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Articles by Simone Bruno
MAPK signaling links BRD2 chromatin occupancy to PI3K/AKT inhibitor sensitivity
Abstract Bromodomain and extra-terminal (BET) proteins, BRD2, BRD3, BRD4, and BRDT, couple histone acetylation to transcription by recruiting elongation and transcription factor complexes to chromatin. Although BET proteins are promising therapeutic targets, the functions of individual family members remain incompletely understood. We identify BRD2 as a co-targetable vulnerability with PI3K/AKT inhibition in breast cancer.
Targeted degradation of MDM2 overcomes feedback regulation of p53 signaling in Merkel cell carcinoma models
Abstract MDM2 is transcriptionally activated by the ST-MYCL-Tip60 complex in virus-positive Merkel cell carcinoma (MCC). MDM2 suppresses p53 and is a rational therapeutic target. MDM2 inhibitors face an intrinsic limitation: p53 activation induces MDM2 transcription, creating a feedback loop that blunts inhibitor efficacy. We demonstrate that MDM2 degraders KTX-049 and KT-253 overcome this limitation by collapsing the p53/MDM2 negative feedback loop.
MDM2 degraders for Merkel cell carcinoma: round peg in a round hole
Editor's note Open Access | 10.1172/JCI208535 Published in Volume 136, Issue 13 on July 1, 2026 J Clin Invest. 2026;136(13):e208535. https://doi.org/10.1172/JCI208535. © 2026 Abdulkadir et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. View PDF Varsha Ananthapadmanabhan, Simone Bruno, Leonard Vonk, Yu-Chen Cheng, Abeba Teshager, Benjamin K. Eschle, Charles L. Howarth, Joana S.
Enhancement of sleep slow wave activity using transcranial electrical stimulation with temporal interference: an interim analysis of the STRENGTHEN study
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Abstract Slow waves are oscillations that reflect rhythmic alternation of neuronal activity and mediate key restorative functions of non-rapid eye movement (NREM) sleep. Left ventromedial prefrontal cortex regions are a “hot spot” for slow wave generation. The enhancement of slow wave activity (SWA, 0.5-4 Hz) has been shown to be beneficial, as in improving memory performance.
By Erin Schaeffer, Zhiwei Fan, Simone Bruno, Giulietta Vigueras, Richard Smith, Florian MISSEY, Adam Williamson, Peter Achermann, Stefan Beerli, Myles H. Capstick, Esra Neufeld, Niels Kuster, Robin Goldman, Richard Davidson, William Marshall, Larissa Albantakis, Stephanie Jones, Chiara Cirelli, Melanie Boly, Giulio Tononi, Ido Haber, Beril Mat, Tariq Alauddin, Lindsey Neumann
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Nature
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Stochastic modeling of epigenetic memory
Abstract Here, we review mathematical models of epigenetic memory, focusing on chromatin modifications as key mechanisms to achieve long-term maintenance of epigenetic states. After reviewing the main stochastic modeling frameworks, we focus on stochastic models of chromatin modifications to analyze residence time in memory states, which underpins the long-term maintenance of epigenetic information.
Navigating Melatonin Safety: Fact, Fiction, and Confounders
Data Availability Statement The authors have nothing to report. References 1, , , et al., “Abstract 4371606: Effect of Long-Term Melatonin Supplementation on Incidence of Heart Failure in Patients With Insomnia,” Supplement, Circulation 152, no. Suppl_3 (2025): A4371606, https://doi.org/10.1161/CIRC.152.SUPPL_3.4371606. 2 and , “Suicidal Ideation Following a Single Dose of Melatonin in a Patient With Major Depressive Disorder: A Case Report,” Clinical Case Reports 14, no.
Analog epigenetic memory revealed by targeted chromatin editing
Results We first set out to develop an experimental system to study epigenetic memory in a natural chromosome and the role that histone and DNA methylation play in its establishment. To this end, we constructed a single-copy reporter integrated site-specifically in an endogenous mammalian locus and engineered a set of proteins for targeted epigenetic editing (Figures 2A–2D, S1, S2A, and S2B; STAR Methods; and Tables S1 and S2).
BESTDR: Bayesian quantification of mechanism-specific drug response in cell culture
Abstract Understanding drug responses at the cellular level is essential for elucidating mechanisms of action and advancing preclinical drug development. Traditional dose-response models rely on simplified metrics, limiting their ability to quantify parameters like cell division, death, and transition rates between cell states.
Analog epigenetic memory revealed by targeted chromatin editing
Abstract Chemical modifications to histones and DNA play a crucial role in the regulation of transcription and in the maintenance of chromatin states that are not permissive to gene expression. However, the landscape of gene expression states that these modifications stably maintain remains uncharted. Here, we show that gene expression can be memorized at a wide range of levels thus implementing analog epigenetic memory.
Analog epigenetic cell memory by graded DNA methylation
Abstract Long-term maintenance of gene expression states is required to conserve phenotypic differences among cell types and is often compromised in disease and aging. The state of a gene where transcription is completely inhibited is preserved by chromatin modifications such as DNA methylation and histone H3 lysine 9 trimethylation (H3K9me3). However, how any other gene expression state may be stably maintained remains uncharted.
Analog epigenetic cell memory by graded DNA methylation
Abstract DNA methylation and histone modifications mediate the long-term maintenance of gene expression states and are believed to be established in an all-or-none manner, allowing cells to maintain memory of silenced and active gene states. Here, we investigate whether these modifications can also enable memory of any gene expression level, and thus can equip cells with "analog memory".
Epigenetic OCT4 regulatory network: stochastic analysis of cellular reprogramming - npj Systems Biology and Applications
Abstract Experimental studies have shown that chromatin modifiers have a critical effect on cellular reprogramming, i.e., the conversion of differentiated cells to pluripotent stem cells. Here, we develop a model of the OCT4 gene regulatory network that includes genes expressing chromatin modifiers TET1 and JMJD2, and the chromatin modification circuit on which these modifiers act.
The epigenetic Oct4 gene regulatory network: stochastic analysis of different cellular reprogramming approaches
New Results doi: https://doi.org/10.1101/2023.03.01.530689 Abstract In the last decade, several experimental studies have shown how chromatin modifications (histone modifications and DNA methylation) and their effect on DNA compaction have a critical effect on cellular reprogramming, i.e., the conversion of differentiated cells to a pluripotent state.
Handling shifts during an overnight sailing regatta: comparison between sleep management strategies
ORIGINAL ARTICLE This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.1111/sms.14273 Abstract The study aimed at investigating the association between different sleep management strategies and the final ranking during a one-night sailing race.
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