Fondation MEDIC

www.fondation-medic.ch

Research groups

 

Determinants of response to therapy

Melanogenesis in melanoma progression and therapy [updated: 13.09.2015]
Project leader: Ghanem Ghanem
The Ghanem laboratory studies the biology of melanoma, with the intention to identitfy markers which are prognostic (distinguish melanoma with low risk of progression from high risk melanomas) and new therapies for melanoma. A promising new marker is TYRP1, of which the biology is studied in melanoma cell lines. A promising new therapy for melanoma could be Dasatinib. The mechanisms of action of this drug are explored, in order to allow identification of patients which might benefit from Dasatinib treatment.
Melanogenesis in melanoma progression and therapy [updated: 13.09.2015]
Project leader: Ghanem Ghanem
The Ghanem laboratory studies the biology of melanoma, with the intention to identitfy markers which are prognostic (distinguish melanoma with low risk of progression from high risk melanomas) and new therapies for melanoma. A promising new marker is TYRP1, of which the biology is studied in melanoma cell lines. A promising new therapy for melanoma could be Dasatinib. The mechanisms of action of this drug are explored, in order to allow identification of patients which might benefit from Dasatinib treatment.
Characterization of molecular biomarkers relevant to the biology, diagnosis and prognosis of peripheral T-cell lymphomas [updated: 13.09.2015]
Project leader: Laurence de Leval
In the last decade there has been strong emphasis in cancer research on the elucidation of molecular mechanisms of oncogenesis. This followed the discovery that cancer is a disease of genes, in view of the fact that abnormalities in genes or their expression constitute essential hallmarks of malignant growth. The DeLeval group intends to gain new insight into the molecular mechanisms involved in a specific type of malignant lymphomas, the peripheral T/NK cell lymphomas. Subgroups have been identified in this group of rare malignancies, which differ in behavior. Elucidation of the molecular mechanisms involved might have important implications for diagnosis, clarifying boundaries and opening rational approaches towards therapy choice. This is done through molecular annotation of large case series (internationally collected) with detailed follow-up and intense bioinformatics efforts to unravel gene expression patterns, how these correlate to behavior and with response to therapy.
Characterization of molecular biomarkers relevant to the biology, diagnosis and prognosis of peripheral T-cell lymphomas [updated: 13.09.2015]
Project leader: Laurence de Leval
In the last decade there has been strong emphasis in cancer research on the elucidation of molecular mechanisms of oncogenesis. This followed the discovery that cancer is a disease of genes, in view of the fact that abnormalities in genes or their expression constitute essential hallmarks of malignant growth. The DeLeval group intends to gain new insight into the molecular mechanisms involved in a specific type of malignant lymphomas, the peripheral T/NK cell lymphomas. Subgroups have been identified in this group of rare malignancies, which differ in behavior. Elucidation of the molecular mechanisms involved might have important implications for diagnosis, clarifying boundaries and opening rational approaches towards therapy choice. This is done through molecular annotation of large case series (internationally collected) with detailed follow-up and intense bioinformatics efforts to unravel gene expression patterns, how these correlate to behavior and with response to therapy.
Epigenetic mechanisms in the development of pediatric tumors [updated: 10.11.2016]
Project leader: Nicolò Riggi
Whereas the development of adult tumors frequently rely on the stepwise accumulation of genetic alterations, pediatric tumors are almost invariably initiated by a very limited number of genetic events, frequently in the form of single balanced chromosomal translocations. Pediatric tumors, therefore, are driven by specific and unique oncogenic events, leading to a massive deregulation of cellular differentiation, proliferation, and ultimately malignant transformation. The Riggi laboratory is particularly interested in understanding the initial deregulation of epigenetic transcriptional programs allowing the transformation of permissive cell of origin, and the subsequent development of intratumoral heterogeneity.
Epigenetic mechanisms in the development of pediatric tumors [updated: 10.11.2016]
Project leader: Nicolò Riggi
Whereas the development of adult tumors frequently rely on the stepwise accumulation of genetic alterations, pediatric tumors are almost invariably initiated by a very limited number of genetic events, frequently in the form of single balanced chromosomal translocations. Pediatric tumors, therefore, are driven by specific and unique oncogenic events, leading to a massive deregulation of cellular differentiation, proliferation, and ultimately malignant transformation. The Riggi laboratory is particularly interested in understanding the initial deregulation of epigenetic transcriptional programs allowing the transformation of permissive cell of origin, and the subsequent development of intratumoral heterogeneity.
Mechanisms that govern energy regulation in cancer stem cells (CSC) [updated: 20.10.2016]
Project leader: Ivan Stamenkovic
Cancer cells are very different from normal cells in the way they handle their energy supply. Malignant cells rely on both oxidative phosphorylation and glycolysis to generate sufficient energy for their metabolic requirements: rapidly-growing tumor cells typically have glycolytic rates that are up to 200 times higher than those of normal cells, even when abundant oxygen is present (known as the Warburg effect). How energy supply is handled by cancer stem cells (CSC) is completely unknown. This is relevant as according to current concepts CSC the cell population that drives progression and is responsible for therapy failure. Given that CSC grow slowly, glycolysis may not be as critical as in more rapidly proliferating cells. The Stamenkovic group studies energy provision in CSC, using glioblastoma and Ewing sarcoma as models.
Mechanisms that govern energy regulation in cancer stem cells (CSC) [updated: 20.10.2016]
Project leader: Ivan Stamenkovic
Cancer cells are very different from normal cells in the way they handle their energy supply. Malignant cells rely on both oxidative phosphorylation and glycolysis to generate sufficient energy for their metabolic requirements: rapidly-growing tumor cells typically have glycolytic rates that are up to 200 times higher than those of normal cells, even when abundant oxygen is present (known as the Warburg effect). How energy supply is handled by cancer stem cells (CSC) is completely unknown. This is relevant as according to current concepts CSC the cell population that drives progression and is responsible for therapy failure. Given that CSC grow slowly, glycolysis may not be as critical as in more rapidly proliferating cells. The Stamenkovic group studies energy provision in CSC, using glioblastoma and Ewing sarcoma as models.

