The Dobreva Lab

We study the interplay between genetics and epigenetics in shaping cell identity, plasticity, and resilience during development and in disease.

[Nilimesh Das (নীলিমেশ দাস) @nilimeshda]

How RNA methylation reshape condensates?

It binds FUS more strongly and is associated with larger, more stable condensates.

A small chemical modification with potentially important consequences for the organization of RNA–protein assemblies.
https://t.co/CEWOGevEBO

[Gene Regulation @generegulation]

Guo et al, 2026. P-TEFb regulates nucleosome positioning at promoters https://t.co/IhsO8EvrMr
➡️Inhibition of P-TEFb, the kinase component of the super elongation complex (SEC), disrupts nucleosome positioning and leads to cryptic transcription within the early elongation zone

[Science Magazine @ScienceMagazine]

Healthy remodeling of adipose tissue helps maintain metabolic balance and protect surrounding organs. But when this process is disrupted, it can lead to harmful cellular changes that contribute to metabolic disease and that damage nearby tissues. Although weight loss can reverse many aspects of fat-tissue dysfunction, some changes may persist.

According to a new #ScienceReview, understanding which changes are reversible and which leave lasting effects is key to helping researchers develop treatments that don’t just reduce fat mass, but also restore healthy fat-tissue function and improve metabolic resilience.

Learn more: https://t.co/kUECLBFH1C

[Siyuan (Steven) Wang @SStevenWang]

Glad to share our latest publication in @naturemethods: Nondisruptive 3D profiling of combinations of epigenetic marks in single cells.

Epigenetic states and 3D chromatin folding are critical regulators of many genomic functions. While these mechanisms are known to be closely interlinked, studying their relationship remains challenging due to technical limitations. Sequencing-based single-cell or spatial histone modification profiling techniques often suffer from low sequencing read count per cell or per spatial spot, limiting gene-locus-specific analyses at the single-cell level. A recent imaging-based method termed epigenomic MERFISH (Cell 2022) enabled single-cell in situ histone modification profiling in a locus-specific manner with high genomic resolution (~2 kb). However, epigenomic MERFISH is limited to profiling only one epigenetic mark at a time, performs poorly when profiling repressive mark, and as we show in this work, disrupts the 3D genome thus prohibiting 3D genome co-profiling.

To address these limitations, we developed Epigenetic Proximity Hybridization Reaction (Epi-PHR), an imaging-based technology that represents the first epigenetic profiling method that:
🧬1) can simultaneously profile more than one histone modification and chromatin associated protein at numerous genomic loci with high genomic resolution,
🧬2) is non-disruptive and retains 3D chromatin architecture, and
🧬3) inherently provides single-cell, single-copy and in situ information.

We first demonstrated Epi-PHR's sensitivity at small genomic targets of 2 kb. We further showcased multiplexed Epi-PHR to profile combinations of epigenetic marks (including both active and repressive marks) at 200 genes in the same single cells in culture and tissue. Finally, we developed allelic Epi-PHR and combined it with fine-scale chromatin tracing to simultaneously profile epigenetic state and chromatin folding at the same genomic target with parent-of-origin specificity, generating the first single-cell phased examination of histone mark deposition and 3D genome architecture at an imprinted locus by any technique.

In the study of the imprinted locus, surprisingly we found among the maternal copies of this locus, the relationship between the histone mark and a chromatin domain boundary is opposite to what one would expect. This insight cannot be derived from existing bulk allele-specific CUT&RUN and Hi-C approaches. Our unexpected finding was uniquely enabled by allelic Epi-PHR combined with chromatin tracing.

We expect Epi-PHR will find broad application in diverse biomedical contexts. This work was co-led by Dr. Yanbo Chen, Dr. Jonathan Radda, and Dr. Myles Alderman III, and was done in collaboration with my @YaleGenetics colleague Professor Andrew Xiao. Thank you all my co-authors for your contributions to this work!

Link to paper: https://t.co/iXoPN8D8lr

[Endothelial Cell News @endothelialnews]

Hot off the press in @Nature! 🤩

Scientists including Irene Garcia-Gonzalez and Susana Rocha used iFlpMosaics and iSuRe–HadCre to induce and track genetic mosaics of #EndothelialCells lacking VEGFR2 during the entire embryonic and postnatal development.

