Publications by authors named "Kathleen H Burns"
LINE-1 (L1) retrotransposition is widespread in many cancers, especially those with a high burden of chromosomal rearrangements. However, whether and to what degree L1 activity directly impacts genome integrity is unclear. Here, we apply whole-genome sequencing to experimental models of L1 expression to comprehensively define the spectrum of genomic changes caused by L1.
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- Direct methods for assessing DNA polymerase fidelity are straightforward, but measuring RNA polymerases and reverse transcriptases is trickier due to extra preparation steps that can lead to errors.
- The new method, Roll-Seq, uses single molecule real-time sequencing to evaluate the fidelity of RNA polymerases and reverse transcriptases simultaneously, by generating long concatemeric cDNA from a circular RNA template.
- Roll-Seq results showed that while some reverse transcriptases had consistent substitution rates, others demonstrated lower fidelity during second-strand synthesis, highlighting the importance of RNA structure on polymerase accuracy.
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- The Johns Hopkins Physician-Scientist Training Program (PSTP) aims to address issues in training and retaining physician-scientists by offering seminars, mentorship, and funding opportunities to residents and fellows.
- A study evaluating the PSTP from 2017-2020 found that 41% of its scholars were women, with a significant portion identifying as minorities, and many scholars receiving research support.
- Most graduates remained in academia, indicating that the PSTP effectively provides the resources and mentor connections necessary to foster careers as physician-scientists.
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- The LINE-1 retrotransposon is a significant genetic element in humans, contributing to about a third of our genome via a 'copy and paste' method driven by its enzyme, ORF2p, which is linked to diseases like cancer and autoimmunity.
- Recent studies using X-ray crystallography and cryo-electron microscopy have revealed new structural details of ORF2p, including previously unknown domains and a dynamic conformation that changes during the retrotransposition process.
- The findings enhance our understanding of L1 replication and its effects on immune responses, creating potential pathways for drug development targeting L1 and related cellular processes.
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- LINE-1 is the only active protein-coding transposon in humans that uses RNA to insert itself into different locations in the genome, making up about 20% of our DNA.
- Most LINE-1 copies are inactive, but around 100 can move and are linked to the development of cancer due to their overexpression and retrotransposition.
- The text reviews how LINE-1 is regulated, its role in increasing genetic diversity in tumors, and potential treatments that could target LINE-1 activity in cancer therapies.
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- The conference on "Transposable Elements at the Crossroads of Evolution, Health and Disease" took place in Whistler, Canada, from September 3-6, 2023, organized by experts Kathleen Burns, Harmit Malik, and Irina Arkhipova.
- It focused on the diverse interactions of transposable elements (TEs) with host organisms, exploring their potential to disrupt genes and promote evolutionary changes through novel gene products and functions.
- The event featured six plenary sessions, two workshops, 50 talks, and poster sessions, covering both normal and pathological roles of TEs, as well as strategies to manage their activity through various scientific approaches.
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- The first Dark Genome Symposium took place in November 2022 in Boston, organized by biotech companies Rome Therapeutics and Enara Bio to discuss advancements in genetic research and its potential for treating diseases.
- The event featured welcoming speeches, defining talks by leading academics, and panels that combined perspectives from both academia and industry on various related topics.
- Richard Young and David Ting concluded the meeting by sharing insights on how the ongoing research into the Dark Genome could positively affect patient outcomes in the future.
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- Frontline treatments for advanced ovarian cancer have seen little improvement in cure rates over many years.
- The text emphasizes the need for a multidisciplinary strategy to explore new therapeutic options.
- It highlights the importance of understanding minimal residual disease, which is the phase that contributes to recurring and eventually incurable ovarian cancer.
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- Vitamin C (vitC) enhances the activity of enzymes involved in DNA and histone demethylation, promoting better stem cell development and maintaining pluripotency in embryonic stem cells.
- Research shows that vitC increases the expression of certain transposable element families, particularly young LINE-1 (L1) elements, in mouse embryonic stem cells.
- Despite the rise in L1 levels from vitC treatment, no increase in somatic insertion rates was observed, indicating that vitC modifies transposable element expression without causing more frequent mutations.
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- * This study analyzed over 3,600 whole-genome sequencing samples to create a catalog of variable SVA insertions and included detailed characterizations of their structures and activities in different human populations.
- * The research improves the understanding and identification of SVA elements, enabling better genetic analysis and aiding in the discovery of harmful SVA insertions linked to various diseases.
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- * The LINE-1 ORF1p protein is overexpressed in various cancers and has negligible expression in normal tissues, indicating its potential as a highly specific blood-based cancer biomarker.
- * Advanced digital immunoassays can detect low levels of ORF1p in plasma, showing promise for early detection of ovarian cancer and monitoring treatment responses in gastroesophageal cancers, suggesting it could be a valuable tool for cancer diagnosis and prognosis.
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- The study evaluated an algorithmic testing approach in hematopathology to enhance cost-effectiveness in test selection at Brigham and Women's Hospital and Dana-Farber Cancer Institute, especially for expensive molecular assays.
