Karla J. Cowley

RAD54L coordinates the nucleolar DNA damage response to maintain rDNA stability

Ruofei Liu, Jiachen Xuan, Carmelo Cerra, Nyree Stojnic et autres

The nucleolus is organized around actively transcribed ribosomal RNA genes (rDNA), where high RNA polymerase I (Pol I) activity creates intrinsic susceptibility to replication stress and DNA damage. Here, we identify the DNA translocase RAD54L as a critical regulator of the nucleolar …

au (code pays fourni par la source)

From complexity to clarity: Building dashboards for hit selection in high throughput screens

Karla J. Cowley, Hermione Allen, Kaylene J. Simpson

High throughput screening produces large, complex datasets that are difficult to interrogate without programming expertise, making hit selection time-consuming and inflexible. While instrument software and commercial tools offer partial solutions, they often lack adaptability or require costly infrastructure. Interactive dashboards provide an …

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Targeting DNA Methylation Reactivates Type I Interferon Signalling in Bone-Metastatic Breast Cancer

Joan So, Thomas B Chadwick, Miriam Fuentes, Laura Vojtech et autres

ABSTRACT Bone metastasis remains a major clinical challenge in advanced breast cancer. Downregulation of type I interferon signalling, a critical immunomodulatory pathway in anti-cancer immunity and disease progression, is a defining feature of this process. Here, we utilised an IFN-reporter system to …

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Identifying therapeutic targets in low‐grade serous ovarian carcinomas with no specific molecular profile

Kathleen I. Pishas, Karla J. Cowley, Evanny Marinovic, Martin Köbel et autres

Low-grade serous ovarian carcinoma (LGSOC) is a rare, indolent ovarian cancer subtype with limited effective therapies. Approximately 40% of cases lack canonical MAPK/ERK or PI3K/AKT/mTOR pathway alterations and are classified as having no specific molecular profile (NSMP). These patients have poor responses …

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A scalable, multi-resolution consensus clustering approach for prioritizing robust signals from high-throughput screens

Shaine Chenxin Bao, Kathleen I. Pishas, Karla J. Cowley, Qiongyi Zhao et autres

Modern biology increasingly relies on large-scale screening to generate high dimensional datasets with potential to accelerate discovery. However, analysing these complex datasets remains challenging, due to hierarchical biological structure, uncertainty in the true number of groups, and high dimensional noise that confounds …

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Comprehensive drug efficacy data for mucinous ovarian carcinoma using a novel and extensive biobank of patient-derived organoid models

Olivia Craig, Carolina Salazar, Suad M. Abdirahman, Nikita Dalvi et autres

Abstract Mucinous Ovarian Carcinoma (MOC) is a rare ovarian cancer histological subtype with distinct pathology, genomics and clinical outcomes compared to other epithelial ovarian cancers. Accordingly, there is little evidence to guide clinical care, particularly in the use of systemic therapies, and …

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Differential Preclinical Efficacy of Combined CDK4/6 and MEK Inhibition in Low-Grade Serous Ovarian Carcinoma Based on KRAS/NF1 Mutational Status

Madison Bittner, Marta Llauradó Fernández, Joshua Hoenisch, Y Leung et autres

Low-grade serous ovarian carcinoma (LGSOC) usually presents in advanced stages and is associated with a high mortality rate. Clinical trials targeting the MAPK and cell cycle pathways in LGSOC have shown promising results for its treatment, however there is a need to …

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Differential Preclinical Efficacy of Combined CDK4/6 and MEK Inhibition in Low-Grade Serous Ovarian Carcinoma Based on KRAS/NF1 Mutational Status

Madison Bittner, Marta Llaurado Fernandez, Joshua Hoenisch, Y Leung et autres

Low-grade serous ovarian carcinoma (LGSOC) usually presents in advanced stages and is associated with a high mortality rate. Clinical trials targeting the MAPK and cell cycle pathways in LGSOC have shown promising results for its treatment, however there is a need to …

Exploiting dysregulated iron homeostasis to eradicate persistent high-grade serous ovarian cancer

Carmelo Cerra, Madeleine R. C. Tancock, Niko Thio, Ada Koo et autres

Treatments for high-grade serous ovarian cancer (HGSOC) are initially effective but most invariably fail. Although they can successfully suppress the bulk of the tumour cell population, residual cancer cells can enter alternative therapy-resistant cell fates highlighted by proliferative arrest. Understanding the nature …

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Genome-wide analysis of host-encoded microRNAs modulating SARS-CoV-2 infection

Christina L. Rootes, Karla J. Cowley, Aaron M. Brice, Henry G. Beetham et autres

Viruses exploit cellular machinery to complete their replication cycle. Furthering our understanding of this process provides insight into the mechanism of virus replication and potential targets for antiviral therapeutics. Genome-wide CRISPR screens have identified cellular pathways important in the SARS-COV-2 infection process, …

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Local nucleolar surveillance mechanisms maintain rDNA stability

Ruofei Liu, Jiachen Xuan, Shalini Sundramurthi Chelliah, Rhynelle Dmello et autres

Abstract The nucleoli are subdomains of the nucleus that form around actively transcribed ribosomal RNA (rRNA) genes. The highly repetitive and transcribed nature of the rRNA genes (rDNA) by RNA polymerase I (Pol I) poses a challenge for DNA repair and replication …

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High-throughput drug screening identifies novel therapeutics for Low Grade Serous Ovarian Carcinoma

Kathleen I. Pishas, Karla J. Cowley, Marta Llaurado-Fernandez, Hannah Kim et autres

Low grade serous carcinoma (LGSOC) is a rare epithelial ovarian cancer with unique molecular characteristics compared to the more common tubo-ovarian high-grade serous ovarian carcinoma. Pivotal clinical trials guiding the management of epithelial ovarian cancer lack sufficient cases of LGSOC for meaningful …

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