Their work demonstrates venousization as a mechanism of adaptation and resistance to VEGF signaling loss during #angiogenesis.

https://t.co/jo5raw14Bm

#OpenAccess 🔓

[Eric Topol @EricTopol]

Caloric restriction (CR), in many species, extends lifespan. In a new study, CR reduced the accumulation of somatic mutations, but that was not enough to account for change in lifespan. Work in the experimental model.
https://t.co/H7MQfq75Gk
https://t.co/YA2FzC7FQZ

[Sagar Bapat @bapat_lab]

Our @Nature paper is out!

It's been known for a while that long-term dietary habits can affect how our immune system behaves. But what about much briefer changes in diet?

In mice, we found that even a few days of dietary change (think cheat days...or perhaps salad Sundays) at the onset of inflammation can profoundly alter disease severity and establish lasting inflammatory memory in tissues, even after the diet changes back.

https://t.co/AO5fjQjmwR

This work was led by two extraordinarily dedicated and inexhaustible members of our lab: former graduate student @OwenJ457 and former technician John Tayeri. It was also an exercise in collaborative science as many labs @UCSF and @Stanford came together to bring this over the finish line - special thanks to @gardnerlabUCSF, @Molofsky_lab, @alexis_combes, @Treg_Mike. Deeply grateful to everyone who contributed!

[Cell Metabolism @Cell_Metabolism]

New! Online now: Postnatal depression-associated breastmilk extracellular vesicles mediate intergenerational effects on offspring neurodevelopment dlvr.​it/TW4y5s

[Luciano Di Croce @ludicroce]

Pleased to share our new study on the role of Polycomb in leukemia!
We show that loss of PHF19 promotes stem-like features and reduced treatment response in AML, and identify PHFScore, a new signature to predict patient prognosis.
https://t.co/I6G0EnpVEs

[Eric Topol @EricTopol]

Spotlighting the macrophage cells in our blood and tissue, their role in diseases, and targeted interventions
https://t.co/dmcdQJCrnj @ImmunityCP

[nature @Nature]

A massive study of more than 100,000 people finds surprise connection between ‘good’ body fat and improved mental health

https://t.co/i5Wbqf48Qq

[Luis J. Castro-Vega @LuisJaimeCastr3]

https://t.co/Nq6kdbudcP

[Nature Metabolism @NatMetabolism]

Maternal obesity imprints methylation marks in oocytes to drive intergenerational metabolic dysfunction dlvr.​it/TVl8W9

[Epigenome Technologies Inc. @EpigenomeTech]

Epigenetics Update - HP1α binding creates a local barrier against transcription activation and persists during chromatin decondensation https://t.co/LhrQnHxugh

Robin Weinmann and @KarstenRippe @DKFZ) in @MolecularCell

#Epigenetics #Chromatin #HP1
---

https://t.co/WmSYDGWPJD

[Shilatifard Lab @ShilatifardLab]

Space, the final frontier! 🚀 Check out this amazing feat of discovery from my colleague @yuefeng_1 and team.  They report the first “Spatial-ATAC-Hi-C”, a method that maps 3D genome organization and chromatin accessibility together while preserving the spatial context of tissues. They have applied this method to brain and tumor samples and revealed cell-specific transcriptional regulation, oncogenic alterations, and clonal heterogeneity within their native tissue microenvironment. A fascinating new window into the spatial organization of the genome! Congratulations Feng and colleagues! @NU_BMG_SQE @NUFeinbergMed @naturemethods @Nature @CellPressNews @ScienceMagazine @theNASciences @theNAMedicine https://t.co/QaSRojjFhe

[Dr. Thomas Ichim @exosome]

Breakthrough Nature paper...

Brain neurons record autoimmune activity and remember it....

https://t.co/GBpRqpX2jC

[nature @Nature]

A massive genomic study has linked mutations in a specific gene to an increased proportion of muscle, decreased levels of belly fat and blood sugar and a reduced risk of conditions including heart disease

https://t.co/vulEGsX5Ws

[Junedh M. Amrute @junedh_amrute]

https://t.co/4UxAw538rm

[Molecular Cell @MolecularCell]

Online Now: METTL3 promotes cell-cycle progression via activation of transcriptional elongation https://t.co/qYhdXWjuo6

[Science Magazine @ScienceMagazine]

A new study in Science provides a comprehensive atlas of DNA methylation and 3D genome architecture across human cell types.

Learn more: https://t.co/A4gl6Se9DJ