Research groups & topics

picto IMS cancer

Nano-translational laboratory – Alexandre Detappe

Molecular Mechanisms and Targeted Therapeutic Intervention for Neuroprotection​ – Dominique Bagnard

Chemogenomic and Medicinal Chemistry​ – Frédéric Bihel

Immune-microenvironment interaction in health and disease​ – Christopher Mueller

Integrative Chemical Biology – Dominique Bonnet

BioFunctional Chemistry​ – Alain Wagner

Poly (ADP-ribosyl)ation and genome integrity​ – Françoise Dantzer

Platform of chemical biology​ – Pascal Villa

picto IMS maladies intestinales
Neuroimunology and peptide therapeutics – Sylviane Muller
picto IMS maladies inflammatoires-04

Neuroimunology and peptide therapeutics – Sylviane Muller

Immune-microenvironment interaction in health and disease – Christopher Mueller

Integrative Chemical Biology – Dominique Bonnet

Chemogenomic and Medicinal Chemistry – Frédéric Bihel

Platform of chemical biology – Pascal Villa

picto IMS douleur

RCPGs, Pain and inflammation – Frédéric Simonin

Integrative Chemical Biology – Dominique Bonnet

Chemogenomic and Medicinal Chemistry – Frédéric Bihel

Platform of chemical biology – Pascal Villa

picto IMS maladies neurologiques

Neuroimunology and peptide therapeutics – Sylviane Muller

Molecular Mechanisms and Targeted Therapeutic Intervention for Neuroprotection​ – Dominique Bagnard

Chemogenomic and Medicinal Chemistry​ – Frédéric Bihel

Platform of chemical biology​ – Pascal Villa

picto IMS maladies rares

Neuroimunology and peptide therapeutics – Sylviane Muller

Chemogenomic and Medicinal Chemistry​ – Frédéric Bihel

Platform of chemical biology​ – Pascal Villa

picto IMS maladies infectieuses

Chemogenomic and Medicinal Chemistry​ – Frédéric Bihel

Platform of chemical biology​ – Pascal Villa

picto IMS diagnostic
Molecular Mechanisms and Targeted Therapeutic Intervention for Neuroprotection​- Dominique Bagnard
picto IMS techno

Molecular Imaging​ – Frédéric Boisson

Platform of chemical biology​ – Pascal Villa

BioOrganic Mass Spectrometry​- Sarah Cianférani

Research groups

Nano-translational laboratory

The research laboratory of Prof. Alexandre DETAPPE is located at the Institut de Cancérologie Strasbourg Europe (ICANS) and is affiliated to CNRS UMR7178 and to the ITI Drug Discovery and Development Institute. Its overarching goal is to improve cancer treatment with biotechnology and materials chemistry, employing a materials science-centric approach to develop new therapies to :

  • reduce the side effects induced by current chemotherapies
  • control the modulation of the immune system,
  • assess in vivo the tumor response and the immune system response to novel cancer therapies.

More specifically, we develop novel smart drug delivery systems, immunonanotherapies, supercharged antibody drug conjugates, and novel small molecules. Our expertise focuses on multiple myeloma and breast cancer models, however, we explore novel research opportunies as well as they arise. Our first focus is to translate all of our preclinical work into clinical trials, with the ultimate aim of improving cancer patients treatments. With the expertise of our clinicists, we are currently validating novel nano-based therapeutics for tumor sensitization, novel biosimilars for breast cancer treatments, and novel monoclonal antibodies in various ongoing Phase I/II clinical trials.

 

UMR 7178 CNRS-Unistra,  Institut de Cancérologie Strasbourg Europe (ICANS),

17 Rue Albert Calmette, 67200 Strasbourg

a.detappe (at) icans.eu

Neuroimunology and peptide therapeutics

The research laboratory of Prof. Sylviane Muller is located at the Institut de science et d’ingénierie supramoléculaire (ISIS) in Strasbourg. It depends on the CNRS-Unistra Unit Biotechnology and cell signalling (Ecole supérieure de biotechnologie de Strasbourg). Sylviane Muller co-leads the research team Neuroimunology & peptide therapy, which is focused on the understanding of misdirected immune responses occurring in autoimmune and inflammatory diseases, and on the discovery of new druggable molecules designed to specifically control these disorders. More precisely, the team members :

  • decipher the cellular and molecular immune circuits that are altered in patients and murine models with a special focus laid on the lysosomal autophagy processes that are dysregulated in these settings
  • study the behavioural disturbances that progressively occur in model mice with neurological autoimmune diseases
  • develop strategies that specifically target the identified defective immune processes. The peptide P140 discovered in the team is currently evaluated in phase III clinical trials for Lupus. All these questions are investigated using approaches of molecular and cellular biology, imaging, immunochemistry, peptide chemistry, material chemistry for molecule targeting/vectorization and behavioural approaches in animal.

