Publications related to From Patients to Platelets and Back Again: Pharmacological Approaches to Glycoprotein VI, a Thrilling Antithrombotic Target with Minor Bleeding Risks

MRI characterization of in vitro clots at 3T and 7T: A technical note

In acute ischemic stroke, the composition of the occlusive clot can be associated with the underlying pathophysiology and the response to treatment. For these reasons, it is important to characterize the clot composition from clinical scans. We examine the ...

Masson Editeur2024

A locally activatable sensor for robust quantification of organellar glutathione

Pablo Rivera Fuentes, Sarah Emmert, Gianluca Quargnali

Glutathione (GSH) is the main determinant of intracellular redox potential and participates in multiple cellular signalling pathways. Achieving a detailed understanding of intracellular GSH homeostasis depends on the development of tools to map GSH compart ...

NATURE PORTFOLIO2023

Unlocking Hidden Potential: Exploring the Complexities of Signaling in Immune Cell Activation to Optimize CAR Therapy

Mathieu Girardin

Chimeric antigen receptors (CARs) are synthetic, transmembrane proteins that trigger immune cell signaling following their engagement. They have been first utilized in T cells and later in natural killer (NK) cells to redirect their cytotoxicity toward a s ...

EPFL2023

Towards Uncovering the Mechanisms of Electrophile Sensing and Signaling

Chloé Rogg

Native reactive electrophile species (RES) such as 4-hydroxynonenal (HNE) act as cellular signals through covalent modification of kinetically-privileged electrophile sensor proteins. Research efforts in the field focus mainly on identifying these sensor p ...

EPFL2023

Impact of atrial fibrillation on left atrium haemodynamics: A computational fluid dynamics study

Alfio Quarteroni, Luca Dede'

We analyse the haemodynamics of the left atrium, highlighting differences between healthy individuals and patients affected by atrial fibrillation. The computational study is based on patient-specific geometries of the left atria to simulate blood flow dyn ...

PERGAMON-ELSEVIER SCIENCE LTD2022

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

Pleiotropic effects of mitochondria in aging

Johan Auwerx, Adrienne Joëlle Laurence Mottis, Yang Li, Tanes Imamura de Lima

Aging is typified by a progressive decline in mitochondrial activity and stress resilience. Here, we review how mitochondrial stress pathways have pleiotropic effects on cellular and systemic homeostasis, which can comprise protective or detrimental respon ...

SPRINGERNATURE2022

Evolutionary history expands the range of signaling interactions in hybrid multikinase networks

Mohamed Barakat, Anne-Florence Raphaëlle Bitbol

Two-component systems (TCSs) are ubiquitous signaling pathways, typically comprising a sensory histidine kinase (HK) and a response regulator, which communicate via intermolecular kinase-to-receiver domain phosphotransfer. Hybrid HKs constitute non-canonic ...

NATURE RESEARCH2021

Cyclic peptide FXII inhibitor provides safe anticoagulation in a thrombosis model and in artificial lungs

Christian Heinis, Jonas Alfred Karl Wilbs, Simon Jan Middendorp, Xudong Kong, Christina Lamers, Patrick Andreas Gonschorek

Inhibiting thrombosis without generating bleeding risks is a major challenge in medicine. A promising solution may be the inhibition of coagulation factor XII (FXII), because its knock-out or inhibition in animals reduced thrombosis without causing abnorma ...

Nature Research2020

De novo development of proteolytically resistant therapeutic peptides for oral administration

Christian Heinis, Florence Pojer, Luciano Andres Abriata, Xudong Kong, Kaycie Marie Butler, Vanessa Carle, Jun Moriya

The oral administration of peptide drugs is hampered by their metabolic instability and limited intestinal uptake. Here, we describe a method for the generation of small target-specific peptides (less than 1,600 Da in size) that resist gastrointestinal pro ...

