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CellCharter reveals spatial cell niches associated with tissue remodeling and cell plasticity

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Deconvolution of ex-vivo drug screening data and bulk tissue expression predicts the abundance and viability of cancer cell subpopulations

Alexandre Coudray

Ex-vivo drug sensitivity screening (DSS) allows the prediction of cancer treatment effectiveness in a personalized fashion. However, it only provides a readout on mixtures of cells, potentially occulting important information on clinically relevant cell su ...

EPFL2023

Antibody-peptide conjugates for targeted inhibition of cysteine proteases

Elisa Oricchio

We developed a rational approach to design peptide-based covalent inhibitors and coupled the inhibitors with antibodies for cell-specific delivery. We used this platform to generate antibody-peptide inhibitor conjugates (APICs) that target a family of prot ...

Nature Portfolio2024

CDC7 inhibition impairs neuroendocrine transformation in lung and prostate tumors through MYC degradation

Wouter Richard Karthaus

Neuroendocrine (NE) transformation is a mechanism of resistance to targeted therapy in lung and prostate adenocarcinomas leading to poor prognosis. Up to date, even if patients at high risk of transformation can be identified by the occurrence of Tumor Pro ...

Springer Science and Business Media LLC2024

The CRL5-SPSB3 ubiquitin ligase targets nuclear cGAS for degradation

Pauline Ambre Melenec, Andrea Ablasser, Jonathan Jean-Pierre Ricci, Baptiste Claude André Guey, Chong Liu, Pengbiao Xu, Ying Liu, Lingyun Li

Cyclic GMP-AMP synthase (cGAS) senses aberrant DNA during infection, cancer and inflammatory disease, and initiates potent innate immune responses through the synthesis of 2 ' 3 '-cyclic GMP-AMP (cGAMP)1-7. The indiscriminate activity of cGAS towards DNA d ...

Nature Portfolio2024

The role of LRRK2 in lung adenocarcinoma

Aspasia Gkasti

Lung cancer is the leading cause of cancer-related deaths worldwide and the most common lung cancer subtype is lung adenocarcinoma (LUAD). Frequently mutated genes involve activating mutations in KRAS and loss of function mutations in TP53. LUADs primarily ...

EPFL2024

Alpha1-antitrypsin improves survival in murine abdominal sepsis model by decreasing inflammation and sequestration of free heme

Florian Maria Wurm

Background Excessive inflammation, hemolysis, and accumulation of labile heme play an essential role in the pathophysiology of multi-organ dysfunction syndrome (MODS) in sepsis. Alpha1-antitrypsin (AAT), an acute phase protein with heme binding capacity, i ...

Frontiers Media Sa2024

Distinct ultrastructural phenotypes of glial and neuronal alpha-synuclein inclusions in multiple system atrophy

Henning Paul-Julius Stahlberg, Marta Di Fabrizio, Amanda Jennifer Lewis, Domenic Burger

Multiple System Atrophy is characterized pathologically by the accumulation of alpha-synuclein (aSyn) into glial cytoplasmic inclusions (GCIs). The mechanism underlying the formation of GCIs is not well understood. In this study, correlative light and elec ...

2024

Exploring the role of cGAS-STING-mediated inflammation in age-associated neurodegeneration and antitumor immunity

Natasha Ella Samson

Inflammation stands as a dynamic and intricate biological process, promoting vital defence mechanisms against harmful stimuli, including infections and injuries, to drive pathogen clearance and healing. On one hand, these responses can manifest acutely and ...

EPFL2024

Tumor-educated Gr1+CD11b+cells drive breast cancer metastasis via OSM/IL-6/JAK-induced cancer cell plasticity

Nadine Fournier, Annamaria Kauzlaric, Manon Bulliard, Rachel Marcone

Cancer cell plasticity contributes to therapy resistance and metastasis, which represent the main causes of cancer-related death, including in breast cancer. The tumor microenvironment drives cancer cell plasticity and metastasis, and unraveling the underl ...

Amer Soc Clinical Investigation Inc2024

Clinically compliant cryopreservation of differentiated retinal pigment epithelial cells

Cheng Zhao, Gioele La Manno, Alex Russell Lederer

Background aims: Age-related macular degeneration (AMD) is the most common cause of blindness in elderly patients within developed countries, affecting more than 190 million worldwide. In AMD, the retinal pigment epithelial (RPE) cell layer progressively d ...

Elsevier Sci Ltd2024

NMR and MS reveal characteristic metabolome atlas and optimize esophageal squamous cell carcinoma early detection

Lijing Xin

Metabolic changes precede malignant histology. However, it remains unclear whether detectable characteristic metabolome exists in esophageal squamous cell carcinoma (ESCC) tissues and biofluids for early diagnosis. Here, we conduct NMR- and MS-based metabo ...

Nature Portfolio2024

In vivo polydopamine coating of Rhodobacter sphaeroides for enhanced electron transfer

Ardemis Anoush Boghossian, Melania Reggente

Recent advances in coupling light-harvesting microorganisms with electronic components have led to a new generation of biohybrid devices based on microbial photocatalysts. These devices are limited by the poorly conductive interface between phototrophs and ...

2024

Single-cell epigenomic reconstruction of developmental trajectories from pluripotency in human neural organoid systems

Fides Zenk

Cell fate progression of pluripotent progenitors is strictly regulated, resulting in high human cell diversity. Epigenetic modifications also orchestrate cell fate restriction. Unveiling the epigenetic mechanisms underlying human cell diversity has been di ...

Nature Portfolio2024

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

Andrea Agnoletto

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

6-diazo-5-oxo-l-norleucine prodrugs

Xile Hu, Li Tang, Céline Jasmin Prange, Nadia Yasmina Ben Sayed

The present invention relates to 6-diazo-5-oxo-L-norleucine prodrugs having reduced toxicity and increased tumor specificity and to their therapeutic use for treating cancer. ...

2024

Multimodal transcriptomic atlases of mouse spinal cord injury

Matthieu Pierre Gautier

A spinal cord injury (SCI) triggers a cascade of molecular and cellular responses involving inflammatory cell infiltration and cytokine release, apoptosis, demyelination, excitotoxicity, ischemia, and the formation of a fibrotic scar surrounded by an astro ...

EPFL2024

The conceptual foundations of innate immunity: Taking stock 30 years later

Bruno Lemaitre

While largely neglected over decades during which adaptive immunity captured most of the attention, innate immune mechanisms have now become central to our understanding of immunology. Innate immunity provides the first barrier to infection in vertebrates, ...

2024