Zohra Kalani
A5073541497- Glioma Diagnosis and Treatment
- CRISPR and Genetic Engineering
- Chromatin Remodeling and Cancer
- RNA and protein synthesis mechanisms
- Protein Degradation and Inhibitors
- Cancer Mechanisms and Therapy
- Single-cell and spatial transcriptomics
- GDF15 and Related Biomarkers
- RNA Research and Splicing
- Advanced biosensing and bioanalysis techniques
- Gene Regulatory Network Analysis
- Pluripotent Stem Cells Research
- Adipose Tissue and Metabolism
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- MicroRNA in disease regulation
- Cell Image Analysis Techniques
- Metabolism and Genetic Disorders
Broad Institute
2017-2023
Massachusetts Institute of Technology
2022
Abstract The role of PPM1D mutations in de novo gliomagenesis has not been systematically explored. Here we analyze whole genome sequences 170 pediatric high-grade gliomas and find that truncating increase the stability its phosphatase are clonal driver events 11% Diffuse Midline Gliomas (DMGs) enriched primary pontine tumors. Through development DMG mouse models, show potentiate activity is required for vivo oncogenesis. Finally, apply integrative phosphoproteomic functional genomics assays...
The CRISPR-Cas9 system has revolutionized gene editing both on single genes and in multiplexed loss-of-function screens, enabling precise genome-scale identification of essential to proliferation survival cancer cells. However, previous studies reported that an anti-proliferative effect Cas9-mediated DNA cleavage confounds such measurement genetic dependency, particularly the setting copy number gain 1-4 . We performed essentiality screens 342 cell lines found this is common all lines,...
A key question in genome research is whether biologically active proteins are restricted to the ∼20,000 canonical, well-annotated genes, or rather extend many non-canonical open reading frames (ORFs) predicted by genomic analyses. To address this, we experimentally interrogated 553 ORFs nominated ribosome profiling datasets. Of these ORFs, 57 (10%) induced a viability defect when endogenous ORF was knocked out using CRISPR/Cas9 8 human cancer cell lines, 257 (46%) showed evidence of protein...
<div>Abstract<p>Diffuse midline gliomas are uniformly fatal pediatric central nervous system cancers that refractory to standard-of-care therapeutic modalities. The primary genetic drivers a set of recurrent amino acid substitutions in genes encoding histone H3 (H3K27M), which currently undruggable. These H3K27M oncohistones perturb normal chromatin architecture, resulting an aberrant epigenetic landscape. To interrogate for dependencies, we performed CRISPR screen and show...
<div>Abstract<p>Diffuse midline gliomas are uniformly fatal pediatric central nervous system cancers that refractory to standard-of-care therapeutic modalities. The primary genetic drivers a set of recurrent amino acid substitutions in genes encoding histone H3 (H3K27M), which currently undruggable. These H3K27M oncohistones perturb normal chromatin architecture, resulting an aberrant epigenetic landscape. To interrogate for dependencies, we performed CRISPR screen and show...
Supplementary Figure from BAF Complex Maintains Glioma Stem Cells in Pediatric H3K27M
Supplementary Figure from BAF Complex Maintains Glioma Stem Cells in Pediatric H3K27M
Abstract Epigenetic dysregulation resulting in stalled development plays a crucial role pediatric cancer tumorigenesis. Diffuse midline gliomas (DMG) are universally fatal brain cancers refractory to standard of care treatment modalities. These malignancies driven by heterozygous mutations genes encoding histone 3 (H3K27M) which create an aberrant epigenetic landscape that keeps glioma cells undifferentiated stem-like state. Consequently, targeting regulators restore the epigenome and force...
Abstract Pediatric low-grade gliomas (pLGGs) are the most common solid tumors in children and associated with devastating lifelong morbidities mortality. Recent genomic profiling efforts have revealed that these largely driven by single-driver events activate MAPK signaling. These insights led to early clinical trials evaluating role of inhibitors for promising initial results. However, pLGGs not cured inhibitors, often rapidly rebound upon cessation treatment. Therefore, continuous dosing...