Partner 1: Foundation of Research and Technology Hellas, Greece
Dr Aristides Eliopoulos is associate senior researcher in IMBB-FORTH and chief co-ordinator of the INFLA-CARE programme. Work in his lab is focused on studies of inflammation-driven cancer in pre-clinical models, particularly in terms of the role played by the Tpl2 kinase both in inflammatory response and in cancer cells.
Partner 2: Austrian Academy of Sciences, Austria
Josef Penninger is Scientific Director of the Institute for Molecular Biotechnology, Vienna, whose research interests include disease pathogenesis of immunology, cancer and cardiovascular disease. As a member of the INFLA-CARE programme his lab will be investigating inflammation-driven cancer in terms of the roles played by the MMK7 kinase both in the inflammatory response and in cancer cells.
Partner 3: Ben Gurion University, Israel
Ron N. Apte, PhD is a Professor of Immunology and together with senior scientist Elena Voronov, MD/PhD work in this lab is centred on mouse models of inflammation-associated cancer and evaluation of the role of IL-1 in tumor-host interactions. The team has significant experience in mechanisms of carcinogenesis, tumor invasiveness and angiogenesis.
Partner 4: Biomedical Sciences Research Centre “Alexander Flemming”, Greece
Dr. George Kollias is the President and Scientific Director of the Biomedical Sciences Research Center "Alexander Fleming" and Director of its Institute of Immunology. Dr. Kollias' lab has expertise in transgenic, gene mutational and knockout technology, molecular and cellular biology and immunology. The research interests of the lab include cytokines in inflammation and autoimmunity and the lab is best known for transgenic and knockout research in the field of TNF function in pathophysiology.
Dr Dimitris L. Kontoyannis and his group at the Institute of Immunology of the BSRC are involved in work which focuses on a selective set of post-transcriptional modifiers, called “ARE-binding proteins” and their functions in mRNA utilization during inflammatory responses and cancer. The lab studies RNA-binding proteins in vivo using conditional transgenesis, pre-clinical models of inflammation and epithelial cancer, gene expression assays and systems for RNA:protein interactions.
Research in the laboratory of Dr George Panayotou focuses on signaling pathways that are activated by mitogenic stimuli, pro-inflammatory cytokines and a variety of environmental stresses. The lab has a particular interest in the role of dual-specificity phosphatases (DUSP) in the MAP kinase pathway, with emphasis on JNK-specific enzymes, studied at the biochemical level. The lab is also involved in the proteomic analysis of tumorigenic transformation, using several model cell line systems.
Partner 5: Genoa G.Gaslini Childrens’ Hospital, Italy
The Principal Investigator Dr Mirco Ponzoni is Head of the Experimental Therapy Unit at the Oncology Department and at the Research Department of the Gaslini’s Institute of Genoa, Italy. Mirco and other members of his group have a very wide spectrum of technical expertise in nanotechnology, in live cell imaging, cell and molecular biology, cancer biochemistry and novel experimental therapies for neuroectodermal tumors.
Partner 6: Univerzita Palackeho Olomouci, Czech Republic
Dr Jiri Bartek is the Head of the Genome Integrity Laboratory and Professor at the Molecular Pathology Department, Medical Faculty of the Palacky University of Olomouc, Czech Republic. His lab specializes in cell and molecular biology, fluorescence imaging as well as siRNA-based loss-of-function screens and cancer genetics and pathology. Specifically this lab is involved in analysis of DNA damage response pathways in inflammation-associated cancer and functional shRNA-based screening for the identification of novel NEMO/IKK regulators.
Partner 7: Institut Gustave Roussy, France
The research group of Dr Laurence Zitvogel is studying the effects of inflammation on the immune system. Specifically, the lab is working to understand how cancer treatment itself could lead to inflammation, which in turn activates immune cells, leading to therapeutic effects and patient cure. The group uses preclinical models to identify and shape novel anti-cancer therapies.
Partner 8: University of Oxford, U.K.Prof. Fiona Powrie
is a Wellcome Trust Senior Research Fellow at the Sir William Dunn School of Pathology. The major focus of work in her lab is mucosal immune regulation and the breakdown in regulatory mechanisms can precipitate human inflammatory bowel disease (IBD). Her research for INFLA-CARE will use preclinical models of intestinal inflammation-associated colon cancer to evaluate of the role of cytokines in chronic intestinal inflammation and cancer. Additionally, the lab will also work to define the genetic susceptibility to inflammation-associated colon cancer in disease models.Partner 9: Research Centre Borstel, Germany
Dr Silvia Bulfone-Paus
and her group have been studying the role of interleukin messengers such as IL-15 in the regulation of inflammatory processes in preclinical models of allergy, tumor and infectious diseases. They have previously shown that IL-15 can act as a pleiotropic cytokine, modulating the immune system and also acting as a potent inhibitor of apoptosis.