Immune response to cancer

Reprogramming Tie-2 expressing monocytes in breast cancer to promote protective anti-tumor immune responses [updated: 19.10.2016]
Project leader: Marie-Agnès Doucey
In all cancers, the host (the body of the patient) provides important tissue components to sustain the growth of tumour cells. When the tumour is still small this will be primarily oxygen and nutrients. When the mass of tumor cells grows bigger, full tissue architecture will develop, including the outgrowth of blood vessels, to support the developing tumour. The growth of blood vessels is called angiogenesis and this process has been an intense area of research, leading to new anticancer drugs. Still, the process is still incompletely. The Doucey group studies the role of a particular population of cells in the circulation, the Tie2 positive monocytes, in the process of angiogenesis in breast cancer.
Reprogramming Tie-2 expressing monocytes in breast cancer to promote protective anti-tumor immune responses [updated: 19.10.2016]
Project leader: Marie-Agnès Doucey
In all cancers, the host (the body of the patient) provides important tissue components to sustain the growth of tumour cells. When the tumour is still small this will be primarily oxygen and nutrients. When the mass of tumor cells grows bigger, full tissue architecture will develop, including the outgrowth of blood vessels, to support the developing tumour. The growth of blood vessels is called angiogenesis and this process has been an intense area of research, leading to new anticancer drugs. Still, the process is still incompletely. The Doucey group studies the role of a particular population of cells in the circulation, the Tie2 positive monocytes, in the process of angiogenesis in breast cancer.
Exploring the immune infiltrate in human breast cancer [updated: 24.10.2016]
Project leader: Karen Willard-Gallo
The Molecular Immunology Laboratory at the Institut Jules Bordet focuses on both fundamental and translational research related to understanding normal lymphocyte functions and how they deviate in human cancer. Current basic research projects examine how specific T and B cell subpopulations work together in tumor-associated tertiary lymphoid structures to elicit durable anti-tumor immune responses. Current translational research projects are focused on establishing an immunological grade for breast cancer that is based on the extent and organization of the lymphocytic infiltrate. Scoring the extent of tumor infiltration by lymphocytes and the frequency of their organization in tertiary lymphoid structures is being investigated as a clinicopathological parameter to stratify patients for treatment options.
Exploring the immune infiltrate in human breast cancer [updated: 24.10.2016]
Project leader: Karen Willard-Gallo
The Molecular Immunology Laboratory at the Institut Jules Bordet focuses on both fundamental and translational research related to understanding normal lymphocyte functions and how they deviate in human cancer. Current basic research projects examine how specific T and B cell subpopulations work together in tumor-associated tertiary lymphoid structures to elicit durable anti-tumor immune responses. Current translational research projects are focused on establishing an immunological grade for breast cancer that is based on the extent and organization of the lymphocytic infiltrate. Scoring the extent of tumor infiltration by lymphocytes and the frequency of their organization in tertiary lymphoid structures is being investigated as a clinicopathological parameter to stratify patients for treatment options.
KillerCD4 T cells: a novel candidate for human tumor immunotherapy [updated: 24.10.2016]
Project leader: Camilla Jandus
The proposed project plans to consolidate and expand the knowledge on human CD4 T cell biology by performing in-depth characterization of a thus far neglected subset of CD4 T cells: the so-called CD4 T killer cells. These cells are emerging as critical mediators in both natural and treatment induced anti-tumor responses. We intend to study key factors influencing their induction, differentiation and plasticity as well as specific markers defining their phenotypic profile. We will also address mechanisms by which they impact anti-tumor immune responses.
KillerCD4 T cells: a novel candidate for human tumor immunotherapy [updated: 24.10.2016]
Project leader: Camilla Jandus
The proposed project plans to consolidate and expand the knowledge on human CD4 T cell biology by performing in-depth characterization of a thus far neglected subset of CD4 T cells: the so-called CD4 T killer cells. These cells are emerging as critical mediators in both natural and treatment induced anti-tumor responses. We intend to study key factors influencing their induction, differentiation and plasticity as well as specific markers defining their phenotypic profile. We will also address mechanisms by which they impact anti-tumor immune responses.
