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Glioblastoma (GBM) remains the most aggressive of all primary brain tumors and no effective treatment is available so far. The recent success of immune checkpoint inhibitors in several cancers paved the way for the rehabilitation of anticancer vaccines. However, critical factors challenge the effica

Fibrotic diseases, notably liver diseases, are a major burden worldwide. Ablating myofibroblasts (MFs), the key effectors of fibrosis, has recently emerged as an innovative anti-fibrotic strategy. In liver fibrosis, MFs largely derive from hepatic stellate cells (HSCs) but also from portal fibroblas

Currently, standard cancer treatment includes surgery, external radiotherapy, and chemotherapy and / or immunotherapy. However, despite all the progress made in recent decades, there are still serious clinical situations offering very few or no therapeutic options to patients, leaving them with a su

Extracellular Vesicles (EVs) denote a variety of nanoparticles released by cells into surrounding milieu and circulating in biofluids such as blood. These lipid bilayer vesicles transport protected bioactive materials and may thus represent a valuable informative resource on health status and diseas

The primary objective of the PREDIGANG project is to develop a reliable predictive biomarker for the tumor response to anticancer immunotherapies targeting the O-acetylated form of the GD2 ganglioside (OAcGD2 ) using Patient Derived tumors Xenografted in mice. The secondary objective is to better un

The LPCBioMab project wants to develop a targeted therapy of atherosclerosis associated with a companion diagnostic tool. We aim to engineer biomimetic, biocompatible ApoA1-based lipoprotein complexes (LPC) inspired by nature, containing a natural compound for metabolic regulation of intimal macroph

In vivo gene therapy using recombinant adeno-associated viral vectors (rAAV) showed promising benefits for the treatment of genetic disorders as illustrated by Luxturna®, Glybera® and Zolgensma® FDA and EMA approvals. However, there are still scientific locks to overcome for a successful clinical tr

BACKGROUND: Foxp3+ regulatory T cells (Tregs) are crucial actors in the control of autoimmune and chronic inflammatory diseases. Indeed, functional or quantitative defects of Tregs have been associated with many autoimmune diseases in humans. Their stimulation represents a promising therapeutic stra

Drug efficacy/toxicity prediction is a major concern in modern research and development. To prevent adverse drug reactions, in silico approaches assessing ADMET (absorption, distribution, metabolism, excretion, toxicity) have become an integral part of early drug discovery. We will develop an origin

The SerozeroSEP project aims to study the serotonin 5-HT7 receptor as a new therapeutic target for the treatment of multiple sclerosis (MS), a disease caused by dysfunction of the immune system, leading to brain damage (demyelination, axonal injury and neuroinflammation). While treatments exist to s

The ULTIMO project aims at developing the quantitative imaging of myelin lipid membranes with inhomogeneous Magnetization Transfer (qihMT) and at validating this new MRI technique as a biomarker of myelin, sensitive to its pathological conditions. By allowing quantitative and non-invasive mapping of

We have recently discovered a new technology that uses microtubules as nanoplatforms to detect biomolecular interactions in cells. This technology is particularly effective in quantifying RNA:protein interactions for which other existing methods offer few alternatives. Here, we propose to develop th

We have identified a novel protein-protein interaction of the ERK MAP kinase with MyD88, an adaptor of inflammatory signaling, and showed that this interaction is required for Ras-dependent cancers. We developed a small molecule, EI-52, which induces apoptosis of cancer cells and inhibits tumor grow

Despite the many therapies being studied for Alzheimer's disease (AD), a cure does not yet seem to be within reach. A more holistic approach of the disease and its treatment that takes into account its multifactorial etiology, should help us to establish new conceptual paradigms and more efficient t

Thrombospondin 1 (TSP1), a major protein from platelet alpha granules being overexpressed in cardiovascular diseases, plays a key role in haemostasis and thrombosis. TSP1 interaction with CD47 enhances platelet adhesion as well as aggregation while stabilizing platelet aggregates. Thus, targeting th

Down syndrome (DS) is the most common form of intellectual disabilities in the world, caused by trisomy of human chromosome 21. DS still shows a high prevalence with a strong socio-economic impact on both families and society and constitute a major unsatisfied medical need. Among the few key driver

