Publications by authors named "Jyothishmathi Swaminathan"
The RE1 silencing transcription factor (REST) is a driver of sonic hedgehog (SHH) medulloblastoma genesis. Our previous studies showed that REST enhances cell proliferation, metastasis and vascular growth and blocks neuronal differentiation to drive progression of SHH medulloblastoma tumors. Here, we demonstrate that REST promotes autophagy, a pathway that is found to be significantly enriched in human medulloblastoma tumors relative to normal cerebella.
View Article and Find Full Text PDFMapping the Single-Cell Differentiation Landscape of Osteosarcoma.
Clin Cancer Res
August 2024
Article Synopsis
- * Researchers profiled over 31,000 cells to create a differentiation map of mesenchymal stem cells, revealing insights into how they develop into various cell types.
- * The findings suggest a link between certain stem-like cell characteristics and poor survival, highlighting the potential for targeted therapies aimed at overcoming differentiation issues in osteosarcoma.
Article Synopsis
- Single-cell RNA sequencing (scRNA-seq) is a powerful tool for analyzing complex tissues and understanding individual cell types, but it can introduce biases in gene expression due to tissue processing methods.
- The study focused on sarcomas, specifically three aggressive subtypes (osteosarcoma, Ewing sarcoma, and desmoplastic small round cell tumor), and evaluated how different cell dissociation techniques affect gene expression results.
- Findings revealed significant transcriptional biases from various dissociation methods, but classic sarcoma gene signatures remained detectable, indicating that these biases can be corrected computationally.
The Silencing Transcription Factor (REST) is a major regulator of neurogenesis and brain development. Medulloblastoma (MB) is a pediatric brain cancer characterized by a blockade of neuronal specification. gene expression is aberrantly elevated in a subset of MBs that are driven by constitutive activation of sonic hedgehog (SHH) signaling in cerebellar granular progenitor cells (CGNPs), the cells of origin of this subgroup of tumors.
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- * A study discovered that HGG has a higher than normal rate of alternative splicing, which is linked to worse patient prognosis and surpasses mutation rates in cancer drivers.
- * The research showed that altered splicing of important cancer pathways, particularly the RAS/MAPK pathway, contributes to tumor growth and decreased survival, highlighting the need for personalized medicine to address these non-mutational mechanisms.
Article Synopsis
- Studies show that DNA-protein interactions play crucial roles in regulating processes like replication, repair, and transcription, affecting gene expression and potentially leading to tumors.
- Chromatin immunoprecipitation assay (ChIP) is the primary method used to study DNA-binding in living organisms and has become essential in cancer research.
- The article focuses on using ChIP with a pediatric medulloblastoma cell line (DAOY) to analyze transcription factors, histone modifications, and discover new therapeutic targets.
Expression of the RE1-silencing transcription factor (REST), a master regulator of neurogenesis, is elevated in medulloblastoma (MB) tumors. A cell-intrinsic function for REST in MB tumorigenesis is known. However, a role for REST in the regulation of MB tumor microenvironment has not been investigated.
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- Functional genomics provides dense genome-wide signal profiles that help identify regulatory elements, particularly focusing on valley patterns seen in assays like ChIP Sequencing, which pinpoint locations of cis-regulatory elements but are often overlooked in analysis.
- EpiSAFARI is a new computational method designed to detect these valleys with high accuracy by reducing noise in signal profiles and considering various factors such as signal sparsity and nucleotide content.
- The method shows that histone valleys are highly conserved and linked to transcription factor binding and transcription activity, particularly at gene promoters, and is available for use on GitHub.
Article Synopsis
- The study focuses on medulloblastomas (MBs) driven by the sonic hedgehog (SHH) pathway, highlighting the increased expression of the RE1-silencing transcription factor (REST) in the SHH-α and SHH-β subgroups, which are associated with poor patient outcomes.
- Using a transgenic mouse model, researchers found that REST interacts with GLI1, impacting tumor growth and neuronal maturation, notably showing a greater neuronal maturity in SHH-β tumors.
- Results indicate that REST contributes to chromatin remodeling and AKT activation in MBs, suggesting potential subgroup-specific therapeutic strategies for treating patients with these tumors.
Article Synopsis
- * The study demonstrates that USP37 can inhibit medulloblastoma growth in mouse models, highlighting its potential as a tumor suppressor in this type of cancer.
- * The repression of USP37 is linked to the silencing transcription factor REST, which works with the histone methyltransferase G9a to modify histone proteins, suggesting that targeting G9a could reactivate USP37 and serve as a therapeutic strategy for certain medulloblastomas.
Effects of local mRNA structure on posttranscriptional gene silencing.
Proc Natl Acad Sci U S A
September 2008
Article Synopsis
- * AONs are less sensitive to the structure of the mRNA, meaning they can work well even when the target has unpaired nucleotides, while siRNAs require more accessible sequences for efficient cleavage.
- * However, in live organisms, siRNAs were found to silence their target genes more efficiently than AONs, suggesting that other factors, like RNA-binding proteins such as alphaCP, play a crucial role in the
Regulating gene expression in human leukemia cells using light-activated oligodeoxynucleotides.
Nucleic Acids Res
February 2008
Article Synopsis
- Researchers created light-sensitive oligodeoxynucleotides (asODNs) to degrade target mRNA in cells using a technique that relies on UV light activation.
- A specific asODN targeting c-myb was attached to complementary strands, which kept it inactive until exposed to UV light, leading to effective mRNA degradation in tested leukemia cells.
- The study identified that one conjugate, C6, was thermally stable and had the lowest initial degradation rate but showed significant RNA digestion post-UV activation, enhancing the potential for controlled gene regulation in living cells.
Activation and repression of transcription in eukaryotes involve changes in the chromatin fiber that can be accomplished by covalent modification of the histone tails or the replacement of the canonical histones with other variants. Here we show that the histone H2A variant of Drosophila melanogaster, H2Av, localizes to the centromeric heterochromatin, and it is recruited to an ectopic heterochromatin site formed by a transgene array. His2Av behaves genetically as a PcG gene and mutations in His2Av suppress position effect variegation (PEV), suggesting that this histone variant is required for euchromatic silencing and heterochromatin formation.
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