Project acronym GLIOMA
Project Molecular Mechanisms of Glioma Genesis and Progression
Researcher (PI) Joan Seoane
Host Institution (HI) FUNDACIO PRIVADA INSTITUT D'INVESTIGACIO ONCOLOGICA DE VALL-HEBRON (VHIO)
Country Spain
Call Details Starting Grant (StG), LS6, ERC-2007-StG
Summary Glioma is the most common and aggressive tumour of the brain and its most malignant form, glioblastoma multiforme, is nowadays virtually not curable. Very little is known about glioma genesis and progression at the molecular level and not much progress has been achieved in the treatment of this disease during the last years. The understanding of the molecular mechanisms involved in the biology of glioma is essential for the development of successful and rational therapeutic strategies. Our project aims to: 1- Study the role of the TGF-beta, Shh, Notch, and Wnt signal transduction pathways in glioma. These pathways have been implicated in glioma but still not much is known about their specific mechanisms of action. 2- Study of a cell population within the tumour mass that has stem-cell-like characteristics, the glioma stem cells, and how the four mentioned pathways regulate their biology. 3- Study the role of a transcription factor, FoxG1, that has an important oncogenic role in some gliomas and that it is regulated by the four mentioned pathways interconnecting some of them. Our approach will be based on a tight collaboration with clinical researchers of our hospital and the study of patient-derived tumours. We will analyse human biopsies, generate primary cultures of human tumour cells, isolate the stem-cell-like population of patient-derived gliomas and generate mouse models for glioma based on the orthotopical inoculation of human glioma stem cells in the mouse brain to generate tumours with the same characteristics as the original human tumour. In addition, we will also study genetically modified mouse models and established cell lines. We expect that our results will help understand the biology of glioma and cancer, and we aspire to translate our discoveries to a more clinical ambit identifying molecular markers of diagnosis and prognosis, markers of response to therapies, and unveil new therapeutic targets against this deadly disease.
Summary
Glioma is the most common and aggressive tumour of the brain and its most malignant form, glioblastoma multiforme, is nowadays virtually not curable. Very little is known about glioma genesis and progression at the molecular level and not much progress has been achieved in the treatment of this disease during the last years. The understanding of the molecular mechanisms involved in the biology of glioma is essential for the development of successful and rational therapeutic strategies. Our project aims to: 1- Study the role of the TGF-beta, Shh, Notch, and Wnt signal transduction pathways in glioma. These pathways have been implicated in glioma but still not much is known about their specific mechanisms of action. 2- Study of a cell population within the tumour mass that has stem-cell-like characteristics, the glioma stem cells, and how the four mentioned pathways regulate their biology. 3- Study the role of a transcription factor, FoxG1, that has an important oncogenic role in some gliomas and that it is regulated by the four mentioned pathways interconnecting some of them. Our approach will be based on a tight collaboration with clinical researchers of our hospital and the study of patient-derived tumours. We will analyse human biopsies, generate primary cultures of human tumour cells, isolate the stem-cell-like population of patient-derived gliomas and generate mouse models for glioma based on the orthotopical inoculation of human glioma stem cells in the mouse brain to generate tumours with the same characteristics as the original human tumour. In addition, we will also study genetically modified mouse models and established cell lines. We expect that our results will help understand the biology of glioma and cancer, and we aspire to translate our discoveries to a more clinical ambit identifying molecular markers of diagnosis and prognosis, markers of response to therapies, and unveil new therapeutic targets against this deadly disease.
Max ERC Funding
1 566 000 €
Duration
Start date: 2008-08-01, End date: 2014-07-31
Project acronym RESCARF
Project Renal stem cells: possible role in kidney pathologies and as new theraputic tools
Researcher (PI) Paola Romagnani
Host Institution (HI) UNIVERSITA DEGLI STUDI DI FIRENZE
Country Italy
Call Details Starting Grant (StG), LS6, ERC-2007-StG
Summary Chronic Kidney Disease (CKD) affects 11% of the adult population and is considered by the WHO as one of the health emergencies of the 21st century. Although cell therapy might be beneficial for CKD, human stem cells that might be used to improve kidney function were so far unknown. Recently, we demonstrated the existence of resident stem cells in the urinary pole of the Bowman’s capsule of adult human kidney and therefore named as adult parietal epithelial multipotent progenitors (APEMP). Injection of APEMP in SCID mice affected by acute renal failure, induced regeneration of tubular structures and reduced morphological and functional kidney damage. More recently, we found that APEMP are highly represented in embryonic kidneys and constitute the common progenitor of tubular cells and podocytes. The first aim of this project is to assess the regenerative properties of APEMP in in vivo models of glomerular injury and their potential use as a novel therapeutic tool to prevent the deterioration of kidney function in chronic renal failure. Second, we will try to identify the mechanisms that regulate the growth, survival, differentiation, and migration of APEMP, which is critical to set up cell therapies of renal injury which should be effective and safe. To this end, the role of different molecular pathways such as Sonic hedgehog, Wnt/beta-catenin, Notch, TGF-beta/BMP and of CXCR4, CXCR7 or CXCR3-B chemokine receptors in the regenerative activity of APEMP will be investigated. Third, to assess whether APEMP directly contribute to kidney regeneration after glomerular or tubular damage, transgenic animals in which APEMP are genetically tagged will be generated. Fourth, by using transgenic animals we will try to understand if an alteration of APEMP growth and/or differentiation is implicated in the pathogenesis of some renal disorders that frequently progress towards end stage renal disease.
Summary
Chronic Kidney Disease (CKD) affects 11% of the adult population and is considered by the WHO as one of the health emergencies of the 21st century. Although cell therapy might be beneficial for CKD, human stem cells that might be used to improve kidney function were so far unknown. Recently, we demonstrated the existence of resident stem cells in the urinary pole of the Bowman’s capsule of adult human kidney and therefore named as adult parietal epithelial multipotent progenitors (APEMP). Injection of APEMP in SCID mice affected by acute renal failure, induced regeneration of tubular structures and reduced morphological and functional kidney damage. More recently, we found that APEMP are highly represented in embryonic kidneys and constitute the common progenitor of tubular cells and podocytes. The first aim of this project is to assess the regenerative properties of APEMP in in vivo models of glomerular injury and their potential use as a novel therapeutic tool to prevent the deterioration of kidney function in chronic renal failure. Second, we will try to identify the mechanisms that regulate the growth, survival, differentiation, and migration of APEMP, which is critical to set up cell therapies of renal injury which should be effective and safe. To this end, the role of different molecular pathways such as Sonic hedgehog, Wnt/beta-catenin, Notch, TGF-beta/BMP and of CXCR4, CXCR7 or CXCR3-B chemokine receptors in the regenerative activity of APEMP will be investigated. Third, to assess whether APEMP directly contribute to kidney regeneration after glomerular or tubular damage, transgenic animals in which APEMP are genetically tagged will be generated. Fourth, by using transgenic animals we will try to understand if an alteration of APEMP growth and/or differentiation is implicated in the pathogenesis of some renal disorders that frequently progress towards end stage renal disease.
Max ERC Funding
820 200 €
Duration
Start date: 2008-10-01, End date: 2012-09-30
