Publications associées à Engineered aprotinin for improved stability of fibrin biomaterials

Bacterial matrix metalloproteases and serine proteases contribute to the extra-host inactivation of enteroviruses in lake water

Enteroviruses are ubiquitous contaminants of surface waters, yet their fate in presence of microbial congeners is poorly understood. In this work, we investigated the inactivation of Echovirus-11 (E11) and Coxsackievirus-A9 (CVA9) by bacteria isolated from ...

2022

Human proteinase 3 resistance to inhibition extends to alpha-2 macroglobulin

Marc Moniatte

Polymorphonuclear neutrophils contain at least four serine endopeptidases, namely neutrophil elastase (NE), proteinase 3 (PR3), cathepsin G (CatG), and NSP4, which contribute to the regulation of infection and of inflammatory processes. In physiological co ...

2020

NAD(+) homeostasis in health and disease

Elena Katsyuba, Johan Auwerx, Mario Romani, Dina Hofer

The conceptual evolution of nicotinamide adenine dinucleotide (NAD(+)) from being seen as a simple metabolic cofactor to a pivotal cosubstrate for proteins regulating metabolism and longevity, including the sirtuin family of protein deacylases, has led to ...

2020

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

Novel compartment-specific biosensors reveal a complementary subcellular distribution of bioactive Furin and PC7

Pierpaolo Ginefra

Proprotein Convertases (PCs) constitute a family of serine proteases that activate various hormones, growth factors and cell adhesion molecules by mediating endoproteolytic cleavage of their secreted inactive precursors during their transit in the secret ...

EPFL2018

Modulating NAD(+) metabolism, from bench to bedside

Elena Katsyuba, Johan Auwerx

Discovered in the beginning of the 20(th) century, nicotinamide adenine dinucleotide (NAD(+)) has evolved from a simple oxidoreductase cofactor to being an essential cosubstrate for a wide range of regulatory proteins that include the sirtuin family of NAD ...

Wiley2017

Human Kunitz-type protease inhibitor engineered for enhanced matrix retention extends longevity of fibrin biomaterials

Jeffrey Alan Hubbell, Peter Frey, Kristen Lorentz, Priscilla Suhasna Maithili Briquez, Hans Mattias Larsson

Aprotinin is a broad-spectrum serine protease inhibitor used in the clinic as an anti-fibrinolytic agent in fibrin-based tissue sealants. However, upon re-exposure, some patients suffer from hypersensitivity immune reactions likely related to the bovine or ...

2017

Therapeutic Proteins Engineered for Super-Affinity to the Extracellular Matrix in Regenerative Medicine

Priscilla Suhasna Maithili Briquez

Regenerative medicine aims to repair body tissues when natural mechanisms fail. Growth factors (GFs) are essential proteins that promote tissue regeneration upon injury, and as such, are very promising therapeutic drugs in regenerative medicine. Due to the ...

EPFL2016

NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice

Matthias Lütolf, Ruedi Aebersold, Kristina Schoonjans, Johan Auwerx, Dongryeol Ryu, Hongbo Zhang, Keir Joe Menzies, Karim Laurent Gariani, Xu Wang, Peiling Luan, Davide D'Amico

Adult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to senescence during aging. We demonstrate the importance of the amount of the oxidized form of cellular nicotinamide adenine dinucleotide (NAD(+)) and its imp ...

American Association for the Advancement of Science2016

Dithiol amino acids can structurally shape and enhance the ligand-binding properties of polypeptides

Rudolf Hovius, Christian Heinis, Florence Pojer, Shiyu Chen, Ranganath Gopalakrishnan

The disulfide bonds that form between two cysteine residues are important in defining and rigidifying the structures of proteins and peptides. In polypeptides containing multiple cysteine residues, disulfide isomerization can lead to multiple products with ...

Nature Publishing Group2014

The Nano-Scale Mechanical Properties of the Extracellular Matrix Regulate Dermal Fibroblast Function

Jean-Jacques Meister, Boris Hinz, Josiane Angèle Charlotte Smith-Clerc, Lara Buscemi Estefanell

Changes in the mechanical properties of dermis occur during skin aging or tissue remodeling and affect the activity of resident fibroblasts. With the aim to establish elastic culture substrates that reproduce the variable softness of dermis, we determined ...

Nature Publishing Group2014

Mitonuclear protein imbalance as a conserved longevity mechanism

Graham Knott, Elena Katsyuba, Johan Auwerx, Richardus Houtkooper, Norman Lionel Moullan, Dongryeol Ryu, Laurent Mouchiroud

Longevity is regulated by a network of closely linked metabolic systems. We used a combination of mouse population genetics and RNA interference in Caenorhabditis elegans to identify mitochondrial ribosomal protein S5 (Mrps5) and other mitochondrial riboso ...

Nature Publishing Group2013

Role and regulation of the melanization reaction in Drosophila immune response

Olivier Binggeli

In arthropods, the melanization reaction consists in the rapid synthesis of melanin at the site of infection and injury. A key enzyme in the melanization process is phenoloxidase (PO), which catalyzes the oxidation of phenols to quinones that subsequently ...

EPFL2013

Closing the gap between T-cell life span estimates from stable isotope-labeling studies in mice and humans

Istvan Bartha

Quantitative knowledge of the turnover of different leukocyte populations is a key to our understanding of immune function in health and disease. Much progress has been made thanks to the introduction of stable isotope labeling, the state-of-the-art techni ...

Amer Soc Hematology2013

Biofunctional Scaffold Design for Soft Tissue Regeneration

Kristen Lorentz

Fibrin has long been used clinically for hemostasis and sealing and has been extensively characterized as a biomaterial. Yet, in terms of harnessing its potential for use in tissue regeneration, there remains a wide gap between in vitro experimentation and ...

EPFL2011

SRT1720 improves survival and healthspan of obese mice

Johan Auwerx, Carlos Canto Alvarez

Sirt1 is an NAD1-dependent deacetylase that extends lifespan in lower organisms and improves metabolism and delays the onset of age-related diseases in mammals. Here we show that SRT1720, a synthetic compound that was identified for its ability to activate ...

Nature Publishing Group2011

Tg-aprotinin fusion proteins and matrices thereof

Jeffrey Alan Hubbell, Peter Frey, Kristen Lorentz

Fusion proteins containing a first domain and a second domain, where the first domain contains a crosslinkable substrate domain and the second domain contains a fibrinolysis inhibitor, are provided. In a preferred embodiment, the fibrinolysis inhibitor is ...

2011

It is All About Proteases: From Drug Delivery to In Vivo Imaging and Photomedicine

Hubert van den Bergh

Clinical studies provide overwhelming evidence for the importance of proteolytic imbalance and the upregulation of diverse protease classes in diseases such as cancer and arthritis. While the complex nature of proteolytic networks has hampered the developm ...

Bentham Science Publishers2011

Multi-scale modeling of HIV-1 proteins

Marilisa Neri, Paolo Carloni

The efficiency of protease inhibiting drugs is hampered by the rapid emergence of protease variants. Understanding this phenomenon requires the characterization of the salient steps of HIV-1 protease's catalytic cycle. We summarize Our investigations on th ...

2009

Proteolytic cascade for the activation of the insect toll pathway induced by the fungal cell wall component

Bruno Lemaitre, Ji Won Park

The insect Toll signaling pathway is activated upon recognition of Gram-positive bacteria and fungi, resulting in the expression of antimicrobial peptides via NF-kappaB-like transcription factor. This activation is mediated by a serine protease cascade lea ...

American Society for Biochemistry and Molecular Biology2009