Biotechnologie et signalisation cellulaire (UMR7242 CNRS-Unistra)

300 boulevard Sébastien Brant, CS 10413, 67412  ILLKIRCH CEDEX

sylviane.muller (at) unistra.fr

Group leader :
Dominique Bagnard

Molecular Mechanisms and Targeted Therapeutic Intervention for Neuroprotection

Therapeutic innovation involves deciphering the molecular interactions that regulate cellular functioning in order to develop drugs capable of modulating these interactions and correcting their dysfunctions. This concept of molecular interactions takes on a particular dimension with the membrane proteins that provide the interface between the extracellular and intracellular environment, which is an essential site for the transmission of signals controlling the cell. Dr. Bagnard’s research laboratory is working on the development of peptide compounds that act as interfering agents modulating the interactions between membrane proteins. These peptides target the transmembrane domains of membrane receptors and have already demonstrated their therapeutic potential for the treatment of cancers such as glioblastoma or metastatic breast cancer but also in the case of demyelinating diseases such as multiple sclerosis. With more than fifteen years of experience in this unique strategy, the laboratory has developed a know-how materialized by a platform for the design and preclinical evaluation of these therapeutic transmembrane peptides applicable to all forms of therapeutic compounds. From the use of in silico modeling to in vivo animal models of pathologies, the laboratory has the expertise and comprehensive technical means to obtain patentable compounds with a high transfer potential. The work carried out also takes into account the need for molecular tools for predicting the evolution of a disease or the response to a treatment. The molecular tools developed in the laboratory aim to validate experimental treatments while contributing to the monitoring of the therapeutic response.

 

INSERM ERL 1321 – Biopathologie de la Myéline, Neuroprotection et stratégies thérapeutiques (Dir : Pr G. Mensah-Nyagan),

Site d’Illkirch Pôle API Bâtiment E – 300 Boulevard S. Brant

bagnard (at) unistra.fr

Group leader :
Sarah Cianférani

BioOrganic Mass Spectrometry

The BioOrganic Mass Spectrometry laboratory (LSMBO) belongs Analytical Sciences Department of the Institut Pluridisciplinaire Hubert Curien (IPHC, www.iphc.cnrs.fr, CNRS Université de Strasbourg UMR7178). The LSMBO is hosting an IBiSA-certified proteomic platform (Strasbourg Grand Est Proteomic Platform) and is the Strasbourg node of the French Proteomic Infrastructure (ProFI, www.profiproteomics.fr). The LSMBO is a 35 scientists team that has a 30 year-experience in the structural study of peptides and proteins by mass spectrometry. The laboratory is renowned for developing new methods in quantitative proteomics, bioinformatics for proteomics and structural mass spectrometry for the analysis of protein/protein interactions in large complexes. Besides that, long term collaborations with several pharmaceutical companies cover topics such as full characterization of natural and/or recombinant proteins used in human therapy, toxicoproteomics, protein/drug interaction.

 

Field of expertise:

  • Sample preparation for proteomic analysis (1D or 2D gels, liquid digestion, PTMs enrichment…)
  • Quantitative label-free proteomics
  • Targeted quantitative proteomics (LC-SRM/PRM)
  • PTM identification and quantification (phosphorylation, etc.)
  • Bioinformatics for proteomics (de novo sequencing),
  • Interactomics
  • Recombinant protein analysis (eg monoclonal antibodies)
  • Native MS and Ion Mobility of noncovalent complexes
  • HDX-MS
  • cross-linking MS

