iiinova — where your digital self keeps evolving

valeramponi.bsky.social @valeramponi.bsky.social · 08/01/2025

🧵10/ And last but not least, thanks to @AACR for choosing our cover for the first issue of 2025 of Cancer Research and to Clemens A. Schmitt for the commentary on Cancer Research: Persistence and/or Senescence: Not So Lasting at Last? aacrjournals.org/cancerres/ar...

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valeramponi.bsky.social @valeramponi.bsky.social · 08/01/2025

🧵9/ Incredibly grateful for the fantastic mentorship, environment & colleagues in Manuel Serrano's lab. A huge thank to @ficzlab.bsky.social's lab, @martakova.bsky.social, Camille Stephan-Otto Attolini, Laia Richart, and Oscar Yanes. A special thank to @irbbarcelona.org and its amazing facilities✨

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valeramponi.bsky.social @valeramponi.bsky.social · 08/01/2025

🧵8/ Silencing of the methyltransferases responsible for H4K20 trimethylation, led to a derepression of inflammatory genes in persister cells and resulted in loss of survival, unravelling another vulnerability of this cell population.

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valeramponi.bsky.social @valeramponi.bsky.social · 08/01/2025

🧵7/ The loss of H4K20me3 in the promoters of inflammatory genes may underlie, at least in part, the upregulation of these pathways in senescent cells. Conversely, the gain of H4K20me3 provides an epigenetic explanation for the lack of SASP and IFN gene expression in DTP.

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valeramponi.bsky.social @valeramponi.bsky.social · 08/01/2025

🧵6/ CUT&Tag of H4K20me3 revealed a group of promoter regions related to inflammatory pathways with discrepant behaviour between TIS and DTP: senescent cells present reduced H4K20me3 at these promoters, while persister cells present an increase in the levels of this mark.

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valeramponi.bsky.social @valeramponi.bsky.social · 08/01/2025

🧵5/ Based on the importance of 1C metabolism for histone methylation reactions, we looked at the levels of histone methylation marks. We detected an increase in H4K20me3 in persister and senescent cancer cells compared to proliferating cancer cells.

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valeramponi.bsky.social @valeramponi.bsky.social · 08/01/2025

🧵4/ Through a CRISPR/Cas9 screen, we identify inhibition of 1C metabolism as an actionable vulnerability of DTPs. The 1C metabolism is important for providing methyl groups used for methylation of both histones and DNA.

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valeramponi.bsky.social @valeramponi.bsky.social · 08/01/2025

🧵3/ Senescent and persister cancer cells are both sensitive to the BCL2 family inhibitor navitoclax, whose efficacy is attributable to the specific inhibition of BCL-XL in both types of cell-cycle arrest.

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valeramponi.bsky.social @valeramponi.bsky.social · 08/01/2025

🧵2/ Interestingly, persister cells lack the SASP and the transcriptional programs associated with IFN signalling, including the absence of MHC-I upregulation.

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valeramponi.bsky.social @valeramponi.bsky.social · 08/01/2025

🧵1/ We characterize a model of drug-tolerant persister cancer cells driven by INK128, an ATP-competitive inhibitor of mTOR. We provide a characterisation of distinct and shared features between therapy-induced senescent (TIS) and drug-tolerant persister (DTP) cancer cells.

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valeramponi.bsky.social @valeramponi.bsky.social · 27/03/2024

The last 4 and half years have been a rollercoaster of emotions. I have learnt so much from everyone I have crossed my path with. Big thanks to all ❤️ The PhD is a long road, but I can say now that is totally worth it when you are surrounded by a great environment and science.

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valeramponi.bsky.social @valeramponi.bsky.social · 27/03/2024

Almost two weeks ago I defended my PhD and I still can not believe it. I would like to thank the members of the tribunal (@KP_twitt_llo, @Joffreypelleti1, @narita_lab) for the amazing discussion and the great suggestions. Thanks to everyone that has been part of this journey.

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valeramponi.bsky.social @valeramponi.bsky.social · 23/06/2023

Such a cool paper!! - SAM mediates Suv39h1 direct methylation of cGAS to suppress its activity. - Methionine deprivation leads to cGAS activation, contributing to antitumor immunity. www.cell.com/cancer-cell/fulltext/S…

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valeramponi.bsky.social @valeramponi.bsky.social · 23/03/2023

Very cool mathematical model on how senescence spreading is "contained" after tissue injury. Someone will have to prove it by experimental evidences! Modelling the Dynamics of Senescence Spread www.biorxiv.org/content/10.1101/202…

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valeramponi.bsky.social @valeramponi.bsky.social · 20/12/2022

It has been great closing the year with 2 days of celebration for the 25 years of Manuel Serrano’s lab! It was really inspiring to hear many different stories and experiences from the different generations of scientists that were in a way shaped by Manolo. Thanks to all of you!

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valeramponi.bsky.social @valeramponi.bsky.social · 16/11/2022

Today Manuel Serrano gave us some insights about the intermediates states of in vivo #reprogramming and their importance during the process of #rejuvenation. If you wanna know more about this, check three of the last papers from the lab (Chondronasiou et al, Meléndez et al)

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valeramponi.bsky.social @valeramponi.bsky.social · 16/11/2022

Last day of the “Quantitative dynamics of aging and premalignancy”. Many thanks to the organizers @AlejoFraticelli and @SalvadorAznar3 for putting together such a great conference with so many outstanding speakers. I have learnt a lot. Looking forward for the next one!

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valeramponi.bsky.social @valeramponi.bsky.social · 05/11/2022

Have a look at this new story from Manuel Serrano’s lab about #chemotherapy, #senescent cells and a very new player.. #PD-L2 ! Great job @josealbertold, @lalingu, @Ines_Marin_G and all the others :) www.biorxiv.org/content/10.1101/202…

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valeramponi.bsky.social @valeramponi.bsky.social · 29/10/2022

Amazing work from @Ines_Marin_G, led by Manuel Serrano And @FedericoPietr12 that highlights the #immunogenic potential of #senescent cells and its role against tumor development. Great job guys!! aacrjournals.org/cancerdiscovery/ar…...

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valeramponi.bsky.social @valeramponi.bsky.social · 11/09/2022

Check out our new paper on the regulation of the senescent secretome: onlinelibrary.wiley.com/doi/10.1111…

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