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Julian Taranda

Other affiliations: Cold Spring Harbor Laboratory
Bio: Julian Taranda is an academic researcher from University Hospital Heidelberg. The author has contributed to research in topics: Receptor tyrosine kinase & Chromosome 7 (human). The author has an hindex of 1, co-authored 5 publications receiving 4 citations. Previous affiliations of Julian Taranda include Cold Spring Harbor Laboratory.

Papers
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Journal ArticleDOI
15 Apr 2021-Cancers
TL;DR: In this paper, the authors summarize the preclinical utility of in vivo imaging using two-photon microscopy in brain tumors and present ex vivo approaches (light-sheet fluorescence microscopy and serial twophoton tomography) and highlight their current and potential utility in neuro-oncology using data from solid tumors or pathological brain.
Abstract: Although our understanding of the two-dimensional state of brain tumors has greatly expanded, relatively little is known about their spatial structures. The interactions between tumor cells and the tumor microenvironment (TME) occur in a three-dimensional (3D) space. This volumetric distribution is important for elucidating tumor biology and predicting and monitoring response to therapy. While static 2D imaging modalities have been critical to our understanding of these tumors, studies using 3D imaging modalities are needed to understand how malignant cells co-opt the host brain. Here we summarize the preclinical utility of in vivo imaging using two-photon microscopy in brain tumors and present ex vivo approaches (light-sheet fluorescence microscopy and serial two-photon tomography) and highlight their current and potential utility in neuro-oncology using data from solid tumors or pathological brain as examples.

5 citations

Posted ContentDOI
24 Aug 2021-bioRxiv
TL;DR: In this paper, the mesenchyme homeobox 2 (MEOX2) was identified as an oncogene in human glioblastoma (GBM).
Abstract: Glioblastoma (GBM) is an aggressive tumor that frequently exhibits gain of chromosome 7, loss of chromosome 10 and aberrantly activated receptor tyrosine kinase signaling pathways. Here, we identify mesenchyme homeobox 2 (MEOX2) on chromosome 7 with increased expression in GBM as a salient oncogenic transcription factor. Specifically, we show that MEOX2 overexpression leads to increased ERK phosphorylation, and we identify a phosphorylation site on MEOX2 that regulates its transcriptional activity by altering its subnuclear localization. We show that MEOX2 overexpression can lead to increased growth in GBM implantation models and cooperates with loss of p53 and PTEN in cerebral organoid models of human malignant gliomas to induce cell proliferation. Furthermore, using high-throughput genomics, we identify transcriptional target genes of MEOX2 in patient-derived GBM tumorsphere models and a fresh frozen GBM tumor. These analyses show that MEOX2 activates several oncogenic pathways involved in MAPK signaling and extracellular matrix organization. Furthermore, MEOX2 binds to oncogenic ETS factors and known glioma oncogenes such as FABP7. In total, we reveal a novel role for MEOX2 in GBM initiation and progression and demonstrate that MEOX2 can enhance ERK signaling through a feed-forward mechanism. Significance StatementGlioblastoma (GBM) harbors gain of chromosome 7 as an early driver event. In this study, we show that mesenchyme homeobox 2 (MEOX2), an aberrantly upregulated transcription factor on chromosome 7, is an oncogene in human glioblastoma. In contrast to GBM, MEOX2 expression is very low in normal brain. We show that MEOX2 cooperates with p53 and PTEN loss to promote tumor initiation in cerebral organoid models. In addition, we identify direct and indirect molecular targets of MEOX2 and demonstrate its role in activating the ERK signaling cascade. These findings identify a novel oncogene in GBM and highlight the transcriptional networks hijacked by these tumors to activate signaling pathways central to GBM biology.

