Publications related to Monitoring On-Target Signaling Responses in Larval Zebrafish- Z-REX Unmasks Precise Mechanisms of Electrophilic Drugs and Metabolites

HaloTag-Based Tools for Live-Cell Imaging and Elucidation of Organellar Redox Biology

Redox homeostasis is a key factor in maintaining cellular function and health. The main determinant of the intracellular redox potential is ubiquitous glutathione (GSH) together with its oxidized dimer (GSSG). Importantly, both redox equilibrium and GSH ho ...

EPFL2024

Adolescent Stress-Induced Ventral Hippocampus Redox Dysregulation Underlies Behavioral Deficits and Excitatory/Inhibitory Imbalance Related to Schizophrenia

Maria del Carmen Sandi Perez, Dogukan Hazar Ülgen, Thamyris Silva

Background and hypothesis: Redox dysregulation has been proposed as a convergent point of childhood trauma and the emergence of psychiatric disorders, such as schizophrenia (SCZ). A critical region particularly vulnerable to environmental insults during ad ...

2024

Primary data for "A role for the carbon source of the cell and protein kinase A in regulating the S. pombe septation initiation network"

Bastien Mangeat, Viesturs Simanis, Andrea Krapp, Özge Uysal Özdemir

The Septation Initiation Network (SIN) is a conserved signal transduction network, which is important for cytokinesis in S. pombe. The SIN component Etd1p is required for association of some SIN proteins with the spindle pole body (SPB) during anaphase and ...

EPFL Infoscience2024

A role for the carbon source of the cell and protein kinase A in regulating the S. pombe septation initiation network

Bastien Mangeat, Viesturs Simanis, Andrea Krapp, Özge Uysal Özdemir

The septation initiation network (SIN) is a conserved signal transduction network, which is important for cytokinesis in Schizosaccharomyces pombe. The SIN component Etd1p is required for association of some SIN proteins with the spindle pole body (SPB) du ...

2024

Hitting the Bullseye: Endogenous Electrophiles Show Remarkable Nuance in Signaling Regulation

Yimon Aye, Pierre Alexander Miranda Herrera

Our bodies produce a host of electrophilic species that can label specific endogenous proteins in cells. The signaling roles of these molecules are under active debate. However, in our opinion, it is becoming increasingly likely that electrophiles can rewi ...

AMER CHEMICAL SOC2022

Metabolic regulation of cytokinesis in Schizosaccharomyces pombe

Özge Uysal Özdemir

All cells need to be able to sense their environment, and adapt their metabolism, growth and cell division appropriately. In this study, I examined the response of Schizosaccharomyces pombe to a change in the carbon source and how that affects cytokinesis. ...

EPFL2022

Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis

Didier Trono, Laurence Gouzi Abrami, Julien Léonard Duc, Sandra Eloise Kjeldsen, Alexandre Coudray, Sagane Dind, Evaristo Jose Planet Letschert, Laia Simo Riudalbas

The treatment of colorectal cancer (CRC) is an unmet medical need in absence of early diagnosis. Here, upon characterizing cancer-specific transposable element-driven transpochimeric gene transcripts (TcGTs) produced by this tumor in the SYSCOL cohort, we ...

Nature Research2022

Photochemical oxidation of phenols and anilines mediated by phenoxyl radicals in aqueous solution

Silvio Canonica, Urs von Gunten, Stephanie Christa Remke

Reactive intermediates formed upon irradiation of chromophoric dissolved organic matter (CDOM) contribute to the degradation of various organic contaminants in surface waters. Besides well-studied "short-lived" photo oxidants, such as triplet state CDOM (3 ...

PERGAMON-ELSEVIER SCIENCE LTD2022

Intrinsically High Capacity of Animal Cells From a Symbiotic Cnidarian to Deal With Pro-Oxidative Conditions

Gaëlle Delphine Toullec

The cnidarian-dinoflagellate symbiosis is a mutualistic intracellular association based on the photosynthetic activity of the endosymbiont. This relationship involves significant constraints and requires co-evolution processes, such as an extensive capacit ...

