Biology subjects

Suleymanova, I.

Publications and source records attributed to Suleymanova, I..

4 recordsLinked to original sources

bioRxiv2025

Microtubule Inhibition Triggers MYC-Mediated Immunogenic Cell Death in Breast Cancer

Oncogenic MYC promotes cancer cell proliferation, metabolism, and death, while also driving immunosuppression in the tumour microenvironment, complicating immune-based therapies. To counter MYC-driven immune evasion while leveraging MYC-dependent synthetic lethality (MYC-SL), we identified microtubule-targeting agents, including eribulin, as potent inducers of immunogenic cell death in MYChigh triple-negative breast cancer (TNBC). A screen of 528 oncology compounds using damage-associated molecular pattern (DAMP) reporters revealed that microtubule inhibitors induced key DAMPs, including HMGB1 secretion, calreticulin exposure, and double-stranded DNA release, leading to gasdermin-E associated cell death in MYChigh TNBCs. Immune cell co-culture assays showed immune activation, and patient-derived explant cultures confirmed pro-inflammatory cytokine responses. In vivo, cell-free media from eribulin-treated MYChigh murine TNBCs enhanced tumour protection in vaccination models compared to MYC-knockdown controls, linking MYC-dependent DAMP release to immunogenicity. These findings highlight a dual-function therapeutic strategy: agents that selectively induce MYC-dependent immunogenic cell death can provide both targeted cytotoxicity and local immune stimulation, thereby addressing a key limitation of conventional chemotherapeutics, offering a new approach for MYC-driven cancers.

cancer biology↗

bioRxiv2024

Chronic treatment with fluoxetine downregulates mitochondrial activity in parvalbumin interneurons of prefrontal cortex

Chronic treatment with fluoxetine, a widely prescribed selective serotonin reuptake inhibitor (SSRI), is known to promote neural plasticity. The role of fluoxetine in plasticity has been particularly tied to parvalbumin-positive interneurons (PV-INs), which are critical regulators of inhibitory tone and synaptic plasticity. Our previous studies have highlighted behavioral plasticity and gene expression changes in the visual cortex and hippocampus after chronic treatment with fluoxetine. However, the impact of fluoxetine treatment on gene expression and neuronal function in the prefrontal cortex (PFC) remains unclear. This study aimed to investigate the effects of chronic fluoxetine treatment on PV-INs in the PFC. Using Translating Ribosome Affinity Purification (TRAP), we found that fluoxetine treatment downregulated pathways involved in mitochondrial energy production, including multiple steps of the respiratory chain. Upregulated genes were associated with phosphatase activity, voltage-gated potassium channels, and amino acid transmembrane transport. Mitochondrial analysis for sorted cells demonstrated mitochondrial membrane potential was reduced in PV-INs, but increased in non-PV-INs in the PFC. These observations indicate altered mitochondrial dynamics between the cell types and reduced mitochondrial activity in PV-INs, potentially contributing to their disinhibition. Immunohistochemical analyses further demonstrated reduced PV expression and weakened perineuronal nets in specific PFC regions, suggesting elevated plasticity, and potentially explaining the modulation of fear and anxiety-related behaviors that were previously observed. Our results underscore the differential impact of chronic fluoxetine on gene expression and mitochondrial function in PV-INs, suggesting region-specific disinhibition and enhanced synaptic plasticity in the PFC.

neuroscience↗

bioRxiv2023

Respiratory Complex I Regulates Dendritic Cell Maturation in Explant Model of Human Tumor Immune Microenvironment

Combining cytotoxic chemotherapy or novel anticancer drugs with T-cell modulators holds great promise in treating advanced cancers. However, the response varies depending on the tumor immune microenvironment (TIME). Therefore, there is a clear need for pharmacologically tractable models of the TIME to dissect its influence on mono- and combination treatment response at the individual level. Here we establish a Patient-Derived Explant Culture (PDEC) model of breast cancer, which retains the immune contexture of the primary tumor, recapitulating cytokine profiles and CD8+ T cell cytotoxic activity. We explored the immunomodulatory action of a synthetic lethal BCL2 inhibitor venetoclax + metformin drug combination ex vivo, discovering metformin cannot overcome the lymphocyte-depleting action of venetoclax. Instead, metformin promotes dendritic cell maturation through inhibition of mitochondrial complex I, increasing their capacity to co-stimulate CD4+ T cells and thus facilitating anti-tumor immunity. Our results establish PDECs as a feasible model to identify immunomodulatory functions of anticancer drugs in the context of patient-specific TIME.

cancer biology↗

bioRxiv2017

A deep convolutional neural network approach for astrocyte detection

Astrocytes are involved in brain pathologies such as trauma or stroke, neurodegenerative disorders like Alzheimers and Parkinsons disease, chronic pain, and many others. Determining cell density and timing of morphological and biochemical changes is important for a proper understanding of the role of astrocytes in physiological and pathological conditions. One of the most important of such analyses is astrocytes count within a complex tissue environment in microscopy images. The most widely used approaches for the quantification of microscopy images data are either manual stereological cell counting or semi-automatic segmentation techniques. Detecting astrocytes automatically is a highly challenging computational task, for which we currently lack efficient image analysis tools. In this study, we developed a fast and fully automated software that assesses the number of astrocytes using Deep Convolutional Neural Networks (DCNN). The method highly outperforms state-of-the-art image analysis and machine learning methods and provides detection accuracy and precision comparable to that of human experts. Additionally, the runtime of cell detection is significantly less than other three analyzed computational methods, and it is faster than human observers by orders of magnitude. We applied DCNN-based method to examine the number of astrocytes in different brain regions of rats with opioid-induced hyperalgesia/tolerance (OIH/OIT) as morphine tolerance is believed to activate glial cells in the brain. We observed strong positive correlation between manual cell detection and DCNN-based analysis method for counting astrocytes in the brains of experimental animals.

bioinformatics↗