Biology subjects

Mura, M.

Publications and source records attributed to Mura, M..

3 recordsLinked to original sources

bioRxiv2026

WNT8B and -9B promote the survival and dissemination of dormant ovarian cancer cells

Cancer cell dormancy and the resultant resistance to conventional therapies present significant challenges for the successful treatment of high-grade serous ovarian cancer (HGSC). We used genome wide, and specialized sgRNA, libraries in CRISPR-based screens to identify critical cell survival mechanisms in dormancy and metastasis. Our findings demonstrate that low expression Wnt ligands WNT8B and WNT9B are essential for sustaining cell survival during prolonged dormant spheroid culture conditions. These Wnt ligands utilize non-canonical signaling to activate expression of stem cell genes such as ALDH1A1, CD44 and others during spheroid dormancy. The loss of WNT8B and WNT9B reduced survival of xenografted ovarian cancer cells during early dissemination of disease that extended survival. Furthermore, treatment of WNT8B/9B deficient xenografts with carboplatin demonstrated increased sensitivity that further reduced dissemination and extended survival. These findings reveal that rare Wnt ligands can possess outsized functions in cancer pathogenesis and offer new avenues for improving treatment outcomes for HGSC through their inhibition.

cancer biology↗

bioRxiv2025

Real-time Malaria Detection in the Amazon Rainforest via Drone-Collected eDNA and Portable qPCR

Emerging zoonotic parasites such as Plasmodium spp. in remote ecosystems demand rapid, field-deployable surveillance. We developed a drone-based environmental DNA (eDNA) sampling approach integrated with a portable quantitative PCR (qPCR) assay for in situ detection of Plasmodium DNA. Field trials confirmed malaria parasite DNA in canopy swabs, coinciding spatially with acoustic detection of howler monkeys (Alouatta sp.), suspected reservoir hosts. No Anopheles mosquitoes were captured in simultaneously deployed insect traps. The end-to-end workflow, from drone deployment to diagnostic readout, averaged 1.5 hours per assay, required only basic mobile-laboratory infrastructure, and bypassed cold-chain logistics. This rapid, non-invasive method delivers actionable surveillance data in real-time, enabling near-real-time trigger points for vector-control interventions and clinical response in remote settings. By merging environmental genomics with portable diagnostics, we establish a scalable One Health framework adaptable to diverse vector-borne parasites and ecosystems, with potential for early detection and spillover risk mitigation in under-monitored, high-risk environments.

molecular biology↗

bioRxiv2021

Use of hiPSC-derived cardiomyocytes to rule out proarrhythmic effects of drugs: the case of hydroxychloroquine in COVID-19

In the early phases of the COVID-19 pandemic, drug repurposing was widely used to identify compounds that could improve the prognosis of symptomatic patients infected by SARS-CoV-2. Hydroxychloroquine (HCQ) was one of the first drugs used to treat COVID-19 patients due to its supposed capacity of inhibiting SARS-CoV-2 infection and replication in vitro. While its efficacy is debated, HCQ has been associated with QT interval prolongation and potentially Torsades de Pointes, especially in patients predisposed to developing drug-induced Long QT Syndrome (LQTS) as silent carriers of variants associated with congenital LQTS. If confirmed, these effects represent a limitation to the at-home use of HCQ for COVID-19 infection as adequate ECG monitoring may be challenging. We investigated the proarrhythmic profile of HCQ with Multi-Electrode Arrays after subchronic exposure of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from two healthy donors, one asymptomatic and two symptomatic LQTS patients. We demonstrate that: I) HCQ induced a concentration-dependent Field Potential Duration (FPD) prolongation in vitro and triggered arrhythmias that halted the beating at high concentration. II) hiPSC-CMs from healthy or asymptomatic carriers tolerated higher concentrations of HCQ and showed lower susceptibility to HCQ-induced electrical abnormalities regardless of baseline FPD values. These findings agree with the clinical safety records of HCQ and demonstrated that hiPSC-CMs potentially discriminates symptomatic vs asymptomatic mutation carriers through pharmacological interventions. Disease-specific cohorts of hiPSC-CMs may be a valid preliminary addition to quickly assess drug safety in vulnerable populations, offering rapid preclinical results with valuable translational relevance for precision medicine.

physiology↗