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The goal of this project is to develop an innovative strategy to target the xenoreceptor PXR to degradation for multiple medical benefits. The nuclear receptor PXR plays a central role in the metabolism of endo- and xenobiotics, i.e. toxins and drugs. When activated, PXR coordinates expression of dr

Gene transfer is a new therapeutic opportunity to cure disease without efficient treatment. Most of the tries today rely on viral carrier, with limitations that needs to be circumvented. An alternative to the use of viruses is the synthetic carriers. However, the gene transfer efficiency of syntheti

Glycogen storage disease type III (GSDIII) is a rare (incidence: 1:100000) autosomal recessive disorder resulting from the lack of glycogen debranching enzyme (GDE) deputed to glycogen linearization in different tissues. Although GDE is expressed in all the tissues, the disease manifestation is prim

In the past 5 years, a protein from prokaryotes has revolutionized biology in ways not seen since PCR in the 80s. CRISPR (Clustered regularly interspaced short palindromic repeats) is an adaptive immunity system for bacteria and archaea that fights off viruses by keeping a DNA record of past infecti

Understanding pain, and relieving its symptoms, represent crucial challenges on scientific and medical grounds, with the available panoply of analgesics largely insufficient. Notably to remedy this situation, we have witnessed recently a marked interest in the analgesic solutions elaborated by mothe

Histidine-rich peptides that were designed and investigated in our laboratories exhibit a large variety of biological functions that can be tuned by subtle sequence variations, pH, salt and other environmental conditions. These LAH4 peptides exhibit potent antimicrobial and pore forming activities,

With increasing life expectancy, neurodegenerative diseases such as Parkinson’s or Alzheimer’s disease are expected to affect an ever increasing number of people, potentially putting severe strain on healthcare systems around the world. These diseases are challenging in term of diagnostic because of

Myelin is an essential component of the central nervous system (CNS) allowing fast electric propagation through the neuronal networks and supporting neuron integrity via trophic support. In the healthy CNS, myelin turnover in response to neuronal activity has been demonstrated to contribute to memor

Immune tolerance remains the « Holy Grail » in transplantation because no more progress has been seen in long-term outcomes. Dendritic cells (DCs) are specialized cells in the pro and anti-inflammatory balance of the immune response. Moreover, subsets of DCs, identified in humans, appear to have the

There is a major health problem due to the environmental and occupational related exposures to mineral particles, metals, and dust. The impact on health is considerable in terms of prevalence, morbidity and healthcare costs. Pathologists never report the presence of a possible metal-related etiology

Deafness and balance defects are the most prevalent inherited sensory disorder in humans and is a major concern and a serious burden for Public Health. Today, clinical prevalence of deafness is approximately 1 in 700 newborn. About 80% of deafness cases, associated or note with balance defect, are a

Platelets are blood cells allowing to prevent or stop hemorrhage. Transfusion of platelets from blood donors is a life-saving treatment for patients with very severe bleeding or patients with low platelet counts due to defect of platelet production from the bone marrow failure upon solid cancers or

Tumor Necrosis Factor alpha (TNFa) is a homotrimeric cytokine of the immune system whose overproduction has been associated with several chronic inflammatory diseases and especially rheumatoid arthritis (RA). Clinically approved inhibitors of TNFa include monoclonal antibodies (infliximab, adalimuma

The early detection and diagnosis of infection by microbial pathogens is essential to establish an adapted therapy by identifying and characterizing the pathogens, ideally in the context of personalized medicine. A quicker detection without fastidious culturing steps of any virulent or opportunistic

The objective of the present proposal is to determine how the transcriptase machinery of Influenza A virus (IAV) is targeted to chromatin, to explore the global impact of the virus on host chromatin structure, and to gain preliminary insight on the effect of a selection of epi-drugs on the viral cyc

Women's fertility is linked to their oocytes quality. Indeed, before ovulation, oocytes have to resume their meiosis, then to activate the zygote upon fertilization and finally to support the embryonic development for the 5 days of tubal transit before implantation in the uterus. This represents a b

Current neurodegenerative models derived from human induced pluripotent stem (iPS) cells have the capacity to recapitulate cellular and molecular processes leading to the disease, creating novel avenues to model and understand the pathological development / pathobiology. Regarding retinal disorders,

