Publications

Publications
Mitochondrial protein sorting as a therapeutic target for ATP synthase disorders.
Nature communications

 Aiyar RS, Bohnert M, Duvezin-Caubet S, Voisset C, Gagneur J, Fritsch ES, Couplan E, von der Malsburg K, Funaya C, Soubigou F, Courtin F, Suresh S, Kucharczyk R, Evrard J, Antony C, St Onge RP, Blondel M, di Rago J, van der Laan M, Steinmetz LM
 Nature communications - vol. 5 1-9 (2014)

Mitochondrial diseases are systemic, prevalent and often fatal; yet treatments remain scarce. Identifying molecular intervention points that can be therapeutically targeted remains a major challenge, which we confronted via a screening assay we developed. Using yeast models of mitochondrial ATP synthase disorders, we screened a drug repurposing library, and applied genomic and biochemical techniques to […]

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
A screening cascade to identify ERβ ligands
Nuclear Receptor Signaling

 Filgueira CS, Benod C, Lou X, Gunamalai PS, Villagomez RA, Strom A, Gustafsson J, Berkenstam AL, Webb P
 Nuclear Receptor Signaling - vol. 12 1-13 (2014)

The establishment of effective high throughput screening cascades to identify nuclear receptor (NR) ligands that will trigger defined, therapeutically useful sets of NR activities is of considerable importance. Repositioning of existing approved drugs with known side effect profiles can provide advantages because de novo drug design suffers from high developmental failure rates and undesirable side […]

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 […]

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