Partner 10: Spanish National Cancer Centre, Spain
Research in the lab of Dr Angel Nebreda
is focused on understanding basic mechanisms of cell proliferation and differentiation, in particular how external signals are interpreted by cells to elaborate the appropriate responses. Specifically, their work includes investigation of the mechanisms of signal transduction by the stress-activated kinases p38α and p38β and their role in carcinogenesis. The lab is also involved in the analysis of the regulation and role of the RINGO/Speedy proteins, a new family of CDK activators.
Partner 11: National and Kapodistrian University of Athens, GreeceVassilis Gorgoulis
is associate professor of Pathology at the University of Athens. His group is involved in the analysis of human clinical specimens, particularly in terms of protein markers and posttranslational modifications involved in regulation of DNA damage response, apoptosis genomic instability and senescence. Research in his lab will also involve the evaluation of immunohistochemical and in situ hybridisation analyses of disease tissue performed by INFLA-CARE partners.
Partner 12: University of Birmingham, UK
Jorge Caamaño, is a Senior Lecturer at the MRC Centre for Immune Regulation, School of Immunity and Infection of the College of Medicine, University of Birmingham, UK. His team has extensive expertise in the use of preclinical models to study the function of the NF-kB transcription factors in particular the alternative activation pathway, and their target genes mediating the cell-cell interactions involved in the formation of secondary lymphoid tissues and inflammatory diseases. Specifically, this lab will be working with knock-out and transgenic preclinical models to study the involvement of the NF-kB transcription factors in colitis-associated colon cancer. The research will also include experiments with cell culture models and re-aggregate organ cultures to assess NF-kB function and its target genes during the initiation and maintenance of inflammation.
Partner 13: University of Cologne, Germany
The group of Dr Manolis Pasparakis focuses on the role of inflammation in disease pathogenesis. Using ‘state of the art’ conditional mutagenesis approaches their research studies in vivo the function of intracellular signalling cascades activated downstream of cytokine and innate immune receptors, including the NF-kB and MAP kinase signalling pathways. By combining conditional mutagenesis with preclinical models of human disease, their aim is to understand the function of genes regulating NF-kB and MAP kinase signalling in the pathogenesis of inflammatory diseases and cancer.
Partner 14: University of Bristol, U.K.
Dr Neil Perkins runs a group focusing on NF-κB, a collective name for the complexes formed by the multigene NF-κB-Rel family which function as DNA-binding proteins and transcription factors. The pathways regulating NF-κB are considered to be good targets for the development of new anti-inflammatory and anti-cancer drugs and research in this laboratory is focused on how NF-κB subunits are regulated by oncogenes, tumour suppressors and stimuli associated with cancer development and therapy. As it is thought that NF-κB can function as a tumour suppressor as well as a tumour promoter, the Bristol group is investigating mechanisms regulating the cellular pathways which lead to these responses. Additionally, as NF-κB is activated by many cancer therapies and can have an inhibitory effect on treatment, research is ongoing into the implications of these results for both traditional and NF-κB based cancer therapy.Partner 15: Univerity of Newcastle, UK
Work in the laboratories of Dr Derek Mann
, Newcastle University is focused on the so-called Hepatic Inflammation-Fibrosis-Cancer (HIFC) axis which is a common pathobiological continuum observed in chronic liver disease caused by a variety of injuries (alcohol, metabolic, viral, autommune and genetic). A major interest of the lab is NF-kB; cell-specific regulation of NF-kB has been investigated in hepatic myofibroblasts which are the pivotal cellular controllers of fibrosis. The role of myofibroblasts in development and progression of hepatocellular carcinoma will be investigated as part of INFLA-CARE using a novel single chain antibody targeting technology that enables depletion of myofibroblasts.
