Publications related to The Contorsbody, an antibody format for agonism: design, structure, and function

Androgen Receptor Signaling in in vivo models of Estrogen Receptor-positive Breast Cancer and Normal Breast Epithelium

Steroid hormone receptors (HRs) are ligand-activated transcription factors that play a pivotal role in breast development and carcinogenesis. It is well established that estrogen receptor (ER) signaling is a major proliferative driver in estrogen receptor ...

EPFL2024

From Sequence to Dynamics to Function: Computational Design of Allostery and Ligand Selectivity in G-Protein Coupled Receptors

Mahdi Hijazi

The phenomenon of allostery, a general property in proteins that has been heralded as "the second secret of life" remains elusive to our understanding and even more challenging to incorporate into protein design. One example of allosteric proteins with gre ...

EPFL2024

Proliferation-driven mechanical compression induces signalling centre formation during mammalian organ development

Pengfei Xu, Sangwoo Kim

Localized sources of morphogens, called signalling centres, play a fundamental role in coordinating tissue growth and cell fate specification during organogenesis. However, how these signalling centres are established in tissues during embryonic developmen ...

Nature Portfolio2024

Characterization of the gut-bone marrow axis through bile acid signaling

Alejandro Alonso Calleja

Communication between the intestine and other organs such as the lungs, brain or bones is mediated by several metabolites, like short-chain fatty acids or bile acids, that relay information about nutritional and microbiota status. Bile acids are endogenous ...

EPFL2024

Antibodies expand the scope of angiotensin receptor pharmacology

Patrick Daniel Barth, Shuhao Zhang

G-protein-coupled receptors (GPCRs) are key regulators of human physiology and are the targets of many small-molecule research compounds and therapeutic drugs. While most of these ligands bind to their target GPCR with high affinity, selectivity is often l ...

2024

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

Exploring the interplay of molecular pattern and valency for selective interactions at the bio-interface

Kaltrina Paloja

Cell-cell communication is fundamental for immune balance. Multivalent interactions of surface receptors at immune interfaces drive specific communication, with stimulatory and inhibitory signals guiding the immune outcome. Notably, the valency, affinity, ...

EPFL2023

Regulation and function of a hemicleaved Activin-A processing intermediate in melanoma

Manon Bulliard

Activin-A is a Transforming Growth Factor-B (TGFB)-related cytokine that regulates various biological processes including cell proliferation and differentiation through autocrine, paracrine or endocrine signaling. Activin-A expression is upregulated in mul ...

EPFL2023

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

Development of a novel Chimeric Antigen Receptor (CAR) for its use in Natural Killer (NK) cells for cancer treatment and beyond

Angela Madurga Alonso

The use of CAR technologies has revolutionized cancer treatment. Their unprecedented efficacy against B cell malignancies has opened the doors for a lot of excitement and research in the field. These synthetic receptors are composed of an antigen recogniti ...

EPFL2023

Direct In Vivo Activation of T Cells with Nanosized Immunofilaments Inhibits Tumor Growth and Metastasis

Bart Deplancke, Jorieke Weiden, Guido Van Mierlo

Adoptive T cell therapyhas successfully been implementedfor thetreatment of cancer. Nevertheless, ex vivo expansion of T cells byartificial antigen-presenting cells (aAPCs) remains cumbersome andcan compromise T cell functionality, thereby limiting their t ...

AMER CHEMICAL SOC2023

Site-selective template-directed synthesis of antibody Fc conjugates with concomitant ligand release

Jean-Manuel Segura, David Viertl, Natalia Gasilova

Template-directed methods are emerging as some of the most effective means to conjugate payloads at selective sites of monoclonal antibodies (mAbs). We have previously reported a method based on an engineered Fc-III reactive peptide to conjugate a radionuc ...

Royal Soc Chemistry2023

A single-cell-based characterization of mammalian adipose stem and progenitor cell heterogeneity and function

Pernille Yde Rainer

White adipose tissue (WAT) is a cellularly heterogeneous endocrine organ that not only serves as a reservoir for storing and releasing energy but also actively participates in metabolic homeostasis. Given the current rise in obesity and its associated como ...

EPFL2023

Countering T cell exhaustion and senescence for enhanced adoptive T cell therapies against solid tumors

Yang Zhao

CAR-T cell therapy has shown remarkable success in treating hematopoietic malignancies, but its efficacy in solid tumors is limited by T cell dysfunction, including exhaustion and senescence. In this study, we designed metabolically armored CAR-T cells to ...

EPFL2023

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

Estrogen receptor signaling in the human breast epithelium

Céline Berthe Constantin

Breast cancer is the most diagnosed malignancy in women worldwide, making effective prevention strategies crucial. Hormonal contraceptives, consisting of a synthetic progesterone receptor agonist alone or in combination with an estrogen, are used by millio ...

EPFL2022

Protein Engineering for Personalized therapy and diagnosis

Lixia Wei

Protein Engineering, especially protein post-translational modification (PTM), ex-tends proteomes in a more complex way than one can expect from analysis of their encod-ing genomes. It can activate or deactivate certain catalytic functions, add new desired ...

EPFL2022

Rational design of protein switches: applications in synthetic biology and cancer immunotherapy

Sailan Shui

Synthetic biology aims to engineer cells as miniature biological devices to sense, process, and respond to exogenous stimuli. Protein switches are designed to sense and respond to various molecular queues in a fast and specific manner, which fits the requi ...

EPFL2022

Systematic analysis of biomolecular binding reactions using microfluidic systems

Amir Shahein

Transcription factor binding to a single binding site on DNA and its functional consequence in a promoter context are beginning to be relatively well understood. However, binding to clusters of sites has yet to be characterized in depth, and the functional ...

EPFL2022

Spatially Controlled Activation of Toll-like Receptor 9 with DNA-Based Nanomaterials

Maartje Martina Cornelia Bastings, Alice Comberlato, Marianna Mainardi Koga

First evidence of geometrical patterns and defined distances of biomolecules as fundamental parameters to regulate receptor binding and cell signaling have emerged recently. Here, we demonstrate the importance of controlled nanospacing of immunostimulatory ...

AMER CHEMICAL SOC2022