The Iris project (InheRited Immune diSorders) is a gene therapy project for inherited monogenic diseases of the immune system. It aims to develop gene therapy products for severe hereditary immune deficiencies and thus, offer a refundable universal cure through our health system. Selected by an international committee of experts, this project is led by Pr. Marina CAVAZZANA, and the coordinating institution is Assistance Publique-Hôpitaux de Paris (AP-HP). This project will be financed with € 9.9 million. The selected consortium includes AP-HP, Imagine Institute, INSERM, Clinical Institute of Mice, and Flash Therapeutics. For more information, please download the IRIS project press release .
The main objective of the EU-funded TheraLymph project is to develop treatment to ameliorate Lymphedema condition using LentiFlash technology in a non-integrative gene therapy approach. The project consortium's translational research programme brings together scientists and physicians from 5 European countries and will be focused on patients who developed lymphedema after breast cancer. The project goal is to validate the best molecule combination for gene therapy and to finalise phase I/II clinical trials at the affiliated hospital. For more information, please visit the Theralymph project website.
University of Helsinky
This project will be carried out in the Biomedicum Helsinki Research Center. It is a unique environment, one of few in Europe where all fields of biomedical research are located on the same campus, in the Academic Medical Center Helsinki (AMCH). The Translational Cancer Biology group, led by Dr. Alitalo, consists of 30 members. The group investigates the induction of lymphatic vessel growth and its benefits in lymphedema, using viral vector transduction, as well as the organ-specific heterogeneity and functions of lymphatic vessels using a combination of state-of-the-art molecular, cellular and genetic in vivo methods. The group also investigates the role of meningeal lymphatic vasculature in neuroinflammation, neurodegenerative diseases. The team further characterises responses of lymphatic vessels to cancer therapies, with a focus on clinically relevant immunotherapy approaches.
University of Lausanne
Vascular and Tumor Biology Laboratory is part of the Department of Oncology of UNIL and is an adjunct member of Lausanne branch of Ludwig Institute for Cancer Research Lausanne, that is specializing in tumor immunology and immune therapy. Our main research interests are in the molecular mechanisms of lymphatic and blood vessel growth and remodeling, and their role in normal organ function and diseases, such as inflammation and cancer.
The key task in the current application will be the analyses of the crosstalk of immune cells and lymphatic vessels in adipose tissue.
University of Uppsala
Vascular Development Laboratory headed by Dr. Mäkinen develops and utilizes genetic mouse models in combination with molecular and cell biological approaches to study mechanisms that regulate the morphogenesis and functional specialisation of the vasculature. The lab also investigates how regulators of developmental (lymph)angiogenesis impact on genetic human diseases such as lymphoedema and vascular malformations.
As part of the proposed research, the key tasks of the team include determining the molecular dentity of collecting lymphatic vessels of the adipose tissue in mice, and developing methods for their visualization in vivo, which lie within the core expertise of the lab.
University of Liège
The Laboratory of Biology of Tumor and Development (LBTD) belongs to the GIGA-Cancer in the GIGAResearch Center (ULg), a major multidisciplinary center of research in life sciences composed of >600 researchers. In this center, the PI’s team members have access to fully equipped and staffed core facilities: GIGA-Imaging, GIGA Mouse Facility and Transgenics, GIGA Proteomics, GIGA Genomics, GIGA-Viral Vectors Platforms. Facilities necessary and available to the project also include biohazard cell culture hood, incubator, XCellIgence, IncuCyte Zoom System, laboratory space equipped for DNA and RNA isolation/analysis and Western immunoblotting.
In the TheraLymph project, Agnès Noel and collaborators will bring an expertise in pathological lymphangiogenesis and original experimental in vivo and in vitro models of (lymph)angiogenesis and lymphoedema. They will also provide access to an expertise in Nuclear magnetic resonance (NMR)-based metabolomics.
De Duve Institute
The Laboratory of Human Molecular Genetics, headed by Prof Miikka Vikkula, MD, PhD, focuses on characterization of the underlying pathophysiology of vascular anomalies, such as lymphedema, as well as cleft lip and palate, and selected cancers. The long-term goal is to develop molecular precision therapies for these disorders. The lab is specialized in evaluating the contribution of genetic variation to human disease. This research is based on blood and tissue samples collected from patients in collaboration with clinicians and multidisciplinary centers worldwide.
The lab analyses patients’ genomes using highthroughput (NGS) sequencing, including targeted panels, WES (whole exome sequencing), WGS (whole genome sequencing) and RNAseq. With its full-time bioinformatician, the group has developed an in-house software called Highlander implementing specialized bioinformatic tools for NGS analyses.
The Laboratory of Pathophysiology of Adipose Tissue presented a number of important contributions in studies focused at changes of metabolic, endocrine and immune characteristics of AT during lifestyle - diet and physical activity- interventions in obese population. The main aim of the present activity is to elucidate a role of lipogenic and adipogenic capacity and inflammatory state of AT in ethiopathogenesis of obesity, type 2 diabetes, lymphedema and in pathogenesis of metabolic disturbances associated with aging. Laboratory is focused on clinical and translational research combining clinical studies with patients and in vitro laboratory techniques to analyze processes that underlie, or mediate disturbances related to dysfunctional adipose tissue.
In TheraLymph, the Laboratory will be dedicated to elucidation of the crosstalk between LEC and adipocytes.
The PI laboratory is located in the Institute of Cardiovascular and Metabolic Diseases (I2MC) created in 2011 by Inserm. The research activity focuses on metabolic, cardiovascular and renal diseases. The main feature of I2MC is the gathering of basic scientists together with clinicians working on metabolic risk factors (obesity, diabetes and dyslipidemia) and their cardiovascular complications (thrombosis, atherosclerosis, cardiac and renal failure).
The laboratory headed by Dr Garmy-Susini studies molecular regulations of (lymph)angiogenic factors in vascular pathologies. It developed research axes in the field of gene expression control in response to stress and in pathophysiology of the lymphatic system, connected to therapeutic axes of gene therapy of ischemic heart disease and lymphedema. The main objectives of the lab are to 1/identify the pathophysiology of the lymphatic system in lymphedema, 2/characterize regulation of lymphangiogenesis-related gene expression in stress conditions (hypoxia, ER stress…), and 3/develop innovative therapies to restore lymphatic flow to improve healing in ischemic heart and in lymphedema.
As scientific coordinator, INSERM will participate to all the basic science work packages. They will provide tools for each partner and they will coordinate the scientific project.
The project will be performed at the “Institute for Research on Cancer and aging of Nice (IRCAN). The team of Gilles Pagès focused its research on the regulation of angiogenic factors and their role as markers of sensitivity or resistance to treatments in different cancers. The first major paper of the team was published in Blood in 2004 for the efficacy of Gleevec in chronic myeloid leukemia; (Legros, L et al). More recently the team has focused on renal cell carcinoma and has published pivotal papers on the mechanisms of resistance to anti-angiogenic drugs. We also published a pivotal paper for the comparison of radiotherapy photons or protons and their relative efficacy for the treatment of head and neck carcinoma.
IRCAN will be responsible of the work package “Risk factor associated with lymphedema: chemotherapy and radiotherapy”.