Partner 16: Department of Molecular Medicine and Biotechnology, School of Medicine, University of Rijeka, Croatia
Siniša Volarević and his team have been studying the consequences of ribosomal protein deficiencies in pre-clinical models for several years. Initially, research from the lab demonstrated that inducible deletion of the Rps6 gene in liver inhibits the synthesis of the 40S ribosomal subunit as well as proliferation of liver cells following partial hepatectomy, despite seemingly unaffected protein synthesis. These observations suggested the existence of a novel checkpoint, downstream of the deficiency in ribosome biogenesis. More recent studies from the lab provided convincing evidence for the existence of this checkpoint and demonstrated that the p53 tumor suppressor is its critical component. The group continues to investigate the molecular basis of this checkpoint response and determine its role in pathogenesis of various diseases. As part of INFLA-CARE, they are involved in studies to understand the role of ribosome biogenesis and ribosome checkpoint in malignant transformation and tumor progression associated with chronic inflammatory imbalance.
Partner 17: University of Vienna, Austria
The laboratory of Manuela Baccarini focuses on deciphering signaling pathways in vivo. The Raf/MEK/ERK signaling cascade is a highly conserved signal transduction module whose activation results in a number of different physiological outcomes. Depending on the cell type or the stimulus used, the pathway has been implicated in proliferation, differentiation, apoptosis, and migration. Because of this wide range of activities, these kinases are considered attractive (anticancer) therapeutic targets. However, their essential functions in the context of the whole organism are still incompletely known. The Baccarini laboratory is using conditional mutagenesis to define the essential function(s) of Raf-1, B-Raf and Mek-1 in models of organ development, remodeling, and neoplasia.
Partner 18: Weizmann Institute of Science, Israel
Work in the lab of Dr Moshe Oren focuses on the biology and biochemistry of the p53 tumor suppressor and its associated regulatory network. In particular, the lab is studying the regulation of p53 levels and activity in response to various types of stress, the factors that determine the ability of p53 as a transcription factor to modulate the expression of different subsets of genes in response to different types of signals, and the rules that dictate the interaction between p53 and chromatin. The lab is also studying Mdm2, an E3 ubiquitin ligase that serves as the main negative regulator of p53, as well as proteins that interact with Mdm2 and either regulate its activity towards p53 or serve as alternative substrates for its E3 activity; one such protein is the Lats2 tumor suppressor, whose roles in the p53 network are being investigated in the lab.
Also at the Weizmann Institute of Science, the laboratory of Varda Rotter is studying p53, with a special focus on the role of mutant p53 in the development and the progression of tumor growth. In recent years the Rotter team established an in vitro transformation model whereby primary immortalized cells are induced to transform in a well-defined stepwise process into cancer cells. By using a genome wide profile analysis of this system several gene signatures that are specific for defined steps of the in vitro transformation process were identified. It is expected that unraveling the gene networks mediated by these gene signatures may provide new insights to permit the development of p53-based therapy.
Partner 19: Almac Diagnostics, UKAlmac Diagnostics
develops and provides a range of genomics solutions for the advancement of science and the improvement of patient care. The company has secured a prime position in the rapidly advancing field of genomic technology, being the first Affymetrix Service Provider in the world to gain ISO 17025 accreditation for Gene Expression
services. In addition, Almac Diagnostics has also established itself as a leader in scientific innovation: its unique range of Disease Specific Arrays (DSA™) research tools
(patent pending) are the first microarrays available which are based on the transcriptome of an individual disease. In the context of INFLA-CARE, Almac will assist with the detailed experimental design, performance and data analysis of microarrays aiming to define changes in the transcriptome during inflammation-driven cancer. The company will also generate a liver cancer DSA designed to work with both fresh frozen and paraffin embedded tissue
, enabling retrospective analysis.Partner 20: Biomedcode, GreeceBiomedcode
provides preclinical evaluation of drugs in unique, spontaneous transgenic models of autoimmune and inflammatory diseases. The company also offers services in histopathology, pharmacogenomics and immunogenicity protocols. Biomedcode has an active R&D base aimed at generating novel transgenic models of disease. Its role in INFLACARE is to histologically evaluate models of inflammation driven cancer and to preclinically test humanised TNF transgenic models for therapeutic benefits.Partner 21: Helios Biosciences, France
The company provides services consisting of tissue and cellular gene expression analysis. To put together the power of high-throughput genomics-based data, HELIOS
has developed an in silico
modelling platform dedicated to the selection of therapeutic targets. This platform is used for dynamic modeling leading to a hierarchical classification of the targets, according to the proximity between the final state of the pathway obtained by simulating their change of activity, and a healthy state of the pathway. This capability makes a substantial impact on strategies for characterising therapeutic targets in complex diseases.