UMR 7178 CNRS-Unistra, Institut Pluridisciplinaire Hubert Curien (IPHC), 

23 rue du Loess, BP 28, 67037 Strasbourg Cedex

sarah.cianferani (at) unistra.fr

Group leader :
Frédéric Simonin

RCPGs, Pain and inflammation

G protein coupled receptors (GPCRs) represent the largest family of membrane receptors in eukaryotes with more than 800 members in humans. They are stimulated by a wide variety of extracellular signals and are involved in many physiological and pathophysiological processes including neurotransmission, cell division and differentiation, chemotaxis, inflammation and pain. As such, they represent preferred targets for the development of new drugs. Our team is particularly interested in the role of different GPCRs in the development of pain and associated inflammatory processes as well as the mechanisms that regulate GPCR signaling. Our approaches include the development of pharmacological (antagonists) and genetic (KO mouse) tools for these different targets as well as new therapeutic strategies for the treatment of pain.

UMR 7242 CNRS-Unistra, Ecole Supérieure de Biotechnologie de Strasbourg (ESBS),

300 Boulevard Sébastien Brant, 67412 Illkirch

 

frederic.simonin (at) unistra.fr

Group leader :
Frédéric Bihel & Esther KELLENBERGER

Chemogenomic and Medicinal Chemistry

The Chemogenomics and Medicinal Chemistry (CCM) team belongs to the Laboratory of Therapeutic Innovation (UMR7200) of the Faculty of Pharmacy in Strasbourg. At the interface of several disciplines such as chemoinformatics, organic and medicinal chemistry or structural biology, the CCM team aims to rationalize and accelerate the discovery of bioactive molecules and optimize them to make them drug candidates. The chemoinformatics group led by Prof. E. Kellenberger and Dr. D. Rognan, is developing bio- and chem-informatic methods to predict the binding of “small” molecules to their target proteins, for applications in virtual chemical library screening and in profiling the biological activity of a molecule. Our models integrate traditional approaches to drug design (docking, pharmacophore) and learning on a statistical basis (artificial intelligence). The Medicinal Chemistry Group, led by Dr. F. Bihel and Dr. M. Schmitt, develops innovative and functionalized molecular scaffold with a goal of molecular diversity for therapeutic purposes, and has a recognized expertise in the structural optimization of bioactive molecules for the development of drug candidates. With its complementary expertise, the CCM team is involved in many therapeutic projects, targeting the fields of cancer, pain, neurodegenerative diseases and infectious diseases, among others. The valuation of research projects (patents, licenses, creation of start-ups) is an important objective of the team, which can claim the creation of a start-up (Biodol), and several patents under license (molecules or software).

Using artificial intelligence as well as cutting-edge concepts in organic and medicinal chemistry, the CCM team designs, synthesizes and functionalizes innovative molecular scaffold applied to drug discovery.

UMR 7200 CNRS-Unistra, Faculté de Pharmacie,

74 route du Rhin, 67401 Illkirch, cedex, FRANCE

frederic.bihel (at) unistra.fr

Group leader :
Frédéric Boisson

Molecular Imaging and Radiobiology

The team’s activities are concentrated around two main research areas. The first one is the development of imaging devices for in-vivo visualization of mechanisms at the molecular level in preclinical imaging. Our philosophy is to go beyond limits of commercial solutions to make previously unobserved biological processes accessible. The second main research focus is the labeling of molecules (anti-bodies, peptides, macro- and small molecules) with various PET and SPECT isotopes.

The team offers all the expertise needed for instrumental development, quantification and signal processing in the field of imaging, and more specifically the “nuclear” imaging modalities such as PET and SPECT. This expertise is also strengthened by other internal skills in radiochemistry through the labeling of molecules (antibodies, peptides, macro- and small molecules) with various isotopes dedicated to PET and SPECT imaging produced thanks to the Cyrcé cyclotron.

UMR 7178 CNRS-Unistra ,Institut Pluridisciplinaire Hubert Curien (IPHC),

23 rue du Loess, BP 28, 67037 Strasbourg Cedex

frederic.boisson (at) iphc.cnrs.fr

Group leader :
Christopher Mueller

Immune-microenvironment interaction in health and disease

For example, we have recently shown that lymphatic endothelial cells create a niche for a subtype of lymph node macrophages involved in the anti-infectious and anti-cancer immunity.

In order to model diseases in humans and towards personalized medicine, the laboratory is reconstructing organoids in vitro, such as immuno-competent and innervated human skin. In addition, we have exploited the natural affinity of arboviruses for human skin immune cells to generate vectors targeting macrophages and dendritic cells.