Adiponectin (Adpn), an adipokine which displays insulin-sensitive properties, is a very promising target to tackle the cardiometabolic complications associated with Type 2 Diabetes (T2D). Design of Adpn-mimicking drugs has been so far hampered by the difficulties encountered to produce this therapeu

The induction of protective immune responses in the respiratory tract remains one of the main challenges in the vaccine field. The emergence and success of messenger RNA (mRNA) vaccines, as seen by the control of Covid-19 pandemic, allowed to envision the induction of specific mucosal immune respons

FIIBRE is a multidisciplinary project that will develop and validate a new class of antibiotics, targeting in priority ESKAPE and multi-resistant bacterial strains in order to limit the emergence and spreading of new resistances. This original therapeutic exploits a new molecular target, never explo

Alzheimer’s disease (AD) is a slowly progressing dementia made of two pathophysiological mechanisms - the amyloid and the Tau pathologies – associated with neuroinflammation. Yet, targeting only one mechanism remained elusive to be efficient against AD. Considering the entire pathophysiology of AD a

Atherothrombosis, a major cause of cardiovascular diseases including myocardial infarction, is a process that starts early in childhood and is accelerated by cardiovascular risk factors. The atherogenesis process is targeting initially well-defined arterial sites at risk such as bifurcations, charac

Lung emphysema is a major pathologic component of chronic obstructive pulmonary disease (COPD) characterized by damage to the air sacs in the lungs. The symptoms are indeed caused by the physical destruction of the elastic fibers in the lung parenchyma, together with a sharp increase in cell senesce

The ANTARBioTic project is fitting with the objectives of Biomedical Innovation, in line with the “Antibiotic Resistance” program. Two sentences caught our attention in a recent report of the WHO on antimicrobial resistance, which are pushing ANTARBioTic ahead. The first one states: “overall, the cl

Brain stimulation or neuromodulation is a promising therapeutic tool for the treatment of many neuro-psychiatric conditions (epilepsy, chronic pain, stroke, depression, etc.). Its success is currently limited by its invasiveness and its lack of precision. Indeed, current stimulation approaches reach

Cancer immunotherapies are here to stay. However, only a minority of patients experience durable survival from these therapies, highlighting the urgent need to develop immunotherapies with improved effectiveness and patient response rates. One mechanism used by tumors to evade the immune response is

Venous Thromboembolic Events are serious, life-threatening conditions, with an annual incidence of 120 over 100 000 people in France. Clinical and biological risk factors for thrombosis cannot be determined for about 50% of patients, making it difficult to assess the risk of recurrence and to adapt

The depolymerized derivatives of polysaccharides (PS) called oligosaccharides (OS) emerge as very promising bioactive coatings for multifunctional nanoparticles (NP), intended for targeted therapy in oncology. Contrary to their PS of origin, the OS have more defined structures and bioactivities, whi

Enhancement of lung tissue regeneration and functional recovery following an acute pulmonary insult by regenerative therapy based on the use of heparan sulfate mimetics (HSM) is a promising approach for the treatment of diffuse alveolar damage (DAD), observed in acute respiratory distress syndrome (

Human Endogenous Retroviruses (HERVs) represent 8% of our genome and result from ancient infections by retroviruses. Since HERVs are silenced in normal cells while aberrantly expressed in some tumors, they may represent a source of tumor antigens able to induce strong immune responses. However, expl

Asthma is one of the most common chronic diseases with an increased prevalence in developed countries. Severe asthmatic patients are resistant to the current therapeutic management, leading to dramatically increased mortality risk. Those patients definitely need new treatments. We recently unveiled

The goal of this project is to develop and characterize an innovative combined thrombolytic and anticoagulant approach for ischemic stroke. Ischemic stroke is a neurological deficit resulting from an insufficient blood supply to the brain due to the presence of a clot in a cerebral artery. In France

Though mainly discussed in the context of tumor control, immunotherapy has emerged as an effective strategy to combat pathogen infection by blocking immune checkpoint signaling. Likewise, the continued success of immunotherapies relies on the identification of novel targets, more effective treatment

Tuberculosis (TB), caused by the Koch bacillus Mycobacterium tuberculosis (Mtb), is a millennial global health problem, still responsible today for 1.4 million deaths and approximately 10 million new cases each year. Facing the lack of efficacy of vaccination, the emergence of antibiotic-resistant s

