Publications

Publications
The Action of Physiological and Synthetic Steroids on the Calcium Channel CatSper in Human Sperm
The sperm-specific channel CatSper (cation channel of sperm) controls the intracellular Ca2+ concentration ([Ca2+]i) and plays an essential role in sperm function

 Wehrli, L.; Galdadas, I.; Voirol, L.; Smieško, M.; Cambet, Y.; Jaquet, V.; Guerrier, S.; Gervasio, F. L.; Nef, S.; Rahban, R.
 Front Cell Dev Biol 11, 1221578 (2023)

It is mainly activated by the steroid progesterone (P4) but is also promiscuously activated by a wide range of synthetic and physiological compounds. These compounds include diverse steroids whose action on the channel is so far still controversial. To investigate the effect of these compounds on CatSper and sperm function, we developed a high-throughput screening […]

Publications
Non-Steroidal Estrogens Inhibit Influenza Virus by Interacting with Hemagglutinin and Preventing Viral Fusion
Influenza virus is one of the main causes of respiratory infections worldwide

 Franzi, E.; Mathez, G.; Dinant, S.; Deloizy, C.; Kaiser, L.; Tapparel, C.; Le Goffic, R.; Cagno, V.
 International Journal of Molecular Sciences 24 (20), 15382 (2023)

Despite the availability of seasonal vaccines and antivirals, influenza virus infections cause an important health and economic burden. Therefore, the need to identify alternative antiviral strategies persists. In this study, we identified non-steroidal estrogens as potent inhibitors of influenza virus due to their interaction with the hemagglutinin protein, preventing viral entry. This activity is maintained […]

Publications
Phenotypic Screening Platform Identifies Statins as Enhancers of Immune Cell-Induced Cancer Cell Death
High-throughput screening (HTS) of small molecule drug libraries has greatly facilitated the discovery of new cancer drugs

 Selvin, T.; Berglund, M.; Lenhammar, L.; Jarvius, M.; Nygren, P.; Fryknäs, M.; Larsson, R.; Andersson, C. R.
 BMC Cancer 23 (1), 164 (2023)

However, most phenotypic screening platforms used in the field of oncology are based solely on cancer cell populations and do not allow for the identification of immunomodulatory agents.

Publications
Novel Therapeutic Strategies Targeting UCP2 in Uterine Leiomyosarcoma
Uterine leiomyosarcoma (ULMS) is a malignant stromal tumor arising from the myometrium with a poor prognosis and very limited response to current chemotherapy

 Nagao, Y.; Yokoi, A.; Yoshida, K.; Sugiyama, M.; Watanabe, E.; Nakamura, K.; Kitagawa, M.; Asano-Inami, E.; Koya, Y.; Yoshihara, M.; Tamauchi, S.; Shimizu, Y.; Ikeda, Y.; Yoshikawa, N.; Kato, T.; Yamamoto, Y.; Kajiyama, H.
 Pharmacological Research 189, 106693 (2023)

This study aimed to identify novel targets for ULMS through a three-step screening process using a chemical library consisting of 1271 Food and Drug Administration-approved drugs. First, we evaluated their inhibitory effects on ULMS cells and identified four candidates: proscillaridin A, lanatoside C, floxuridine, and digoxin. Then, we subcutaneously or orthotopically transplanted SK-UT-1 cells into […]

Publications
Preclinical Validation of Repurposable Candidate Drug Compound for Cystic Nephropathies

 Clanget, T.; Heigwer, J.; Pandey, G.; Kraft, P.; Rodenbeck, B.; Mayer, T.; Tabatabaeifar, M.; Gehrig, J.; Westhoff, J.; Korkmaz-Icöz, S.; Schaefer, F.
 Nephrology Dialysis Transplantation 38 (Supplement_1), gfad063c_6189 (2023)

Early-onset cystic kidney disease is a clinically and genetically heterogeneous and overlapping group of rare and often severe disorders with limited, mostly symptomatic treatment options. We developed and utilized inherited polycystic cystic kidney disease (PKD) models to search for pharmacological agents that can rescue or mitigate the disease phenotype.

Publications
Evolution of antibiotic resistance is a world health crisis, fueled by new mutations
Drugs to slow mutagenesis could, as cotherapies, prolong the shelf-life of antibiotics, yet evolution-slowing drugs and drug targets have been underexplored and ineffective

 Zhai, Y.; Pribis, J. P.; Dooling, S. W.; Garcia-Villada, L.; Minnick, P. J.; Xia, J.; Liu, J.; Mei, Q.; Fitzgerald, D. M.; Herman, C.; Hastings, P. J.; (8) Costa-Mattioli, M.; Rosenberg, S. M.
 Science Advances 9 (25), eadg0188 (2023)

Here, we used a network-based strategy to identify drugs that block hubs of fluoroquinolone antibiotic-induced mutagenesis. We identify a U.S. Food and Drug Administration– and European Medicines Agency–approved drug, dequalinium chloride (DEQ), that inhibits activation of the Escherichia coli general stress response, which promotes ciprofloxacin-induced (stress-induced) mutagenic DNA break repair. We uncover the step in […]

Publications
CRISPR/Cas9-Based Screening of FDA-Approved Drugs for NRF2 Activation: A Novel Approach to Discover Therapeutics for Non-Alcoholic Fatty Liver Disease
With the rising prevalence of obesity, non-alcoholic fatty liver disease (NAFLD) now affects 20–25% of the global population

 Li, J.; Arest, S.; Olszowy, B.; Gordon, J.; Barrero, C. A.; Perez-Leal, O.
 Antioxidants 12 (7), 1363 (2023)

NAFLD, a progressive condition associated with oxidative stress, can result in cirrhosis and liver cancer in 10% and 3% of patients suffering NAFLD, respectively. Therapeutic options are currently limited, emphasizing the need for novel treatments. In this study, we examined the potential of activating the transcription factor NRF2, a crucial player in combating oxidative stress, […]

Publications
A Multilevel Screening Pipeline in Zebrafish Identifies Therapeutic Drugs for GAN
Giant axonal neuropathy (GAN) is a fatal neurodegenerative disorder for which there is currently no treatment

 Lescouzères, L.; Hassen‐Khodja, C.; Baudot, A.; Bordignon, B.; Bomont, P.
 EMBO Molecular Medicine e16267 (2023)

Affecting the nervous system, GAN starts in infancy with motor deficits that rapidly evolve toward total loss of ambulation. Using the gan zebrafish model that reproduces the loss of motility as seen in patients, we conducted the first pharmacological screening for the GAN pathology. Here, we established a multilevel pipeline to identify small molecules restoring both the […]

Publications
Leveraging Genetic Diversity to Identify Small Molecules That Reverse Mouse Skeletal Muscle Insulin Resistance
Systems genetics has begun to tackle the complexity of insulin resistance by capitalising on computational advances to study high-diversity populations

 Masson, S. W. C.; Madsen, S.; Cooke, K. C.; Potter, M.; Vegas, A. D.; Carroll, L.; Thillainadesan, S.; Cutler, H. B.; Walder, K. R.; Cooney, G. J.; Morahan, G.; Stöckli, J.; James, D. E.
 Elife RP86961 (2023)

‘Diversity Outbred in Australia (DOz)’ is a population of genetically unique mice with profound metabolic heterogeneity. We leveraged this variance to explore skeletal muscle’s contribution to whole-body insulin action through metabolic phenotyping and skeletal muscle proteomics of 215 DOz mice. Linear modelling identified 553 proteins that associated with whole-body insulin sensitivity (Matsuda Index) including regulators […]

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