2020

Modeling metabolic and signaling pathways in cancer cells

Maria Masid Barcon

Cancer is a leading cause of death in the world, and the mechanisms that underlie this disease are still not completely understood. As cancer develops and progresses, cells undergo a diversity of mutations that sustain their rapid proliferation and the eva ...

EPFL2020

Multi-color Molecular Visualization of Signaling Proteins Reveals How C-Terminal Src Kinase Nanoclusters Regulate T Cell Receptor Activation

Juliette Griffie

Elucidating the mechanisms that controlled T cell activation requires visualization of the spatial organization of multiple proteins on the submicron scale. Here, we use stoichiometrically accurate, multiplexed, single-molecule super-resolution microscopy ...

CELL PRESS2020

REX technologies for profiling and decoding the electrophile signaling axes mediated by Rosetta Stone proteins

Yimon Aye, Daniel Ahmet Urul

It is now clear that some cysteines on some proteins are highly tuned to react with electrophiles. Based on numerous studies, it is also established that electrophile sensing underpins rewiring of several critical signaling processes. These electrophile-se ...

ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD2020

Development of cyclic peptide inhibitors of coagulation factor XIa for safer anticoagulation

Vanessa Carle

Hemostasis is a complex physiological process responsible for the prevention of blood loss caused by vascular injury. The dysregulation of this delicate mechanism can lead to thromboembolic diseases, the leading cause of death worldwide. Anticoagulants are ...

EPFL2019

An optimized and validated 384-well plate assay to test platelet function in a high-throughput screening format

Nikolaos Stergiopoulos, Marc Chambon, Olivier Burri, Rodrigo Araujo Fraga Da Silva, Fabiana Pereira Da Costa Fraga, Julien Bortoli Chapalay, Maiia Bragina, Augusto Martins Lima

Despite significant advances in the treatment of cardiovascular diseases, antiplatelet therapies are still associated with a high risk of hemorrhage. In order to develop new drugs, methods to measure platelet function must be adapted for the high-throughpu ...

TAYLOR & FRANCIS INC2019

The heparin binding domain of von Willebrand factor binds to growth factors and promotes angiogenesis in wound healing

Matthias Lütolf, Jeffrey Alan Hubbell, Yoji Tabata, Jun Ishihara, Kazuto Fukunaga

During wound healing, the distribution, availability, and signaling of growth factors (GFs) are orchestrated by their binding to extracellular matrix components in the wound microenvironment. Extracellular matrix proteins have been shown to modulate angiog ...

AMER SOC HEMATOLOGY2019

Quantitative relationships between SMAD dynamics and target gene activation kinetics in single live cells

Felix Naef, Onur Tidin, David Michael Suter, Torgil Elias Friman

The transduction of extracellular signals through signaling pathways that culminate in a transcriptional response is central to many biological processes. However, quantitative relationships between activities of signaling pathway components and transcript ...

Nature Research2019

Development of cyclic peptide inhibitors of coagulation factor XII and matrix metalloproteinase 2

Jonas Alfred Karl Wilbs

Peptides represent a promising molecular class for drug development. They combine several strengths of small molecules (e.g. efficient tissue diffusion, low immunogenicity and access to chemical synthesis) and key properties of biologics such as monoclonal ...

EPFL2018

Efficient transdifferentiation of human dermal fibroblasts into skeletal muscle

Noaf Salah Ali Alwahab

Skeletal muscle holds significant regenerative potential but is incapable of restoring tissue loss caused by severe injury, congenital defects or tumour ablation. Consequently, skeletal muscle models are being developed to study human pathophysiology and r ...

WILEY2018

Risk prediction of developing venous thrombosis in combined oral contraceptive users

Emmanuelle Logette, Valérie Buchillier

Background Venous thromboembolism (VTE) is a complex multifactorial disease influenced by genetic and environmental risk factors. An example for the latter is the regular use of combined oral contraceptives (CC), which increases the risk to develop VTE by ...

2017