Harnessing T cells for cancer immunotherapy: Modulation of the mTOR signaling pathway to fine tune CD8+ T cell differentiation [updated: 19.10.2016]
Project leader: Pedro Romero
The Romero laboratory studies mechanisms deployed by the immune system to attack cancer cells. The ultimate goal is to develop effective immunotherapies. In this project regulation of the function of a specific set of immune-competent cells (CD8+ T-cells) is examined. It was found that their function is at least in part regulated through micro-RNA, a new species of RNA with important general gene regulatory functions and potentially important as diagnostic tool as well as target for new therapies. The group focuses on melanoma, cancer of pigment forming cells of the skin.
Harnessing T cells for cancer immunotherapy: Modulation of the mTOR signaling pathway to fine tune CD8+ T cell differentiation [updated: 19.10.2016]
Project leader: Pedro Romero
The Romero laboratory studies mechanisms deployed by the immune system to attack cancer cells. The ultimate goal is to develop effective immunotherapies. In this project regulation of the function of a specific set of immune-competent cells (CD8+ T-cells) is examined. It was found that their function is at least in part regulated through micro-RNA, a new species of RNA with important general gene regulatory functions and potentially important as diagnostic tool as well as target for new therapies. The group focuses on melanoma, cancer of pigment forming cells of the skin.
Identifying high-avidity and high-quality individual T-cells in cancer patients [updated: 24.10.2016]
Project leader: Nathalie Rufer
The Rufer lab studies T-cell responses against tumor antigens in cancer patients following therapeutic vaccination and naturally occurring immune responses, with the major goals to improve T-cell based therapy in the fight against cancer. In this project, using a novel developed technology we will isolate the rare tumor-reactive T cells of highest avidity from melanoma patients, which supposedly represent a major correlate of protection against disease. We will further examine the relationship between T-cell receptor avidity and function to identify the most efficient anti-cancer T cells and advance our knowledge of T-cell mediated protection from human diseases.
Identifying high-avidity and high-quality individual T-cells in cancer patients [updated: 24.10.2016]
Project leader: Nathalie Rufer
The Rufer lab studies T-cell responses against tumor antigens in cancer patients following therapeutic vaccination and naturally occurring immune responses, with the major goals to improve T-cell based therapy in the fight against cancer. In this project, using a novel developed technology we will isolate the rare tumor-reactive T cells of highest avidity from melanoma patients, which supposedly represent a major correlate of protection against disease. We will further examine the relationship between T-cell receptor avidity and function to identify the most efficient anti-cancer T cells and advance our knowledge of T-cell mediated protection from human diseases.
The impact of glioblastoma adaptation to hypoxia on anti-tumour immunity [updated: 13.09.2015]
Project leader: Paul R Walker
In this project low oxygen tension, a key characteristic of the brain tumour microenvironment, will be studied in terms of its impact on the dialogue between brain tumour cells and the immune system. Initially studies will concentrate on tumour cell response to low oxygen tension and will identify changes that impact on immune cells. In a later stage of the project, cellular interactions between tumour cells and immune cells will be directly studied, which will allow assessment of the global consequences of hypoxia tumour microenvironment.
The impact of glioblastoma adaptation to hypoxia on anti-tumour immunity [updated: 13.09.2015]
Project leader: Paul R Walker
In this project low oxygen tension, a key characteristic of the brain tumour microenvironment, will be studied in terms of its impact on the dialogue between brain tumour cells and the immune system. Initially studies will concentrate on tumour cell response to low oxygen tension and will identify changes that impact on immune cells. In a later stage of the project, cellular interactions between tumour cells and immune cells will be directly studied, which will allow assessment of the global consequences of hypoxia tumour microenvironment.