  • Isolation et cultures en 2D et 3D de cellules murines et humaines primaires
    et de cellules humaines neuronales dérivées des iPSCs. / Isolation and 2D +
  • Transparisation et microscopie à fluorescence d’organe entier

 

 

UPR3572 CNR – Institut de Biologie Moléculaire et Cellulaire, 
15 Rue René Descartes, 67000 Strasbourg

c.mueller (at) ibmc-cnrs.unistra.fr

Group leader :
Pascal Villa

Platform of chemical biology

PCBIS offers its services to public and private laboratories

 

  • Assay development : The services “High Throughput Screening” and “Target Libraries” set up miniaturized and automated assays , produce and validate biological models (target based or cell based). This can be done from cloning to protein expression (soluble proteins and stable or transient cell lines)
  • High Throughput Screening (HTS) : The service “HTS” validates and runs automated screening of chemical libraries in order to identify active compounds.
  • Microfluidics : The service “Microfluidics” develops new models and tools in order to perform innovative lab on a chip experiments.
  • Chemical libraries : The service “Chemical librairies” manages compound collections, performs structure activity relationship (SAR) analysis and contributes to hit optimization.
  • ADME-Tox : The service “TechmedILL” establishes the physicochemical and pharmacokinetics of compounds (solubility, log D, pKa, chemical and plasmatic stability, membrane permeability, metabolism, pK in vivo…) and cellular toxicity.
  • Training : our engineers train and supervise students and researchers who want to use our technologies and facilities..

 

 

 

  • Identification de candidats médicaments par des techniques innovantes de fluorescence en tests cellulaires et moléculaires miniaturisés
  • Analyse des propriétés pharmacologiques et précliniques des composés
  • Modèles animaux (asthme, inflammation…)
UAR 3286 CNRS-Unistra, PCBIS ESBS and Faculty of Pharmacy
300 Boulevard Sébastien Brant 67412 Illkirch

pvilla (at) unistra.fr

Group leader : Françoise Dantzer

Poly (ADP-ribosyl)ation and genome integrity

The research of our team aims to clarify the complex role of poly(ADP-ribosyl)ation in the cellular processes controlling genome integrity and tumorigenesis. Previous work of the team has focused on dissecting the properties of the enzymes catalyzing the synthesis of poly(ADP-ribose) (PAR) in response to DNA damage, the poly(ADP-ribose) polymerases PARP1 and PARP2, and the enzyme degrading PAR, known as poly(ADP-ribose) glycohydrolase (PARG).

We defined PARP1 as a sensor of DNA strand breaks, playing essential functions in the spatial and temporal organization of their repair through the local synthesis of PAR and recruitment of DNA repair enzymes at the site of the lesion. Its inhibition is currently used in clinical trials to potentialize the cytotoxic action of antitumoral drugs and radiation therapy or to target repair deficient cancers (BRCAmut). PARP2 has also been shown to contribute to genome integrity. By combining biochemical studies and characterization of PARP1 and PARP2-deficient cellular and animal models, we uncovered redundant functions of both proteins in DNA repair and more specific activities in the regulation of transcription, chromatin organization and cell differentiation. Finally, we identified prime functions of PARG to prevent detrimental accumulation of PAR upon irradiation and prolonged replication stress.

These last years, we undertook the biochemical and functional characterization of novel PARP members, PARP3 and PARP9. While PARP9 is described as a novel actor in stress-induced double-strand break repair, our PARP9 knockout mouse model does not show obvious defects in the repair of programmed double-strand breaks. We found that PARP3 plays important functions in cell response to double-strand breaks, mitotic progression, epithelial-mesenchymal transition and stemness in breast cancer.

Our challenge today is to further dissect the biochemical and biological properties of PARP3 in double-strand break repair and tumorigenesis in breast cancer, glioblastoma and pancreas cancer. We also explore its contribution in cell differentiation events during neurogenesis and muscle regeneration. We develop these projects combining biochemistry, cellular approaches and molecular biology with the generation and functional characterization of loss-of-function cellular models (with a particular interest for stem cells) and animal models (Cripsr/Cas 9, knockout mouse models).

