|Academic Profile |
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Prof Marie-Paule Teulade-Fichou
Visiting Professor, School of Physical & Mathematical Sciences
Office: ADM D01 00
|Dr. M.P Teulade-Fichou is a Research Director (1st Class) at CNRS. She was originally educated in Biochemistry and Pharmacology at University Denis Diderot (ParisVII) working on analogues of Platelet Activating Factor (“3eme cycle” doctorate in Pharmaceutical Chemistry in 1984 under the guidance of Prof. Jean-Jacques Godefroid) and then graduated in Chemistry at the University Pierre & Marie Curie (Paris VI) working on new methodology for phosphorus-carbon bond formation (PhD Doctorate in Organic Chemistry in 1986 under the guidance of Dr. P. Savignac). She then took up a position at CNRS in 1986, to develop research on organophosphorus compounds in the laboratory of Phosphorus Chemistry headed by Prof. François Mathey at the Ecole Polytechnique. In 1991 she joined the group of Prof. Jean-Marie Lehn in Paris (Laboratory of Chemistry of Molecular Interactions, College de France) where she developed macrocylic chemistry for recognition of nucleic acids. In parallel she started targeting higher order DNA helices ( triplexes, quadruplexes) with small molecules in close collaboration with the group of Prof. Claude Hélène and in particular the team of Dr. Jean-Louis Mergny. In 2007 she moved to the Institut Curie where she was subsequently deputy director and director of the Chemistry research unit (CNRS-UMR176). Since January 2015 she is head of the newly created research unit Chemistry, Modelling and Imaging for Biology (CMIB) (CNRS-UMR9187 / INSERM-U1196). Dr. M.-P. Teulade-Fichou is team-leader of the group “Structure and Fluorescence Probes for Nucleic Acids”, she has published > 170 articles in the field of organic chemistry and bioorganic chemistry of nucleic acids and she is co-inventor of 6 patents.|
Dr. Teulade-Fichou was awarded the CNRS Silver medal in 2015. This distinction honors mid-career/ senior scientists who are recognized nationally and internationally for the originality, quality and importance of their work. One to four laureates are awarded each year per field of research (Chemistry, Physics, Biology, Mathematics, Human Sciences etc..).
She was awarded “Chevalier de la Légion d’Honneur” in 2016 , the highest French Order of merit.
|Our current interest is focused on the design of new nucleic acid targeted compounds for anticancer research and for elucidating DNA-related molecular basis of cancer.|
It is well recognized that DNA sequences containing repeats of heterocyclic bases are highly susceptible to aberrant replication and perturbation of other DNA-related processes such as recombination and transcription. These dysfunctions may lead ultimately to modifications of the genetic material) and may have a role in explaining mechanisms linked to cancer development or more largely be involved in pathogenic rearrangements genome-wide. Repeat-containing DNA domains are highly prone to form non-canonical secondary structures due to self-assembly of bases via various H-bonding modes ( mismatched base-pairs, base-triplets or quartets). The generated structures (hairpins, mismatched sites, triplex, quadruplex) are known (for some) or suspected (for others) to be involved in genetic instability and in pathogenic dysfunctions.
Our team is interested in the recognition of these non-canonical structures locally formed in DNA by means of specifically designed small molecules (i.e. ligands) that will bind the target structure with high specificity. The primary objectives of this research are two-folded, firstly to provide structure probes usable in various in vitro and cellular models for exploring the polymorphism of DNA; secondly to provide functional probes reporting or acting on the target structure (fluorescent signalling, covalent crosslinking). Of note the design and synthesis of targeted fluorescent molecules compatible with cellular imaging represent a subtopic of our research tightly intertwined with the structure targeting topic. The final objectives of this research are to create new chemical biology tools for studying and controlling the formation of the target structures as well as their processing by proteins. Ultimately we aim at the discovery of better targeted (regiospecific) DNA interactive agents that may become clinical drugs for anticancer chemotherapy.
Our specific approaches towards the identification of active scaffolds are based on rational design (shape complementarity- topology adaptation) and on screening methods. Thus we developed home-made assays amenable to high throughput screening. These are combined with the use of state of the art optical spectroscopy (UV-Vis, fluorescence, circular dichroïsm) and biochemical methods (gel electrophoresis, pull down assay) for quantitative evaluation of NA-ligands interactions. We also intend to a deep understanding of non-covalent interactions at the atomic level by means of molecular modelling analyses. Our research has led to the development of several original chemical series , mainly polyheterocycles and transition metal (Pt, Pd, Cu) complexes. In particular we developed the bisquinolinium phenanthroline derivative PhenDC3 currently used as quadruplex benchmark probe worldwide.
We are also contributing to two translational projects in collaboration with clinicians of the Institut Curie i) Optimized phtosensitizers for Photodynamic treatment of retinoblastoma and ii) New radiosensitizers for treating radioresistant cancers ( Glioblatoma).
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