Cancer Stem Cells and Fibroinflammatory Microenvironment

In the Cancer Stem Cells and Fibroinflammatory Microenvironment Group, we study CSCs in the context of pancreatic ductal adenocarcinoma (PDAC), the 4th leading cause of cancer related deaths in developed countries. We are running a combined basic and translational research program, which synergistically combines studies on the biology of mouse and human CSCs, including their in vivo fibroinflammatory microenvironment, in order to enhance our understanding of the regulatory machinery of CSCs. Specifically, the avenues of research that the group is pursuing are: 

1) The establishment of one of the largest Biobanks in Spain of Patient-derived PDAC xenografts for in vivo pre-clinical stuides and CSC-specific analyses.

2) The identification and characterization of new biomarkers for the detection of CSCs from different solid tumors. We have discovered several new biomarkers present on the cell surface or within CSCs, across several solid tumors. For example, the CSC biomarker termed Autofluorescence, is the result of riboflavin accumulation in ABCG2-coated intracellular vesicles exclusively found in CSCs. We are currently using autofluorescence as a means of isolating CSCs for in depth biological and molecular characterization studies. 

3) The identification of proteins that govern key CSC phenotypes, such as “stemness”, epithelial to mesenchymal transition (EMT), oxidative phosphorylation (i.e. mitochondrial respiration) and chemoresistance. For example, we have discovered that the Interferon Stimulated Gene 15 (ISG15) is not only up-regulated in CSCs, but its function as a Ubiquitin-like modifier is necessary for many CSCs biological processes.

4) Comprehensively understand the cellular make-up of the CSC niche and the larger more complex tumor microenvironment, specifically the role of tumor-associated macrophages (TAMs) in "activating" CSCs, with respect to the different environmental proteins they can secrete in response to cues from the tumor and how these proteins alter the function of the CSCs at the level of EMT and chemoresistance.

Our Research Projects, divided into 4 main areas, are detailed below. 


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Metabolic and Immune Diseases

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Neurological Diseases and Aging

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Rare Diseases

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