The objective of this project is to develop a new biological treatment for severe heart failure, based on the controlled biomaterial-mediated administration of extracellular vesicles (EV) secreted by cardiovascular progenitor cells. The underlying rationale is that the benefits of stem cells transpl

Most current approaches for identifying small molecules biological targets generate lists of potential biological targets. From these lists it is then highly challenging and time consuming to identify the functional biological target(s). The goal of the project is to validate a new framework that fa

There is crucial and unmet need for efficient therapies against chronic pain. Mambalgins represent a real opportunity to develop novel analgesics. These natural peptides specifically block Acid-Sensing Ion Channels, a set of ion channels emerging as important targets in pain. The three isopeptides p

Bioconjugates have become essential tools for biomedical research, diagnosis and therapy. A second generation of bioconjugates begins to emerge. It consists in doubly-modified proteins, which have optimized properties and / or open new fields of application such as bimodal medical imaging or therano

Multidrug resistance is a major public health problem requiring urgent development of new antibiotics and thus identification of new bacterial targets, as pointed out by the World Health Organization again this year. The core of the consortium involved in this project has initiated a decade ago the

There is currently an urgent need for new antibiotics in order to overcome the steady emergence of multidrug-resistant bacteria and the associated human and economic cost. For the development of new antimicrobial agents, two major issues must be overcome: the difficulty to permeate bacterial membran

The first aim is to define the expression of IL-34 and its receptors (CSF1R, CD138 and PTPz) in normal fluids, cells and tissues and investigate the molecular role of IL-34 on human cells. We demonstrated that in rat, IL-34 can be an immunoregulatory molecule on the effector immune response through

Heart Failure (HF) is an epidemic of the 21st century. This chronic disease is a major public health problem due to its high prevalence (26 million patients worldwide), frequent hospitalizations and economic impact of associated direct and indirect costs. With the aging and industrialization of the

The peroxisome proliferator-activated receptor-gamma (PPARy) is a protein of the nuclear receptor superfamily which naturally binds lipids and acts as a transcription factor. Initially described as the "master" gene of adipogenesis, PPARy activation also potentiates the action of insulin, justifying

Lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) are major causes of morbidity and death worldwide for which therapies with efficient and prolonged local activity are much needed. Though it is considered as a promising approach to treat lung diseases, gene therapy still

The Parkington project aims at proposing a novel cell therapy approach for the treatment of neurodegenerative diseases, in particular for Parkinson’s and Huntington’s disease (PD and HD). In the past decade, pluripotent stem cells have provided unprecedented access to human cell types, with a specia

Almost every physiological system is controlled by G protein-coupled receptors (GPCRs). As such, these receptors are considered as a most popular class of drug targets with potential applications in many different pathological processes such as neurological and metabolic disorders, inflammation, can

The pharmacokinetics of many drugs, namely their resorption, distribution, metabolism and elimination depend on the hour of administration. As the consequence, these drugs are more effective and/or better tolerated if taken at appropriate time. Synchronization of drugs administration with the circad

Combined [18F]PET/NIRF imaging (Positron Emission Tomography/Near Infra Red Fluorescence) hold a huge potential to transform patient diagnosis and care. Such a combination conjugates the non-invasive whole-body diagnosis of PET with the intraoperative imaging-guided surgery or ex vivo histopathology

Tuberculosis is the second infectious disease leading to mortality after AIDS and one of the top ten causes of death worldwide. The emergence of multidrug-resistant strains had complicated the management of tuberculosis and constitutes a serious threat for the control of the pandemic. Drugs of the ß

Processes of mammalian cell culture have become essential for the production of recombinant therapeutic proteins since more than 70% of the monoclonal antibodies for therapeutic use are produced by CHO cells (Chinese Hamster Ovary). As a result, the PAT (Process Analytical Technology) approach devel

Our most cherished sense, vision, begins with the process of phototransduction, a process performed by the highly specialized photoreceptor cells of the retina. Seven transmembrane proteins are responsible for light capture and they have evolved into many different forms through evolution. In majori

The present project is based on a new concept using the chemical properties of radical species to fight both malaria and schistosomiasis diseases. Our project is focused on the preparation of a stable prodrug (alkoxyamine as dormant radical, R1R2NOR3), which will be selectively coordinated by the fr