3 citations

Book ChapterDOI
01 Jan 2021
TL;DR: In this paper, the authors highlight recent advances in solid tumor epigenetics, specifically focusing on epigenetic therapies and the most promising combination strategies currently under investigation, and illustrate the utility of epigenetic markers for solid tumor classification.
Abstract: The majority of solid tumors harbor disrupted epigenomes that contribute to malignancy. Over the past decade, there has been a substantial increase in our understanding of the epigenetic mechanisms underlying normal and disease states. Profiling of tumors revealed recurrent mutations in key components of the epigenetic machinery and metabolic enzymes that lead to an altered epigenetic state and oncogenic transformation. Unlike genetic events, epigenetic alterations can be targeted pharmacologically and potentially reversed. Drug discovery efforts are focused on developing epigenetic drugs and treatment regimens. Recently, altered DNA methylation has emerged as an important and promising feature for tumor classification. In this chapter, we highlight recent advances in solid tumor epigenetics, specifically focusing on epigenetic therapies and the most promising combination strategies currently under investigation. In addition, we illustrate the utility of epigenetic markers for solid tumor classification and the emerging field of analyzing epigenetic biomarkers in liquid biopsies.

3 citations

Journal ArticleDOI
TL;DR: In this paper, the authors describe an approach to study the processes of initiation, progression, and metastasis of prostate cancer (PC) in a genetically engineered RapidCaP mouse model, which combines whole-organ imaging by serial two-photon tomography (STPT) and post hoc thick-section immunofluorescent (IF) analysis.

1 citations

Posted ContentDOI
08 Nov 2021-bioRxiv
TL;DR: Tripartite Motif Containing 67 (TRIM67) as mentioned in this paper is an E3 ubiquitin ligase with essential roles during neuronal development, which is an oncogene distinctly upregulated in oligodendrogliomas.
Abstract: Oligodendrogliomas are a subtype of isocitrate dehydrogenase (IDH) mutant gliomas defined by the co-deletion of chromosome arms 1p and 19q. Although the somatic genomic alterations of oligodendrogliomas have been well described, transcriptional changes unique to these tumors are not well studied. Here, we identify Tripartite Motif Containing 67 (TRIM67), an E3 ubiquitin ligase with essential roles during neuronal development, as an oncogene distinctly upregulated in oligodendrogliomas. We characterize the function of TRIM67 using high throughput assays, including RNA sequencing, total lysate-mass spectrometry (MS) and co-immunoprecipitation (IP)-MS using human neural progenitor cells and patient-derived glioma tumorspheres constitutively overexpressing TRIM67. Our high throughput data suggest that TRIM67 overexpression alters the abundance of cytoskeletal proteins, which were validated by functional assays, including immunofluorescence (IF) staining, co-IP and western blotting (WB). Additionally, IF staining results indicate that TRIM67 ectopic expression induces formation of membrane blebs in glioma cells, which could be reverted with the nonmuscle class II myosin inhibitor blebbistatin and selective ROCK inhibitor fasudil. GTP pulldown and WB assays further indicate that Rho GTPase/ROCK2 signaling is altered upon TRIM67 ectopic expression. Phenotypically, TRIM67 expression resulted in higher cell motility in wound healing experiments, reduced cell adherence in adhesion assays, accelerated tumor growth and reduced survival in mouse orthotopic implantation models of an oligodendroglioma-derived patient tumorsphere line. Taken together, our results demonstrate that upregulated TRIM67 induces blebbing-based rounded cell morphology through Rho GTPase/ROCK-mediated signaling thereby contributing to glioma pathogenesis.

Cited by
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01 Nov 2013
TL;DR: In this article, a review of the interactions between EMT-inducing transcription factors and epigenetic modulators during cancer progression and the therapeutic implications of exploiting this intricate regulatory process is presented.
Abstract: Epithelial-mesenchymal transitions (EMTs) are a key requirement for cancer cells to metastasize and colonize in a new environment. Epithelial-mesenchymal plasticity is mediated by master transcription factors and is also subject to complex epigenetic regulation. This Review outlines our current understanding of the interactions between EMT-inducing transcription factors and epigenetic modulators during cancer progression and the therapeutic implications of exploiting this intricate regulatory process. During the course of malignant cancer progression, neoplastic cells undergo dynamic and reversible transitions between multiple phenotypic states, the extremes of which are defined by the expression of epithelial and mesenchymal phenotypes. This plasticity is enabled by underlying shifts in epigenetic regulation. A small cohort of pleiotropically acting transcription factors is widely recognized to effect these shifts by controlling the expression of a constituency of key target genes. These master regulators depend on complex epigenetic regulatory mechanisms, notably the induction of changes in the modifications of chromatin-associated histones, in order to achieve the widespread changes in gene expression observed during epithelial-mesenchymal transitions (EMTs). These associations indicate that an understanding of the functional interactions between such EMT-inducing transcription factors and the modulators of chromatin configuration will provide crucial insights into the fundamental mechanisms underlying cancer progression and may, in the longer term, generate new diagnostic and therapeutic modalities for treating high-grade malignancies.