- Researchers developed standard ordering protocols (SOPs) for 17 disease categories, comparing data from six months of beta testing to actual testing practices, along with two years of prospective data from a community site.
- Results showed a massive improvement in test concordance after implementing SOPs, with a decrease in overordered tests and significant potential annual savings of over $1.3 million, indicating that algorithmic testing can streamline procedures without compromising vital information.
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- Transposable elements (TEs) are usually silenced in healthy tissues by DNA methylation but become more active in various cancers, correlating with global hypomethylation in those cancer genomes.
- The study examined TE expression and DNA methylation during the transformation of fibroblast cells, showing that TE expression significantly increased at each transformation stage, particularly after the final stage, mirroring observations in human tumors.
- The research highlighted that hypomethylation of TEs started during the immortalization phase and continued into the transformation, with many upregulated TEs being linked to cancers in The Cancer Genome Atlas dataset.
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- * The Long INterspersed Element-1 (LINE-1) open reading frame 1 protein (ORF1p) is found to be overexpressed in various cancers but not in normal tissues, highlighting its potential as a specific cancer biomarker.
- * Researchers have developed highly sensitive digital immunoassays to detect ORF1p in blood samples, showing promise for early detection of ovarian cancer and improved monitoring of gastric and esophageal cancers, positioning it as a valuable multi-cancer biomarker.
Long interspersed element 1 (LINE-1) open reading frame 1 protein (ORF1p) expression is a common feature of many cancer types, including high-grade serous ovarian carcinoma (HGSOC). Here, we report that ORF1p is not only expressed but also released by ovarian cancer and primary tumor cells. Immuno-multiple reaction monitoring-mass spectrometry assays showed that released ORF1p is confidently detectable in conditioned media, ascites, and patients' plasma, implicating ORF1p as a potential biomarker.
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- - Transposable elements (TEs) may increase the risk of neuropsychiatric diseases as they are active in neuronal cells, but traditional genome-wide association studies (GWAS) typically overlook these structural variants.
- - In a study involving 17,000 polymorphic TEs, researchers found 76 that are linked to disease haplotypes identified by GWAS, suggesting a connection between TEs and neuropsychiatric conditions.
- - Among these, 10 specific TE insertions showed potential regulatory effects on gene expression in human neural stem cells, indicating they could play a causal role in neurological and psychiatric disorders.
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- CRISPR/Cas9 has transformed molecular biology and entered gene therapy, making it important to track DNA changes for safe and effective editing.
- Researchers found that LINE-1 retrotransposons can frequently insert themselves at CRISPR/Cas9 target sites, demonstrating over 2500 new insertions in various cell types.
- Unlike CRISPR/Cas9, other editing methods like prime editors and base editors result in rare L1 insertions due to lower DNA break rates, highlighting differences in safety profiles among these editing tools.
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- Transposons, also known as "jumping genes," are segments of DNA that can move around within the genome, which raises questions about their role in genetics and evolution.
- In biomedical research, scientists are increasingly interested in understanding how transposons affect gene expression and potentially contribute to diseases.
- The attention on transposons leads to new insights into their functions, as well as their potential use in gene therapy and other medical applications.
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- Altered RNA expression and retrotransposition of repetitive sequences play a significant role in the progression of colorectal cancer, particularly in cells with p53 mutations.
- The nucleoside reverse transcriptase inhibitor 3TC was shown to target these repeat elements effectively, resulting in clinical benefits for some patients in a phase II trial.
- The study highlights a new cancer treatment strategy by exploiting the viral-like behavior of repeat sequences, using NRTIs to induce DNA damage and activate immune responses against colorectal cancer.
Retrotransposons are genomic DNA sequences that copy themselves to new genomic locations via RNA intermediates; LINE-1 is the only active and autonomous retrotransposon in the human genome. The mobility of LINE-1 is largely repressed in somatic tissues but is derepressed in many cancers, where LINE-1 retrotransposition is correlated with p53 mutation and copy number alteration (CNA). In cell lines, inducing LINE-1 expression can cause double-strand breaks (DSBs) and replication stress.
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- Tumor surface marker expression influences treatment choices, outcomes, and patient survival, but traditional biopsies are invasive and often miss important variations within tumors.
- Researchers studied antibody-conjugated SERRS-NPs to visualize and measure surface markers like EGFR and HER2 in tumors, comparing their effectiveness in both intracranial and peripheral tumor models.
- The SERRS-NP imaging technique provided distinct Raman signals that accurately distinguished levels of surface marker expression, suggesting it could be a non-invasive alternative to biopsies and improve molecular imaging accuracy in clinical settings.
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- High copy number interspersed repeats near genes have evolved in humans and can lead to significant structural variations in the genome.
- This study investigates how these insertion variants affect gene expression, using luciferase reporter assays to assess their regulatory impacts.
- Findings reveal that these polymorphic insertions can influence gene expression linked to cancer risk, highlighting their potential role in disease susceptibility.