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Survival of Cancer Stem Cells: a good opportunity in bad neighbourhood


   School of Science, Engineering and Environment

   Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Cancers are not just masses of malignant cells but complex ‘rogue’ organs, to which many other cells are recruited and can be corrupted. Interactions between malignant and non- cells create the tumor-microenvironment (TME). The non-malignant cells of TME have a dynamic and often tumor-promoting function at all stages of carcinogenesis. Tumours originating in the bone marrow often contain a complex mixture of cancerous and non-cancerous cell types including endothelial cells, neuronal cells, and blood vessels (Calvo and Sahai, 2011, Egeblad et al., 2010). Cancer-associated fibroblasts (CAFs) are pathological active non-malignant cells associated with many tumours, favouring tumour aggressiveness (Ohlund et al., 2014). CAFs represent an attractive therapeutic target for clinical intervention (Quail and Joyce, 2013). Such pathologically active status of CAFs is poorly understood. This study will shed light on communication molecules between malignant cells and non-malignant yet tumour-promoting CAFs. Understanding communication molecules can change the therapeutic strategy in cancers. Cancers (Stem) cell have an intricate network of cells in microenvironment to maintain and protect such cells. Interactions between malignant and non-malignant cells create the tumour-microenvironment (TME). The non-malignant cells of TME have a dynamic and often tumour-promoting function at all stages of carcinogenesis. Tumours originating in the bone marrow often contain a complex mixture of cancerous and non-cancerous cell types including endothelial cells, neuronal cells, and blood vessels (Calvo and Sahai, 2011, Egeblad et al., 2010). Cancer-associated fibroblasts (CAFs) are pathological active non-malignant cells associated with many tumours, favouring tumour aggressiveness (Ohlund et al., 2014). CAFs represent an attractive therapeutic target for clinical intervention (Quail and Joyce, 2013). Such pathologically active status of CAFs is poorly understood. This study will shed light on communication molecules between malignant cells and non-malignant yet tumour-promoting CAFs. Understanding communication molecules can change the therapeutic strategy in cancers.

This proposal will investigate the role of malignant haematopoietic stem and progenitor cells in regulating the growth of neighbouring fibroblasts which inturn support the growth of malignant cells in tit-for-tat fashion.

By integrating gene expression data of model CAF and a candidate-driven functional screening, we will identify genes that are commonly dysregulated in CAFs in leukaemia. We will further investigate the relevance of such genes in CAF functions and delineate its mechanism of action using virally transduced expression analysis changes in malignant versus non-malignant fibroblasts. Importantly, these evaluations will be performed in physiologically relevant substrates (e.g. collagen:Matrigel gels) that resemble the physical and chemical properties of living tissues and diminish the activation of fibroblasts resulting from in vitro manipulation. As part of an ongoing effort in the lab, this project also aims to establish novel methodologies to assess ER fragments and the inter-cells signalling using these exomes and ER fragments, which may affect cancer cell stemness and therapeutic resistance. To gain further knowledge of their molecular characteristics proteomics data will be used to make bioinformatics models.


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