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Success Stories


Publications
A small molecule screen identifies an inhibitor of DNA repair inducing the degradation of TFIIH and the Chemosensitization of tumor cells to platinum

Chemistry and Biology

Alekseev S, Ayadi M, Brino L, Egly JM, Larsen AK, Coin F
Chemistry and Biology - vol. 21 398-407 (2014)

Nucleotide excision repair (NER) removes DNA lesions resulting from exposure to UV irradiation or chemical agents such as platinum-based drugs used as anticancer molecules. Pharmacological inhibition of NER is expected to enhance chemosensitivity but nontoxic NER inhibitors are rare. Using a drug repositioning approach, we identify spironolactone (SP), an antagonist of aldosterone, as a potent […]

Publications
A method to identify and validate mitochondrial modulators using mammalian cells and the worm C. elegans.

Scientific reports

Andreux PA, Mouchiroud L, Wang X, Jovaisaite V, Mottis A, Bichet S, Moullan N, Houtkooper RH, Auwerx J
Scientific reports - vol. 4 1-10 (2014)

Mitochondria are semi-autonomous organelles regulated by a complex network of proteins that are vital for many cellular functions. Because mitochondrial modulators can impact many aspects of cellular homeostasis, their identification and validation has proven challenging. It requires the measurement of multiple parameters in parallel to understand the exact nature of the changes induced by such […]

Publications
Boosting innate immunity: Development and validation of a cell-based screening assay to identify LL-37 inducers.

Innate immunity

Nylén F, Miraglia E, Cederlund A, Ottosson H, Strömberg R, Gudmundsson GH, Agerberth B
Innate immunity - vol. 20 364-376 (2014)

Innate immunity, the front line of our defence against pathogens, relies, to a great extent, on the production of antimicrobial peptides (AMPs). These peptides exhibit antimicrobial activity and immunomodulatory properties. In humans, AMPs include the defensins (α- and β-families) and the cathelicidin, LL-37. Bacterial resistance against antibiotics is a growing concern, and novel antimicrobial strategies […]

Publications
Using yeast to model calcium-related diseases: Example of the Hailey-Hailey disease

Biochimica et Biophysica Acta - Molecular Cell Research

Voisset C, García-Rodríguez N, Birkmire A, Blondel M, Wellinger RE
Biochimica et Biophysica Acta - Molecular Cell Research - vol. 1843 2315-2321 (2014)

Cross-complementation studies offer the possibility to overcome limitations imposed by the inherent complexity of multicellular organisms in the study of human diseases, by taking advantage of simpler model organisms like the budding yeast Saccharomyces cerevisiae. This review deals with, (1) the use of S. cerevisiae as a model organism to study human diseases, (2) yeast-based […]

Publications
Development of a high-throughput screening cancer cell-based luciferase refolding assay for identifying Hsp90 inhibitors.

Assay and drug development technologies

Sadikot T, Swink M, Eskew JD, Brown D, Zhao H, Kusuma BR, Rajewski RA, Blagg BSJ, Matts RL, Holzbeierlein JM, Vielhauer GA
Assay and drug development technologies - vol. 11 478-488 (2013)

The 90 kDa heat-shock protein (Hsp90) and other cochaperones allow for proper folding of nascent or misfolded polypeptides. Cancer cells exploit these chaperones by maintaining the stability of mutated and misfolded oncoproteins and allowing them to evade proteosomal degradation. Inhibiting Hsp90 is an attractive strategy for cancer therapy, as the concomitant degradation of multiple oncoproteins […]

Publications
High-throughput screening of a collection of known pharmacologically active small compounds for identification of candida albicans biofilm inhibitors

Antimicrobial Agents and Chemotherapy

Siles SA, Srinivasan A, Pierce CG, Lopez-Ribot JL, Ramasubramanian AK
Antimicrobial Agents and Chemotherapy - vol. 57 3681-3687 (2013)

Candida albicans is the most common etiologic agent of systemic fungal infections with unacceptably high mortality rates. The existing arsenal of antifungal drugs is very limited and is particularly ineffective against C. albicans biofilms. To address the unmet need for novel antifungals, particularly those active against biofilms, we have screened a small molecule library consisting […]

Publications
Metformin impairs glucose consumption and survival in Calu-1 cells by direct inhibition of hexokinase-II.

Scientific reports

Salani B, Marini C, Rio AD, Ravera S, Massollo M, Orengo AM, Amaro A, Passalacqua M, Maffioli S, Pfeffer U, Cordera R, Maggi D, Sambuceti G
Scientific reports - vol. 3 1-8 (2013)

The anti-hyperglycaemic drug metformin has important anticancer properties as shown by the direct inhibition of cancer cells proliferation. Tumor cells avidly use glucose as a source for energy production and cell building blocks. Critical to this phenotype is the production of glucose-6-phosphate (G6P), catalysed by hexokinases (HK) I and II, whose role in glucose retention […]

Publications
Luteolin is a novel p90 ribosomal S6 kinase (RSK) inhibitor that suppresses Notch4 signaling by blocking the activation of Y-box binding protein-1 (YB-1).

Oncotarget

Reipas KM, Law JH, Couto N, Islam S, Li Y, Li H, Cherkasov A, Jung K, Cheema AS, Jones SJM, Hassell JA, Dunn SE
Oncotarget - vol. 4 329-345 (2013)

Triple-negative breast cancers (TNBC) are notoriously difficult to treat because they lack hormone receptors and have limited targeted therapies. Recently, we demonstrated that p90 ribosomal S6 kinase (RSK) is essential for TNBC growth and survival indicating it as a target for therapeutic development. RSK phosphorylates Y-box binding protein-1 (YB-1), an oncogenic transcription/translation factor, highly expressed […]

Publications
Novel surface-based methodologies for investigating GH11 xylanase-lignin derivative interactions.

The Analyst

Zeder-Lutz G, Renau-Ferrer S, Aguié-Béghin V, Rakotoarivonina H, Chabbert B, Altschuh D, Rémond C
The Analyst - vol. 138 6889-99 (2013)

The recalcitrance of lignocellulose to bioprocessing represents the core problem and remains the limiting factor in creating an economy based on lignocellulosic ethanol production. Lignin is responsible for unproductive interactions with enzymes, and understanding how lignin impairs the susceptibility of biomass to enzymatic hydrolysis represents a significant aim in optimising the biological deconstruction of lignocellulose. […]

Publications
Synergy of the antibiotic colistin with echinocandin antifungals in candida species

Journal of Antimicrobial Chemotherapy

Zeidler U, Bougnoux ME, Lupan A, Helynck O, Doyen A, Garcia Z, Sertour N, Clavaud C, Munier-Lehmann H, Saveanu C, d'Enfert C
Journal of Antimicrobial Chemotherapy - vol. 68 1285-1296 (2013)

OBJECTIVES: Candida albicans is the most prevalent fungal pathogen of humans, causing a wide range of infections from harmless superficial to severe systemic infections. Improvement of the antifungal arsenal is needed since existing antifungals can be associated with limited efficacy, toxicity and antifungal resistance. Here we aimed to identify compounds that act synergistically with echinocandin […]