Pathobiology of breast cancer

Molecular and pharmacological investigation of the factors contributing to tamoxifen resistance of ERα-positive breast cancers [updated: 06.08.2013]
Project leader: Didier Picard
Estrogen receptor (ER) plays an important role in breast cancer, both in terms of cancer biology and as predictor of response to therapy: ER positive tumours are likely to respond to anti-estrogen drugs (notably tamoxifen). Estrogen receptor positive breast cancers tend to develop resistance for tamoxifen, however. The Picard laboratory studies the molecular biology of the estrogen receptor against this background. Mechanisms of resistance are explored as well as possibilities to overcome this resistance.
Molecular and pharmacological investigation of the factors contributing to tamoxifen resistance of ERα-positive breast cancers [updated: 06.08.2013]
Project leader: Didier Picard
Estrogen receptor (ER) plays an important role in breast cancer, both in terms of cancer biology and as predictor of response to therapy: ER positive tumours are likely to respond to anti-estrogen drugs (notably tamoxifen). Estrogen receptor positive breast cancers tend to develop resistance for tamoxifen, however. The Picard laboratory studies the molecular biology of the estrogen receptor against this background. Mechanisms of resistance are explored as well as possibilities to overcome this resistance.
Unraveling mechanisms of breast cancer dormancy [updated: 19.10.2016]
Project leader: Curzio Ruegg
Cells in normal tissues, like the skin of the intestine, are subjected to well defined stimuli originating from other surrounding microenvironment that influence and control their growth, survival and differentiation. During tumor development and progression, malignant cells modify this microenvironment, for example by attracting blood and lymphatic vessels, fibroblast and inflammatory cells. In return the tumor-modified microenvironment facilitates local tumor progression and distant metastasis formation. Microenvironmental modifications may start early during tumor progression or even precede cancer formation. Collectively, tumor microenvironmental events contribute to determine the outcome of tumor progression: tumor growth, dormancy or metastasis and resistance to therapy. This is what the Ruegg laboratory studies.
Unraveling mechanisms of breast cancer dormancy [updated: 19.10.2016]
Project leader: Curzio Ruegg
Cells in normal tissues, like the skin of the intestine, are subjected to well defined stimuli originating from other surrounding microenvironment that influence and control their growth, survival and differentiation. During tumor development and progression, malignant cells modify this microenvironment, for example by attracting blood and lymphatic vessels, fibroblast and inflammatory cells. In return the tumor-modified microenvironment facilitates local tumor progression and distant metastasis formation. Microenvironmental modifications may start early during tumor progression or even precede cancer formation. Collectively, tumor microenvironmental events contribute to determine the outcome of tumor progression: tumor growth, dormancy or metastasis and resistance to therapy. This is what the Ruegg laboratory studies.
Interrogating breast cancer heterogeneity using next generation sequencing [updated: 22.10.2016]
Project leader: Christos Sotiriou
In order to get a better picture of breast cancer biology, in this project it was decided that 1) the tumor microenvironment and 2) the disseminated and circulating tumor epithelial cells needed to be more carefully studied. The tumor microenvironment consists of elements that are contributed to the tumor by the host (including vessels, mesenchymal stromal cells and inflammatory cells) and signalling molecules which play a role in the communication between cancer cells and the host response. Circulating tumor cells have been found to constitute an integral part of the biology of cancer. Their significance is insufficiently clear, although at least a fraction of these circulating cells must be responsible for cancer metastasis.
Interrogating breast cancer heterogeneity using next generation sequencing [updated: 22.10.2016]
Project leader: Christos Sotiriou
In order to get a better picture of breast cancer biology, in this project it was decided that 1) the tumor microenvironment and 2) the disseminated and circulating tumor epithelial cells needed to be more carefully studied. The tumor microenvironment consists of elements that are contributed to the tumor by the host (including vessels, mesenchymal stromal cells and inflammatory cells) and signalling molecules which play a role in the communication between cancer cells and the host response. Circulating tumor cells have been found to constitute an integral part of the biology of cancer. Their significance is insufficiently clear, although at least a fraction of these circulating cells must be responsible for cancer metastasis.

