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Biology subjects

Hemedan, A.

Publications and source records attributed to Hemedan, A..

3 recordsLinked to original sources

Applications of Boolean modeling to study the dynamics of a complex disease and therapeutics responses

Computational modeling has emerged as a critical tool in investigating the complex molecular processes involved in biological systems and diseases. In this study, we apply Boolean modeling to uncover the molecular mechanisms underlying Parkinsons disease (PD), one of the most prevalent neurodegenerative disorders. Our approach is based on the PD-map, a comprehensive molecular interaction diagram that captures the key mechanisms involved in the initiation and progression of PD. Using Boolean modeling, we aim to gain a deeper understanding of the disease dynamics, identify potential drug targets, and simulate the response to treatments. Our analysis demonstrates the effectiveness of this approach in uncovering the intricacies of PD. Our results confirm existing knowledge about the disease and provide valuable insights into the underlying mechanisms, ultimately suggesting potential targets for therapeutic intervention. Moreover, our approach allows us to parametrize the models based on omics data for further disease stratification. Our study highlight the value of computational modeling in advancing our understanding of complex biological systems and diseases, emphasizing the importance of continued research in this field. Furthermore, our findings have potential implications for the development of novel therapies for PD, which is a pressing public health concern. Overall, this study represents a significant step forward in the application of computational modeling to the investigation of neurodegenerative diseases, and underscores the power of interdisciplinary approaches in tackling challenging biomedical problems.

systems biology↗

A multi-omics integrative approach unravels novel genes and pathways associated with senescence escape after targeted therapy in NRAS mutant melanoma

Therapy Induced Senescence (TIS) leads to sustained growth arrest of cancer cells. The associated cytostasis has been shown to be reversible and cells escaping senescence further enhance the aggressiveness of cancers. Together with targeted therapeutics, senolytics, specifically targeting senescent cancer cells, constitute a promising avenue for improved cancer treatments. Understanding how cancer cells evade senescence is needed to optimise the clinical benefits of this therapeutic approach. Here we characterised the response of three different NRAS mutant melanoma cell lines to a combination of CDK4/6 and MEK inhibitors over 33 days. Transcriptomic data show that all cell lines trigger a senescence programme coupled with strong induction of interferons. Kinome profiling revealed the activation of Receptor Tyrosine Kinases (RTKs) and enriched downstream signaling of neurotrophin, ErbB and insulin pathways. Characterisation of the miRNA interactome associates miR-211-5p with resistant phenotypes. Finally, iCELL-based integration of bulk and single-cell RNA-seq data identified biological processes perturbed during senescence, and predicts new genes involved in its escape. Overall, our data associate insulin signaling with persistence of a senescent phenotype and suggest a new role for interferon gamma in senescence escape through the induction of EMT and the activation of ERK5 signaling.

cancer biology↗

A versatile and interoperable computational framework for the analysis and modeling of COVID-19 disease mechanisms

The COVID-19 Disease Map project is a large-scale community effort uniting 277 scientists from 130 Institutions around the globe. We use high-quality, mechanistic content describing SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing. Community-driven and highly interdisciplinary, the project is collaborative and supports community standards, open access, and the FAIR data principles. The coordination of community work allowed for an impressive step forward in building interfaces between Systems Biology tools and platforms. Our framework links key molecules highlighted from broad omics data analysis and computational modeling to dysregulated pathways in a cell-, tissue- or patient-specific manner. We also employ text mining and AI-assisted analysis to identify potential drugs and drug targets and use topological analysis to reveal interesting structural features of the map. The proposed framework is versatile and expandable, offering a significant upgrade in the arsenal used to understand virus-host interactions and other complex pathologies.

systems biology↗