Mycobacterium tuberculosis, the causative agent of tuberculosis, kills 1.6 million people each year. Current oral antibiotic therapy is restrictive, time-consuming and has many side effects. With the emergence of antibiotic-resistant strains and the weaknesses of oral therapy, there is an urgent nee

Multi drug resistant (MDR) bacteria, notably Klebsiella pneumoniae (Kp) and Pseudomonas aeruginosa (Pa), are a major global threat. The development of alternative anti-infectious therapies is thus crucial. In this respect, monoclonal antibodies (mAbs) targeting bacterial virulence factors offer high

Prolongation of life expectancy is associated with an increase of age-related diseases (ARD). Most ARD exhibit multi-tissue disruptions leading to functional loss and patients’ quality of life impairment. Slow and subtle development of age-related tissue alterations delay diagnosis, resulting in poo

Our project aims at an original strategy to propose novel and innovative antimalarial drugs based on the design of small molecules that specifically target the G-quadruplexes structures present in the mitochondrial genome of Plasmodium falciparum. Guanine-rich DNA and RNA sequences can fold into fo

Incidence of chronic neurodegenerative disorders like Alzheimer's disease is estimated to double by 2030 and triple by 2050 with the global ageing of population while there is still no curative treatment yet. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) overexpression is co

We have shown that the TREK1 potassium channel is involved in the analgesic effect of morphine but not in its adverse effects, and that direct activation of this channel is analgesic and well tolerated. Based on the recent development of new TREK1 activators, this project aims to (1) determine in wh

The recent SARS-CoV-2 pandemic has highlighted the need to develop new antivirals against RNA viruses that are responsible for more than a third of new emerging or re-emerging infections. As many RNA viruses use cellular helicases during their infectious cycle, these proteins have become promising t

Mucins are infections protective glycoproteins of the intestinal wall displaying on their surface sialic acids in important quantities such as N-acetylneuraminic acid (Neu5Ac) and its C-9 acetylated analogue (Neu5,9Ac2). Neu5Ac serves as a metabolic substrate for the development of specific bacteria

The current pandemic made it clear how important antiviral drugs are; not only against coronaviruses, but against many other families of viruses as well, which can lead to life-threatening conditions, especially in children. As French experts in antiviral drug research and development, the fight aga

Ischemic stroke in sepsis shock is associated with increased mortality and long-term cognitive impairment. Due to its critical position, the brain vessel recanalization is an emergency. However, in sepsis context, the therapeutic strategies available are limited. Thus, innovative approaches targetin

SARS-CoV-2 entry into host cells depends on binding of the viral spike (S) protein with the surface receptor ACE2 and subsequent priming by TMPRRS2 allowing membrane fusion. Soluble recombinant ACE2 was proven to bind to the S protein, and reduce SARS-CoV-2 entry in Vero-E6 cells and engineered huma

Donor-specific tolerance has long been the crowning achievement in transplantation, with the ultimate goal to avoid the complications of long-term immunosuppression such as cancer. In patients, immune tolerance, defined as a state wherein donor and recipient immune cells coexist, has been successful

Insulin degrading enzyme (IDE) is a zinc metalloprotease that hydrolyses insulin and other amyloidogenic peptides. Besides, IDE is not limited to its proteolytic activity and acts also as a partner in protein quality control mechanisms. With all of these proteolytic and non-catalytic roles, IDE is l

Despite a significant decrease in number of Plasmodium falciparum-related deaths in recent years, malaria remains a major public health problem. Resistance of parasites to anti-malarial drugs could soon lead to a resurgence of the disease and calls for the need of developing new interventional strat

Gold Quantum Clusters (GQCs) are a class of ultra-small particles presenting tunable photoluminescence (PL) in the first (NIR-I) and second (NIR-II/SWIR) near-infrared windows, making them appealing tracers for high resolution imaging of blood vasculature in mice, as demonstrated by Team 1. Interest

Metabotropic glutamate receptor 5 (mGluR5) is highly expressed in brain regions responsible for memory and learning. Aberrant mGluR5 signaling and associated synaptic failure are now considered as an emerging pathophysiological mechanism of Alzheimer’s disease (AD). Therefore, mGluR5 represents an a

The peptidoglycan, a heteropolymer and major component of the bacterial cell wall, is essential for cell integrity. It surrounds completely the cell and its synthesis is coordinated with cell growth and division. Its assembly is accomplished by periplasmic protein complexes involving synthetases, sc