Pathobiology of colon cancer

Linking tumor heterogeneity with clinically useful subtypes of colon cancer [updated: 19.10.2016]
Project leader: Mauro Delorenzi
In this project the molecular heterogeneity of colorectal cancer is studied in a large series of cases, with detailed clinical follow-up. The basic question asked in this project is why some colorectal carcinomas do not recur after initial treatment but others recur, metastasize and finally kill the patient. Better understanding of this heterogeneity in molecular terms could lead to new diagnostic tools (determining who needs further treatment after initial surgery) and the development of new drugs effective in colorectal cancer.
Linking tumor heterogeneity with clinically useful subtypes of colon cancer [updated: 19.10.2016]
Project leader: Mauro Delorenzi
In this project the molecular heterogeneity of colorectal cancer is studied in a large series of cases, with detailed clinical follow-up. The basic question asked in this project is why some colorectal carcinomas do not recur after initial treatment but others recur, metastasize and finally kill the patient. Better understanding of this heterogeneity in molecular terms could lead to new diagnostic tools (determining who needs further treatment after initial surgery) and the development of new drugs effective in colorectal cancer.
Mechanisms of resistance to anti-angiogenic therapy in colorectal cancer [updated: 19.10.2016]
Project leader: Tatiana Petrova
In this project one particular molecular mechanism in colorectal cancer is studied. This consists of PROX1, a molecule that has been shown to be involved in intestinal adenoma development in mouse models. The experiments conducted have shown that PROX1 is involved in the interaction between the cancer cells and the host stromal cells. Furthermore, PROX1 is closely associated with the signaling pathway involved in regulation of cell differentiation in intestinal mucosa (the Wnt pathway) and also in transformation of intestinal epithelial cells into cancer cells. Present data suggest that PROX1 is involved in progression to later stages (e.g.metastasis) rather than in the initial stages of colorectal cancer development.
Mechanisms of resistance to anti-angiogenic therapy in colorectal cancer [updated: 19.10.2016]
Project leader: Tatiana Petrova
In this project one particular molecular mechanism in colorectal cancer is studied. This consists of PROX1, a molecule that has been shown to be involved in intestinal adenoma development in mouse models. The experiments conducted have shown that PROX1 is involved in the interaction between the cancer cells and the host stromal cells. Furthermore, PROX1 is closely associated with the signaling pathway involved in regulation of cell differentiation in intestinal mucosa (the Wnt pathway) and also in transformation of intestinal epithelial cells into cancer cells. Present data suggest that PROX1 is involved in progression to later stages (e.g.metastasis) rather than in the initial stages of colorectal cancer development.
Comprehensive molecular characterization of colorectal liver metastases: a step towards personalized medicine in stage IV colon cancer [updated: 13.09.2015]
Project leader: Arnaud Roth
In this project gene expression and digital morphology will be used to compare primary colorectal carcinomas with their liver. This project is part of a large international collaborative effort to map in detail morphological and molecular characteristics of primary and metastatic colorectal cancer in order to gain knowledge of the molecular events responsible for tumor progression. One of the questions under study is whether the recently identified consensus molecular subtypes have any relationship with tumor progression and response of metastatic tumors to therapy. Morphology provides spatial resolution, allowing to distinguish between molecular events in cancer cells relative to the stroma and inflammatory/immune response.
Comprehensive molecular characterization of colorectal liver metastases: a step towards personalized medicine in stage IV colon cancer [updated: 13.09.2015]
Project leader: Arnaud Roth
In this project gene expression and digital morphology will be used to compare primary colorectal carcinomas with their liver. This project is part of a large international collaborative effort to map in detail morphological and molecular characteristics of primary and metastatic colorectal cancer in order to gain knowledge of the molecular events responsible for tumor progression. One of the questions under study is whether the recently identified consensus molecular subtypes have any relationship with tumor progression and response of metastatic tumors to therapy. Morphology provides spatial resolution, allowing to distinguish between molecular events in cancer cells relative to the stroma and inflammatory/immune response.