Publications associées à Target of rapamycin modulators of and use thereof

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

Whole-genome doubling drives oncogenic loss of chromatin segregation

Elisa Oricchio, Natalya Katanayeva, Ruxandra-Andreea Lambuta, Juan Diaz Miyar, Giovanni Ciriello, Daniele Tavernari

Whole-genome doubling (WGD) is a recurrent event in human cancers and it promotes chromosomal instability and acquisition of aneuploidies(1-8). However, the three-dimensional organization of chromatin in WGD cells and its contribution to oncogenic phenotyp ...

NATURE PORTFOLIO2023

Targeting the Progesterone Receptor in Breast Cancer: Mind the Short Form!

Cathrin Brisken, Carlos Henrique Venturi Ronchi

The presurgical window of opportunity trial (WOT) MIPRA provides evidence that neoadjuvant treatment with the prog-esterone receptor (PR) antagonist mifepristone (RU486) may benefit patients with estrogen receptor-positive (ER+) breast cancer characterized ...

AMER ASSOC CANCER RESEARCH2023

Development of next-generation microfluidic systems for enhanced, faster, and cost-effective immunoassays for tissue diagnostics - Ac electrothermal flow & Acoustofluidics

Muaz Salama Abdelmonem Draz

The application of microfluidics in the field of surface-based assays and more specifically, the spatial molecular profiling of tumor tissues has gained a lot of interest, especially with the increased interest in personalized medicine and targeted therapy ...

EPFL2023

Deciphering the molecular events leading to the global restoration of the chromatin landscape during mitotic exit

Silja Michelle Placzek

Two fundamental properties of embryonic stem cells (ESCs) are their ability to self-renew and differentiate into all somatic cell types. Maintenance of their identity faces major challenges when transitioning through mitosis, as most DNA-binding proteins a ...

EPFL2023

Role of the androgen receptor in the human breast epithelium

Fabio De Martino

Breast cancer is the most common malignancy in women worldwide and understanding the risk factors affecting it is key for prevention. The relative risk of developing breast cancer is related to exposure to both endogenous hormones and exogenous natural and ...

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

Mitochondrial respiratory chain dysfunction disrupts intracellular cholesterol homeostasis

Christopher Tadhg James Wall

Mitochondrial diseases are rare and severe conditions with debilitating symptoms. Biochemical defects in mitochondria however are common. The difference between these two frequencies is suspected to lie in the capability of the cells to adapt to the homeos ...

EPFL2022

Epigenetic memory aids: Synaptic and molecular effects of HDAC inhibition that support memory formation

Allison Marie Burns

Learning and memory rely on synaptic communication in which intracellular signals are transported to the nucleus to stimulate transcriptional activation. Memory induced transcriptional increases are accompanied by alterations to the epigenetic landscape an ...

EPFL2022

Generating macrocyclic inhibitors of protein-protein interactions

Gontran Sangouard

Protein-protein interactions (PPIs) play important roles in many diseases and their modulation is an attractive strategy for developing new therapeutics. However, the relatively large and often flat binding surfaces of PPIs makes the development of inhibit ...

EPFL2022

Modulation of Subcellular Redox Homeostasis with Trialkylphosphines

Jade Noémie Nam Nguyen

Redox homeostasis is essential for cell function and its disruption is associated with multiple pathologies. Redox balance is largely regulated by the relative concentrations of reduced (GSH) and oxidized (GSSG) glutathione. In eukaryotic cells, this ratio ...

SWISS CHEMICAL SOC2022

Wigner Formulation of Thermal Transport in Solids

Nicola Marzari, Michele Simoncelli

Two different heat-transport mechanisms are discussed in solids. In crystals, heat carriers propagate and scatter particlelike as described by Peierls's formulation of the Boltzmann transport equation for phonon wave packets. In glasses, instead, carriers ...

American Physical Society2022

Reduced NCOR2 expression accelerates androgen deprivation therapy failure in prostate cancer

Gerard Llimos Aubach

This study addresses the roles of nuclear receptor corepressor 2 (NCOR2) in prostate cancer (PC) progression in response to androgen deprivation therapy (ADT). Reduced NCOR2 expression significantly associates with shorter disease-free survival in patients ...

CELL PRESS2021

The box C/D snoRNP assembly factor Bcd1 interacts with the histone chaperone Rtt106 and controls its transcription dependent activity

Benjamin Marcel Daniel Rothé

Biogenesis of eukaryotic box C/D small nucleolar ribonucleoproteins initiates co-transcriptionally and requires the action of the assembly machinery including the Hsp90/R2TP complex, the Rsa1p:Hit1p heterodimer and the Bcd1 protein. We present genetic inte ...

Nature Research2021

Epigenetic remodelling of enhancers in response to estrogen deprivation and re-stimulation

Ludovica Vanzan

Estrogen hormones are implicated in a majority of breast cancers and estrogen receptor alpha (ER), the main nuclear factor mediating estrogen signaling, orchestrates a complex molecular circuitry that is not yet fully elucidated. Here, we investigated geno ...

OXFORD UNIV PRESS2021

Computational identification and experimental characterization of preferred downstream positions in human core promoters

Philipp Bucher, René Dreos

Author summary Transcription of genes by the RNA polymerase II enzyme initiates at a genomic region termed the core promoter. The core promoter is a regulatory region that may contain diverse short DNA sequence motifs/elements that confer specific properti ...

2021

LncRNA Ctcflos orchestrates transcription and alternative splicing in thermogenic adipogenesis

Bart Deplancke, Petra Catalina Schwalie

The recruitment of thermogenic brite adipocytes within white adipose tissue attenuates obesity and metabolic comorbidities, arousing interest in understanding the underlying regulatory mechanisms. The molecular network of brite adipogenesis, however, remai ...

WILEY2021

KAP1 targets actively transcribed genomic loci to exert pleomorphic effects on RNA polymerase II activity

Didier Trono, Annamaria Kauzlaric, Marco Cassano, Suk Min Jang, Evaristo Jose Planet Letschert

KAP1 (KRAB-associated protein 1) is best known as a co-repressor responsible for inducing heterochromatin formation, notably at transposable elements. However, it has also been observed to bind the transcription start site of actively expressed genes. To a ...

2020

Targeting the oncogenic signaling of the transcription factor STAT3 with potent and selective monobody inhibitors

Grégory La Sala

Many targeted cancer therapies fail to improve the overall survival of patients. Limitations involve low drug selectivity and the rapid development of resistance. Moreover, the majority of oncogenic drivers presently remain considered as undruggable as th ...

EPFL2020

Macrophage NCOR1 Deficiency Ameliorates Myocardial Infarction and Neointimal Hyperplasia in Mice

Johan Auwerx, Hongwei Zhu, Yan Liu, Yuan Liu, Shuai Shao

Background NCOR1 (nuclear receptor corepressor 1) is an essential coregulator of gene transcription. It has been shown that NCOR1 in macrophages plays important roles in metabolic regulation. However, the function of macrophage NCOR1 in response to myocard ...

2020