive the formation of tumors that resemble NF2 mutant meningiomas in mice
Both YAP1-MAML2 and constitutively active YAP1 drive the formation of tumors that resemble NF2 mutant meningiomas in mice Open
YAP1 is a transcriptional coactivator regulated by the Hippo signaling pathway, including NF2. Meningiomas are the most common primary brain tumors; a large percentage exhibit heterozygous loss of chromosome 22 (harboring the NF2 gene) and…
View article: Oncogenic role of a developmentally regulated NTRK2 splice variant
Oncogenic role of a developmentally regulated NTRK2 splice variant Open
Temporally-regulated alternative splicing choices are vital for proper development yet the wrong splice choice may be detrimental. Here we highlight a novel role for the neurotrophin receptor splice variant TrkB.T1 in neurodevelopment, emb…
View article: Oncogenic role of a developmentally regulated NTRK2 splice variant
Oncogenic role of a developmentally regulated NTRK2 splice variant Open
Temporally-regulated alternative splicing choices are vital for proper development yet the wrong splice choice may be detrimental. Here we highlight a novel role for the neurotrophin receptor splice variant TrkB.T1 in neurodevelopment, emb…