Techniques d’étude de l’intégrité du génome et des mécanismes de réparation in vitro (Essais de Poly(ADP-ribosyl)ation), in cellulo (SCE, Essais Comet, Essais Tunel, cinétique des foyers gH2AX, 53BP1, BRCA1, RAD51, poly(ADP-ribose) par immunofluorescence, modèles cellulaires d’évaluation de la réparation) et in vivo (gH2AX, 53BP1, BRCA1, RAD51, poly(ADP-ribose) par immunohistochimie sur coupes de tissus).

 

UMR 7242 CNRS-Unistra, ESBS and Faculty of Pharmacy,
 
300 Boulevard Sébastien Brant 67412 Illkirch

francoise.dantzer (at) unistra.fr

Group leader : Dominique Bonnet

Integrative Chemical Biology

Our team belongs to the Laboratory of Therapeutic Innovation (UMR7200, Faculty of Pharmacy of Illkirch) and is member of the Strasbourg Drug Discovery and Development Institute (IMS), the Pole of Excellence ‘Frontier Research in Chemistry’ and the Graduate School of Pain (EURIDOL).

  • Patented “FluoroPEP” technology1.
The huge therapeutic potential of peptides has not yet been fully exploited mainly due to their short in vivo half-life. Our team has developed an innovative fluorocarbon-peptide conjugation approach to greatly enhance the plasma stability of peptides and their in vivo efficacy2. Figure. Innovative approach to increase plasmatic stability and in vivo efficacy of peptides for therapeutic applications.   References: [1] (a) Esteoulle L.; Simonin F.; Bonnet D. Metabolically stable spexin peptide analogs. WO2017216360; 21-12-2017; (b) Iturrioz X.; Llorens-Cortes C.; Bonnet D. Metabolically stable peptide analogs. WO2017216359; 21-12-2017; (c) Iturrioz, X.; Llorens-Cortes, C.; Bonnet D. Metabolically stable apelin analogs in the treatment of disease mediated by the apelin receptor. WO2016/102648, 30-06-2016. [2] (a) Flahault, A. et al. NatCommun., 2021, 12, 1-14; (b) Jourdain de Muizo, C. et al. ChemBioChem, 2020, 1-6; (c) Gerbier, R. et al. FASEB J., 2017, 31, 687-700.
  • Patented “Turn-ON” technology1.
Fluorogenic probes, which turn on their fluorescence in response to a target, have attracted considerable attention as new tools for molecular sensing in biology. Our team, in collaboration with A. Klymchenko (LBP, UMR7173, Illkirch), has designed an innovative strategy so called “Turn-ON” technology for receptor imaging both in living cells2 and whole organism3 in physiological conditions (Figure). Figure. New concept of fluorogenic dimer ligands for the background-free fluorescence imaging of GPCR.   References: [1] Karpenko, I.; Collot, M.; Klymchenko, A.; Bonnet, D. EP20305479.6, 12-05-2020 [2] Karpenko, I.A. et al. J. Am. Chem. Soc., 2015, 137, 405-412. [3] Esteoulle, L. et al. Chem. Sci. 2020, 11, 6824-6829.
UMR 7200 CNRS-Unistra, Faculté de pharmacie
74 route du Rhin – CS 60024 – 67401 Illkirch Cedex

dominique.bonnet (at) unistra.fr

Group leader : Alain Wagner

BioFunctional Chemistry

We are primarily developing our research along three directions:
Bio-specific chemical reactions: for precise stoichiometric conjugation and controlled delivery of drugs or payloads. Control of conjugation stoichiometry opens prospects toward novel format of hybrid bimolecular constructs for drug delivery or biophysical studies.
In vivo chemistry: to uncover the rules that guide chemical reactions in complex biofluids taking into account reagent transport, bio-distribution and pharmacokinetics. It opens new opportunities toward alternative therapeutic and chemo-omics approaches via in vivo modification of biotics (metabolites) or xenobiotics (drugs, imaging agents).
Single Cell Omic: by developing novel biomolecule capture system and phase inversion microfluidic technologies we paved the way toward advanced single cell multi-omic approaches (transcriptomic, proteomic, secretomic, surfacomic). This technology provides a unique insight into cancer heterogeneity and differentiation processes.

UMR 7199 CNRS-Unistra, Laboratoire de Conception et Application de Molécules Bioactives

Faculté de pharmacie, 74 route du Rhin, 67401 Illkirch Cedex

alwag (at) unistra.fr