FNR CORE funding - three LIH research projects will tackle disease mechanism and treatment

2018 - 12 - 19

The Luxembourg National Research Fund  (FNR) finances multi-annual thematic research programs with its central funding instrument CORE. Three projects submitted by LIH received the valuable third-party funding for projects that shall start in 2019.

Zoom on the three successful applications:

FNR ATTRACT fellow Prof Dirk Brenner, leading the “Experimental & Molecular Immunology” research group at LIH’s Department of Infection and Immunity, is one of the successful applicants*. He and his team will focus on multiple sclerosis, a neurodegenerative autoimmune disease for which current treatment options are not efficient or present too many adverse effects. It is known that metabolic regulation is crucial for the maintenance of normal cell function and homeostasis, but differ in the disease state. A promising approach might therefore be to interfere with metabolic cascades that are implicated in immune cell functionality during disease. The group will conduct metabolic profiling of immune cells with the aim to identify cell- or disease-specific metabolic signatures or pathway specificities. A better understanding of the immunometabolism will be an important step for the further development of targeted therapeutic strategies. The project will be conducted in collaboration with German partners at the Technische Universität Braunschweig, the Helmholtz Centre for Infection Research and the Medical Faculty of the University of Mannheim together with the University of Heidelberg.

Prof Mahesh Desai, Principal Investigator of the “Eco-Immunology and Microbiome” research group at LIH’s Department of Infection and Immunity will initiate a project on inflammatory bowel disease (IBD), a group of disorders of the gastrointestinal tract for which the pathogenesis mechanisms are poorly understood. He and his team will investigate the role of mucobiomes in the pathogenesis of IBD. Mucobiomes are communities of colonic mucus-degrading bacteria whose activities are regulated by dietary fibres. For this project, culture collections of mucobiomes from patients will be established, which will be followed by mechanistic studies in gnotobiotic mice. The research team aims to identify the underlying immune pathways related to mucus deterioration and to understand mucobiome alterations that occur during the commonly employed anti-TNF therapies to treat IBD. The ultimate goal of this research would be to identify the disease-causing immune pathways and to enhance the anti-TNF therapies in IBD by employing next-generation prebiotic fibres that would modulate the activities of mucobiomes. The project involves multiple collaborations with Centre Hospitalier de Luxembourg, the University of Michigan Medical School, US, the Johns Hopkins University, US, and the Gothenburg University, Sweden.

Dr Bassam Janji, Deputy Head of the Laboratory of Experimental Cancer Research at LIH's Department of Oncology, will explore a key and timely issue related to designing innovative approaches for the improvement of immune checkpoint blockade therapies in cancers. Indeed, the encouraging and ground-breaking success of immune checkpoint blockade-based cancer immunotherapy has been seriously challenged by clinical observations showing that only a small fraction of patients gain durable and sustained clinical benefit from this therapy. Therefore, the next challenge in the field of cancer immunotherapy is the clinical development of combinatorial approaches to extend the use and benefit of immune checkpoint inhibitors to a large number of cancer patients, in particular non-responder patients. Through its clinically oriented and basic research aspects, the project will allow the development of innovative strategies aiming to use autophagy inhibitors to switch cold immune desert tumours to hot immune inflamed tumours able to drive anti-tumour effector immune cells to the tumour bed, along with a combination of T-cells and macrophages immune checkpoint blockades. Dr Janji hopes that the translational aspect of the project will lead to the establishment of valuable and relevant preclinical models and provide the proof of concept to set up clinical trials using pioneering combination therapies.

*decision from Deutsche Forschungsgemeinschaft (DFG) pending for bilateral project proposal