797 citations

01 Jan 2017
TL;DR: In this article, the synergy of BET bromodomain inhibition with PARP inhibition in BRCA-proficient ovarian cancers due to mitotic catastrophe was shown. And the combination of PARP inhibitor Olaparib and the BET inhibitor JQ1 showed a synergistic increase in DNA damage and checkpoint defects, which allowed cells to enter mitosis despite the accumulation of DNA damage.
Abstract: PARP inhibition is known to be an effective clinical strategy in BRCA mutant cancers, but PARP inhibition has not been applied to BRCA-proficient tumors. Here, we show the synergy of BET bromodomain inhibition with PARP inhibition in BRCA-proficient ovarian cancers due to mitotic catastrophe. Treatment of BRCA-proficient ovarian cancer cells with the BET inhibitor JQ1 downregulated the G2-M cell-cycle checkpoint regulator WEE1 and the DNA-damage response factor TOPBP1. Combining PARP inhibitor Olaparib with the BET inhibitor, we observed a synergistic increase in DNA damage and checkpoint defects, which allowed cells to enter mitosis despite the accumulation of DNA damage, ultimately causing mitotic catastrophe. Moreover, JQ1 and Olaparib showed synergistic suppression of growth of BRCA-proficient cancer in vivo in a xenograft ovarian cancer mouse model. Our findings indicate that a combination of BET inhibitor and PARP inhibitor represents a potential therapeutic strategy for BRCA-proficient cancers.

65 citations

01 Nov 2016
TL;DR: Evidence is reviewed that insulated neighborhoods provide for specific enhancer-gene interactions, are essential for both normal gene activation and repression, form a chromosome scaffold that is largely preserved throughout development, and are perturbed by genetic and epigenetic factors in disease.
Abstract: Understanding how transcriptional enhancers control over 20,000 protein-coding genes to maintain cell-type-specific gene expression programs in all human cells is a fundamental challenge in regulatory biology. Recent studies suggest that gene regulatory elements and their target genes generally occur within insulated neighborhoods, which are chromosomal loop structures formed by the interaction of two DNA sites bound by the CTCF protein and occupied by the cohesin complex. Here, we review evidence that insulated neighborhoods provide for specific enhancer-gene interactions, are essential for both normal gene activation and repression, form a chromosome scaffold that is largely preserved throughout development, and are perturbed by genetic and epigenetic factors in disease. Insulated neighborhoods are a powerful paradigm for gene control that provides new insights into development and disease.

16 citations

Journal ArticleDOI
TL;DR: In this paper , a GAN-LSTM-3D method is proposed for 3D reconstruction of lung cancer tumours from 2D CT images, which consists of three phases: lung segmentation, tumour segmentation and tumour reconstruction.

3 citations

Journal ArticleDOI
TL;DR: In this article , a hybrid texture-based feature extraction (HTFE) technique was proposed by employing Grey level co-occurrence matrix (GLCM) and Gabor filters for identifying brain tumours.
Abstract: The effort of detecting brain tumours by radiologists or clinical experts is arduous and time-consuming, and their accuracy is dependent on their level of knowledge. Medical scans, such as magnetic resonance imaging (MRI), provide a wealth of data that can be exploited to overcome these constraints by creating advanced methodologies and approaches for tumour detection. These approaches can assist radiologists in offering a second opinion when predicting tumours, hence reducing the human aspect in the process. In this context, the paper proposes a hybrid texture-based feature extraction (HTFE) technique by employing Grey level co-occurrence matrix (GLCM) and Gabor Filters for identifying brain tumours. Specially, the proposed HTFE technique assists the classifiers Gradient Boosting (GB), Random Forest (RF), and Decision Tree (DT) in predicting Glioma, Meningioma, and Pituitary brain tumours from T1-weighted contrast-enhanced MRI (T1-CEMRI) dataset. To train and evaluate the classifiers, the HTFE technique extracts a total of seventy-two second order texture features from T1-CEMRI. In terms of accuracy, the suggested HTFE approach beats state-of-the-art techniques.

2 citations