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Chiara Masnovo

@chiaramasnovophd.bsky.social

Genomic instability | Postdoc in the @ChowdhuryLab at DFCI/Harvard Medical School | Ph.D. from the Mirkin Lab at Tufts. 🇮🇹

80 Posts455 Follower1020 Folgt
Chiara Masnovo@chiaramasnovophd.bsky.social · 2mo ago

Do you or anyone you know want to get involved in research but don’t know where to start? I put together this short article breaking down different strategies to find a lab! Please share with your undergraduate student network! 🔬 How did you find your first research position?

How to find a research lab as an undergraduate student | Chiara Masnovo

Want to get involved in research but don't know where to start? I put together a short article breaking down these different pathways and how to approach each one. 📚 Structured programs (UROP, REUs,...

linkedin.com

Chiara Masnovo@chiaramasnovophd.bsky.social · 5mo ago

🚨 New News 🚨 I am excited to share that I have been awarded the American Cancer Society Postdoctoral Fellowship. For the next three years, this will allow me to investigate the mitotic role of 53BP1 and how it contributes to genome stability! Thank you to all my mentors and colleagues.

Chowdhury Lab@chowdhurylab.bsky.social · 5mo ago

Congratulations to @chiaramasnovophd.bsky.social on receiving the @americancancersoc.bsky.social Postdoctoral Fellowship! 🎉 Her project will be defining the DNA Repair Independent Mitotic Role of 53BP1 Well deserved recognition of outstanding work!

@derianolab.bsky.social · 9mo ago

🚨 Check out our latest article! 🚨 Spoiler: when NHEJ is out, polymerase theta steps in to fix persistent G1-phase breaks during the next S phase — not in mitosis! And for our fellow B cell fans, we explore how Pol θ contributes to immunoglobulin class switching. @natcomms.nature.com rdcu.be/eRTSe

Polymerase theta repairs persistent G1-induced DNA breaks in S-phase during class switch recombination

Nature Communications - NHEJ is the primary repair pathway during class switch recombination. Here the authors show that in absence of NHEJ, Pol θ repairs persistent G1-induced breaks in...

rdcu.be

@derianolab.bsky.social · 7mo ago

✅ Hundreds of genes show shared, distinct, or opposing effects in BRCA1 vs BRCA2 deficient cells, with direct implications for prevention and therapy based on BRCA mutation status.

@derianolab.bsky.social · 7mo ago

🚨 New preprints from the lab! www.biorxiv.org/content/10.6... How do cells adapt when BRCA1 or BRCA2 are suddenly lost? 🧬 We built a genome scale genetic adaptation map to find out. #BRCA #CRISPR #DNARepair #Cancer

The FANCM-RMI1/2 complex promotes genomic instability and PARP inhibitor sensitivity in BRCA2-deficicient cells.

Cancer cells lacking BRCA1 or BRCA2 must adapt to survive and proliferate despite defective DNA repair and high genomic instability. Restoration of homologous recombination (HR) through loss of DNA end protection rescues growth defects and promotes PARP inhibitor (PARPi) resistance in BRCA1-deficient cells; however, the genetic basis of adaptation to BRCA2 loss remains largely unexplored. To delineate BRCA1- and BRCA2-specific adaptation trajectories, we established a fully isogenic screening platform in mouse embryonic stem cells engineered for acute depletion of either protein. This approach uncovered hundreds of genes with shared, distinct, or even opposing effects between the two BRCA-deficiency states. We identified FANCM and its interacting partners RMI1/2, CENPS/MHF1, CENPX/MHF2, and FAAP24 as essential in BRCA1-deficient cells but toxic in BRCA2- deficient contexts. Loss of FANCM in BRCA2-deficient cells alleviated genomic instability and proliferation defects by preventing RMI1/2-dependent replication fork degradation, without rescuing HR. Moreover, we show that the FANCM-RMI1/2 complex drives PARPi sensitivity in both mouse and human BRCA2-deficient cells, in contrast to the 53BP1-SHLD-CST axis in BRCA1-deficient cells. These findings reveal distinct adaptation routes to BRCA1 and BRCA2 loss and establish FANCM as a determinant of BRCA2-specific vulnerability and therapeutic response, with direct implications for tailoring prevention and therapy according to BRCA mutation status. ### Competing Interest Statement C.J.L. makes the following disclosures: receives and/or has received research funding from: AstraZeneca, Merck KGaA, Artios, Neophore, FoRx. Received consultancy, SAB membership or honoraria payments from: FoRx, Syncona, Sun Pharma, Gerson Lehrman Group, Merck KGaA, Vertex, AstraZeneca, Tango Therapeutics, 3rd Rock, Ono Pharma, Artios, Abingworth, Tesselate, Dark Blue Therapeutics, Pontifax, Astex, Neophore, Glaxo Smith Kline, Dawn Bioventures, Blacksmith Medicines, ForEx, Ariceum. Has stock in: Tango, Ovibio, Hysplex, Tesselate, Ariceum. C.J.L. is also a named inventor on patents describing the use of DNA repair inhibitors and stands to gain from their development and use as part of the ICR Rewards to Inventors scheme and also reports benefits from this scheme associated with patents for PARP inhibitors paid into CJL's personal account and research accounts at the Institute of Cancer Research. 020

biorxiv.org

The Coster lab 🧬🔬@costerlab.bsky.social · 8mo ago

Read our latest work - a comprehensive review on how DNA secondary structures affect replication. Very proud of Adi, Maria and Billie for their monumental effort. They've covered a large body of literature while proposing updated models. Open Access in DNA Repair: doi.org/10.1016/j.dn...

How DNA secondary structures drive replication fork instability

DNA secondary structures, such as hairpins, cruciforms, triplexes, G-quadruplexes and iMotifs, are common, dynamic features that replication forks rou…

sciencedirect.com

Chiara Masnovo@chiaramasnovophd.bsky.social · 8mo ago

Starting a new daily series. The Postdoc Diary. Postdoc diary, day 1: today, as I entered the lab, I was listening to a podcast that had me dying laughing, my PI walked in and I just laughed in his face for two minutes straight. I think he appreciated the morning joy! 🤣

Chiara Masnovo@chiaramasnovophd.bsky.social · 12mo ago

Congrats to @susankilgas.bsky.social and all other authors on this fantastic publication! Make sure to check it out.

Chowdhury Lab@chowdhurylab.bsky.social · 12mo ago

Excited to share our new paper from the Buhrlage lab & Chowdhury labs! 🎉 We designed CAS-010, a selective, low nanomolar USP28 inhibitor that reduces p53 transcriptional activity, mimics p53 loss & disrupts 53BP1-USP28 binding, offering new insights into USP28 function. www.cell.com/cell-chemica...

Chiara Masnovo@chiaramasnovophd.bsky.social · last yr.

📣 New paper from the lab 📣 showing how the CST complex inhibits end resection during DNA double-strand break repair! Congrats to all authors.

Chowdhury Lab@chowdhurylab.bsky.social · last yr.

Excited to share our latest publication, out in @science.org! We define a key role for the CST complex in double-strand break repair pathway choice. This study was conducted in close collaboration with the Sung lab at UT Health San Antonio. Congrats to @michelleswift.bsky.social and all authors!