Shiri Zakin

Accelerating Leigh syndrome drug discovery through deep learning screening in brain organoids

Carmen Menacho, Satoshi Okawa, Iris Álvarez‐Merz, Annika Wittich et autres

Leigh syndrome (Leigh) is an untreatable mitochondrial disorder characterized by lactic acidosis and basal ganglia and midbrain pathology, leading to psychomotor regression and early death. We previously uncovered impaired neuronal morphogenesis in Leigh cerebral organoids carrying SURF1 gene variants. Leveraging this phenotype, …

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Accelerating Leigh syndrome drug discovery through deep learning screening in brain organoids

Carmen Menacho, Satoshi Okawa, Iris Álvarez‐Merz, Annika Wittich et autres

Leigh syndrome (Leigh) is an untreatable mitochondrial disorder characterized by lactic acidosis and basal ganglia and midbrain pathology, leading to psychomotor regression and early death. We previously uncovered impaired neuronal morphogenesis in Leigh cerebral organoids carrying SURF1 gene variants. Leveraging this phenotype, …

Industrializing yeast as a drug repurposing platform for inherited metabolic diseases

Mathuravani A. Thevandavakkam, Natalie E. Long, Briannna M. Roel, Kristin A. Kantautas et autres

Summary The development of therapies for rare diseases, particularly inherited metabolic disorders (IMDs), faces significant challenges due to the high cost and lengthy timelines involved. This study presents a yeast-based platform for drug repurposing that capitalizes on the remarkable similarity between yeast …

Deep learning-driven neuromorphogenesis screenings identify repurposable drugs for mitochondrial disease

Carmen Menacho, Satoshi Okawa, Iris Álvarez‐Merz, Annika Wittich et autres

Summary Mitochondrial disease encompasses untreatable conditions affecting tissues with high energy demands. A severe manifestation of mitochondrial disease is Leigh syndrome (Leigh), which causes defects in basal ganglia and midbrain regions, psychomotor regression, lactic acidosis, and early death. We previously generated isogenic …

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Antifungal tolerance is a subpopulation effect distinct from resistance and is associated with persistent candidemia

Alexander Jacob Rosenberg, Iuliana V. Ene, Maayan Bibi, Shiri Zakin et autres

Tolerance to antifungal drug concentrations above the minimal inhibitory concentration (MIC) is rarely quantified, and current clinical recommendations suggest it should be ignored. Here, we quantify antifungal tolerance in Candida albicans isolates as the fraction of growth above the MIC, and find …

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Clearing the FoG: Antifungal tolerance is a subpopulation effect that is distinct from resistance and is associated with persistent candidemia

Alexander Jacob Rosenberg, Iuliana V. Ene, Maayan Bibi, Shiri Zakin et autres

Abstract Drug susceptibility, defined by the minimal inhibitory concentration (MIC), often does not predict whether fungal infections will respond to therapy in the clinic. Tolerance at supra-MIC antifungal drug concentrations is rarely quantified and current clinical recommendations suggest it be ignored. Here, …

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Multidrug-Resistant Candida haemulonii and C. auris , Tel Aviv, Israel

Ronen Ben‐Ami, Judith G. Berman, Ana Novikov, Edna Bash et autres

Candida auris and C. haemulonii are closely related, multidrug-resistant emerging fungal pathogens that are not readily distinguishable with phenotypic assays. We studied C. auris and C. haemulonii clinical isolates from 2 hospitals in central Israel. C. auris was isolated in 5 patients …

Candida haemulonii and Candida auris: Emerging Multidrug-Resistant Species With Distinct Virulence and Epidemiological Characteristics

Talya Finn, Anna Novikov, Shiri Zakin, Edna Bash et autres

Background. Candida haemulonii and Candida auris are recently described, closely related drug-resistant Candida species. Little is known about the pathogenicity and epidemiological characteristics of these species. Methods. We reviewed Candida clinical isolates recovered from January 2008 through December 2015 at the Tel …

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