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Overview of Research Projects

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Tumors develop in complex and dynamic microenvironments that influence their growth, invasion, and metastasis. The primary focus of our group is to utilize multidisciplinary approaches (molecular biology, bioinformatics, computational biology, nanotechnology, machine learning, and artificial intelligence) to understand the impact of the tumor microenvironment on tumor heterogeneity and the consequences for cancer cell plasticity, stemness, and therapy resistance.

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EMT-induced cells participate in tumor angiogenesisEMT enhances metastatic dissemination while partial EMT or reversal of EMT (MET or mesenchymal to epithelial transition) facilitates the growth of metastases. Our recent study showed that Carcinoma cells that have undergone an EMT differentiate into endothelial cells and contribute to tumor growth (Sphyris et al., 2021). Our findings link the stemness, conferred through EMT, to the acquisition of endothelial cell traits and the augmentation of tumor angiogenesis in an EMT-dependent manner. Currently, we are using in vitro as well as in vivo studies, to shed some light on the molecular mechanism of EMT-mediated endothelial transdifferentiation. EMT also plays a pivotal role in vasculogenic mimicry (a pattern of tumor microcirculation) formation. In reality, the coexistence of angiogenesis and VM is common within aggressive tumors. Angiogenesis inhibitors have little or even no effect on VM. Our study will identify the correlation between CSCs, EMT, and VM formation with a focus on breast cancer. 

VM in MDA231        VM in SUM 159

The Impact of Circadian disruption on Breast Tumorigenesis: In the breast, circadian clocks regulate the rhythmic expression of numerous genes. Circadian disruption is hypothesized to increase risk for breast cancer via disruption of central and peripheral clocks, resulting in widespread dysregulation of clock-controlled biological processes. Shift-work is an employment practice designed to provide services outside the traditional 9am-5pm working hours. Several epidemiological studies revealed that shift-work impacts human health and increases the risk of developing cancer, metabolic disorders, cardiovascular diseases, and mood disorders. Therefore, the aim of this work is to investigate the impact of shift-work in breast tumorigenesis and tumor microenvironment by using preclinical mouse models

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The role of Cancer-associated fibroblasts in tumor progression and therapy resistance: Cancer-associated fibroblasts have been implicated in diverse roles including cancer invasion, metastasis, resistance to existing cancer therapeutics, angiogenesis, and tumor proliferation. Using cutting-edge technologies, we will identify the different varieties of CAF and the complex interactions between CAFs and the various populations of neoplastic cells/immune cells in the tumor microenvironment with a focus on the involved pathways and genes. We will investigate how different types of CAF can interact with EMT plasticity of cancer cells, and conversely, how cancer cells exhibiting different phenotypes (epithelial vs. mesenchymal) can influence the properties of CAFs. We will use computational modeling of the crosstalk between CAFs and Tumor Cell Plasticity in the Tumor Microenvironment. This in silico system will help to acquire novel insights into designing effective therapeutic strategies aimed at cancer cells and/or CAFs.

Other projects:

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1.  Investigating the anti-cancer properties of novel nanomaterial

2. Investigating the anti-cancer properties of novel metabolite/vitamin derivative

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