FRONTIERS MEDIA SA2022

An Oculus to Profile and Probe Target Engagement In Vivo: How T-REX Was Born and Its Evolution into G-REX

Chloé Rogg, Yimon Aye

Here we provide a personal account of innovation and design principles underpinning a method to interrogate precision electrophile signaling that has come to be known as "REX technologies". This Account is framed in the context of trying to improve methods ...

AMER CHEMICAL SOC2021

Method Development towards Orthogonal Electrophile Delivery

Lingxi Wang

Redox signaling events mediated by reactive electrophilic species (RES) are key players in several cellular processes. However, the studies on RES have been challenging due to their high reactivity towards numerous nucleophilic groups present in the cells ...

EPFL2021

Can Precision Electrophile Signaling Make a Meaningful and Lasting Impression in Drug Design?

Yimon Aye, Amogh Kulkarni

For several years, drugs with reactive electrophilic appendages have been developed. These units typically confer prolonged residence time of the drugs on their protein targets, and may assist targeting shallow binding sites and/or improving the drug-prote ...

WILEY-V C H VERLAG GMBH2022

Renal Purge of Hemolymphatic Lipids Prevents the Accumulation of ROS-Induced Inflammatory Oxidized Lipids and Protects Drosophila from Tissue Damage

Bruno Lemaitre, Samuel Rommelaere, Xiaoxue Li

Animals require complex metabolic and physiological adaptations to maintain the function of vital organs in response to environmental stresses and infection. Here, we found that infection or injury in Drosophila induced the excretion of hemolymphatic lipid ...

2020

Reactions of nitrogen-containing compounds with ozone: kinetics and mechanisms

Sung Eun Lim

Nitrogen-containing moieties are widespread in natural waters in dissolved organic nitrogen and micropollu-tants. They are often susceptible to an electrophilic attack of ozone because of the electron-rich nature of the neutral form of nitrogen in organic ...

EPFL2020

Precision Targeting of pten-Null Triple-Negative Breast Tumors Guided by Electrophilic Metabolite Sensing

Yimon Aye, Xuyu Liu, Lingxi Wang, Chaosheng Luo

Off-target effects continue to impede disease interventions, particularly when targeting a specific protein within a family of similar proteins, such as kinase isoforms that play tumor-subtype-specific roles in cancers. Exploiting the specific electrophili ...

AMER CHEMICAL SOC2020

Biotransformation Capacity of Zebrafish (Danio rerio) Early Life Stages: Functionality of the Mercapturic Acid Pathway

Kristin Schirmer, Alena Tierbach

Zebrafish (Danio rerio) early life stages offer a versatile model system to study the efficacy and safety of drugs or other chemicals with regard to human and environmental health. This is because, aside from the well-characterized genome of zebrafish and ...

OXFORD UNIV PRESS2020

Neighborhood watch: tools for defining locale-dependent subproteomes and their contextual signaling activities

Yimon Aye, Yi Zhao

Transient associations between numerous organelles-e.g., the endoplasmic reticulum and the mitochondria-forge highly-coordinated, particular environments essential for cross-compartment information flow. Our perspective summarizes chemical-biology tools th ...

ROYAL SOC CHEMISTRY2020

Receptor-independent modulation of cAMP-dependent protein kinase and protein phosphatase signaling in cardiac myocytes by oxidizing agents

Sonia Donzelli

The contraction and relaxation of the heart is controlled by stimulation of the beta 1-adrenoreceptor (AR) signaling cascade, which leads to activation of cAMP-dependent protein kinase (PKA) and subsequent cardiac protein phosphorylation. Phosphorylation i ...

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC2020

Getting the Right Grip? How Understanding Electrophile Selectivity Profiles Could Illuminate Our Understanding of Redox Signaling

Yimon Aye, Lingxi Wang

Recent Advances: Herein, we focus on the first step of this process, electrophile sensing. Electrophile sensing is typically a deceptively simple reaction between the thiol of a protein cysteine, of which there are around 200,000 in the human proteome, and ...

MARY ANN LIEBERT, INC2020

Proteomics and Beyond: Cell Decision-Making Shaped by Reactive Electrophiles

Yimon Aye, Xuyu Liu

Revolutionary proteomic strategies have enabled rapid profiling of the cellular targets of electrophilic small molecules. However, precise means to directly interrogate how these individual electrophilic modifications at low occupancy functionally reshape ...

2019