Alisha Kardian
A5041037068- Glioma Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Circular RNAs in diseases
- PARP inhibition in cancer therapy
- Ferroptosis and cancer prognosis
- MicroRNA in disease regulation
- RNA Research and Splicing
- Protein Degradation and Inhibitors
- Neuroscience and Neuropharmacology Research
- Nerve injury and regeneration
- Neurogenesis and neuroplasticity mechanisms
- Cancer, Hypoxia, and Metabolism
- Cancer, Lipids, and Metabolism
- Bone Tumor Diagnosis and Treatments
- Testicular diseases and treatments
- Sarcoma Diagnosis and Treatment
- RNA modifications and cancer
- Radiopharmaceutical Chemistry and Applications
- Histone Deacetylase Inhibitors Research
- Cancer Genomics and Diagnostics
- Chromatin Remodeling and Cancer
- Adipose Tissue and Metabolism
- Memory and Neural Mechanisms
- Signaling Pathways in Disease
- Genomics and Chromatin Dynamics
Baylor College of Medicine
2021-2025
St. Jude Children's Research Hospital
2023-2025
Lieber Institute for Brain Development
2015-2022
Johns Hopkins Medicine
2015-2022
Johns Hopkins University
2015-2022
Children's Cancer Center
2021
Dan L Duncan Comprehensive Cancer Center
2021
Johns Hopkins Bayview Medical Center
2020
Abstract More than 60% of supratentorial ependymomas harbor a ZFTA–RELA (ZRfus) gene fusion (formerly C11orf95–RELA). To study the biology ZRfus, we developed an autochthonous mouse tumor model using in utero electroporation (IUE) embryonic brain. Integrative epigenomic and transcriptomic mapping was performed on IUE-driven ZRfus tumors by CUT&RUN, chromatin immunoprecipitation sequencing, assay for transposase-accessible RNA sequencing compared with human ZRfus-driven ependymoma. In...
Abstract Posttraumatic stress disorder is characterized by hyperarousal, sensory processing impairments, sleep disturbances and altered fear regulation; phenotypes associated with changes in brain oscillatory activity. Molecules activity-dependent plasticity, including brain-derived neurotrophic factor (BDNF), may regulate neural oscillations controlling synaptic BDNF synthesis includes production of multiple Bdnf transcripts, which contain distinct 5′ noncoding exons. We assessed arousal,...
Ependymoma (EPN) is a common form of brain tumor in children, often resistant to available cytotoxic therapies. Molecular profiling studies have led better understanding EPN subtypes and revealed critical role oncogenes ZFTA–RELA fusion EPHB2 supratentorial ependymoma (ST-EPN). However, the immune system’s progression response therapy remains poorly understood. New treatments for various molecular are desperately needed. Using ST-EPN-ZFTA subtype-specific syngeneic mouse models, we found an...
Brain-derived neurotrophic factor (BDNF) is a key neuropeptide in the central regulation of energy balance. The Bdnf gene contains nine promoters, each producing specific mRNA transcripts that encode common protein. We sought to assess phenotypic outcomes disrupting BDNF production from individual promoters. Mice with an intact coding region but selective disruption promoters I, II, IV, or VI (Bdnf-e1-/-, -e2-/-, -e4-/-, and -e6-/-) were created by inserting enhanced green fluorescent...
Brain-derived neurotrophic factor (BDNF) signals through its cognate receptor tropomyosin kinase B (TrkB) to promote the function of several classes inhibitory interneurons. We previously reported that loss BDNF-TrkB signaling in cortistatin (Cort)-expressing interneurons leads behavioral hyperactivity and spontaneous seizures mice. performed bulk RNA sequencing (RNA-seq) from cortex mice with disruption interneurons, identified differential expression genes important for excitatory neuron...
Abstract BACKGROUND Pediatric ependymoma is a malignant brain tumor without targeted therapies. The 10-year survival close to 50%, as this relentless often relapses years following initial diagnosis. Over two thirds of supratentorial ependymomas harbor gene fusion between ZFTA and RELA (ZFTA-RELA). Despite evidence that ZFTA-RELA drives tumorigenicity, mechanistic details remain elusive, hindering efforts uncover therapeutic vulnerabilities. Since direct targeting not currently possible, we...
ABSTRACT ZFTA-RELA is the most recurrent genetic alteration seen in pediatric supratentorial ependymoma (EPN) and sufficient to initiate tumors mice. Despite ZFTA-RELA’s potent oncogenic potential, gene fusions are observed exclusively childhood EPN, with located distinctly region of central nervous system (CNS). We hypothesized that specific chromatin modules accessible during brain development would render distinct cell lineage programs at direct risk transformation by ZFTA-RELA. To this...
<h3>Background</h3> Targeted treatment options are desperately needed for ependymoma (EPN), a highly aggressive pediatric brain tumor. Chimeric antigen receptor (CAR) T-cells have immense potential to transform outcomes. However, little is known regarding the antitumor efficacy of CAR against EPNs. We previously found that B7-H3 and consistently expressed on EPN patient samples, making it promising T-cell target. Here, we established indeed an effective anti-EPN target, but were less in...
<title>Abstract</title> Over 95% of EPNs that arise in the cortex are driven by a gene fusion involving zinc finger translocation associated (ZFTA) protein. Using super-resolution and lattice light sheet microscopy, we demonstrate most frequent variant, ZFTA-RELA(ZR), forms dynamic nuclear condensates required for oncogene expression tumorigenesis. Mutagenesis ZR reveals key intrinsically disordered regions (IDRs) govern condensate formation. Condensate-modulating IDR mutations impaired...
Abstract BACKGROUND Ependymomas continue to be an aggressive brain tumor entity without targeted therapies. The highly recurrent fusion oncoprotein (FO), ZFTA-RELA, is known associated with about 70% of supratentorial ependymomas. While recent studies have highlighted that the protein involved in aberrant DNA binding and subsequent oncogenic gene expression, precise mechanisms underlying transcriptional dysregulation remain elusive. METHODS Using super-resolution lattice-sheet microscopy, we...
<div>Abstract<p>More than 60% of supratentorial ependymomas harbor a <i>ZFTA–RELA</i> (ZR<sup>fus</sup>) gene fusion (formerly <i>C11orf95–RELA</i>). To study the biology ZR<sup>fus</sup>, we developed an autochthonous mouse tumor model using <i>in utero</i> electroporation (IUE) embryonic brain. Integrative epigenomic and transcriptomic mapping was performed on IUE-driven ZR<sup>fus</sup> tumors by...
<p>Figure S5 to show gene and protein expression patterns of ZRfus as well genomic localization signatures.</p>
<p>Figure S6 to show up-regulation of the NF-kB pathway in ZRfus IUE tumors</p>
<p>Figure S3 demonstrating transcriptional alterations as a result of ZRfus loss function</p>
<p>CRCs detected in mouse IUE ZRfus1 driven ependymoma</p>
<p>Figure S2 supporting expression and localization of ZRfus in the mouse IUE model.</p>
<p>HA-ZRfus1 bound and over-expressed genes compared to mouse normal brain</p>
<p>DNA motifs detected and shared with mouse embryonic fibroblasts treated TNF-alpha</p>
<p>Figure S4 to show supporting data of DNA motif finding in ZRfus specific binding sites.</p>
<p>Summary of oligos and sgRNA sequences used in the study</p>
<p>93 gene signature that characterizes ZFTA-Rela mouse and human tumors.</p>