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Lauren Murphy

@l-cmurphy.bsky.social

45 followers 74 following 42 posts

Postdoctoral Scientist at the University of Oxford. Interested in platelet and cancer biology 🩸 http://www.linkedin.com/in/lauren-c-murphy

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Lauren Murphy @l-cmurphy.bsky.social · Aug 14

🚨 New paper alert! 🚨 I’m thrilled and proud to share that our latest work has just been published in @science.org! 🎉 🧽

📖 Read our paper here: doi.org/10.1126/sci...

🎬 Watch a summary: youtu.be/MttCA3GGWEM

🧵 Or keep reading for the key points! 🔑 1/19

Lauren Murphy @l-cmurphy.bsky.social · Aug 18

Thanks for sharing ‪@brian.teague.bio‬!! Glad you enjoyed reading it!! Platelets are the best! 🩸🧽

Lauren Murphy @l-cmurphy.bsky.social · Aug 18

‪Thanks for sharing @jessiemacalpine.bsky.social‬!

Lauren Murphy @l-cmurphy.bsky.social · Aug 18

Thanks for sharing Alba!!! Hope you're good and maybe see you at ISEH??? 🩸🧬

Lauren Murphy @l-cmurphy.bsky.social · Aug 16

Thanks Judit!! 🧽

Reposted by Lauren Murphy

Eric Topol @erictopol.bsky.social · Aug 14

Platelets sequester and harbor cell-free tumor DNA, which could enhance our ability to make early, microscopic diagnosis of cancer
@science.org

science.org/doi/10.1126/...
science.org/doi/10.1126/...

Lauren Murphy @l-cmurphy.bsky.social · Aug 15

Thank you for highlighting our research Adrian Tsui and Dennis Lo! 🧽

The ins and outs of circulating DNA | Science www.science.org/doi/10.1126/...

The ins and outs of circulating DNA

DNA sequestered in circulating platelets could inform early tumor diagnosis

www.science.org

Lauren Murphy @l-cmurphy.bsky.social · Aug 14

⭐️Above all, thanks to the patients who contributed samples and inspired this work!⭐️ 19/19

Lauren Murphy @l-cmurphy.bsky.social · Aug 14

We are incredibly grateful for fantastic support from institutions and funders, critical to enabling this work: @cancerresearchuk.org‬, @ludwigcancer.bsky.social, ‪oxfordcancer.bsky.social, imm.ox.ac.uk‬,
@rdm.ox.ac.uk‬ and @exeter.ox.ac.uk‬ 🌍 18/19

Lauren Murphy @l-cmurphy.bsky.social · Aug 14

Thank you to our reviewers for dedicating their time and energy to thoughtfully improving the manuscript, and to @sarahhross.bsky.social‬
and @science.org for a smooth editorial process.📚 17/19

Lauren Murphy @l-cmurphy.bsky.social · Aug 14

We are also very grateful to those who came on board with the idea especially Eric O’Neil, Ian Hitchcock @ian-hitchcock.bsky.social, Michael Desborough and Manu Vatish ‪oxfordwomenshealth.bsky.social‬
who helped us brainstorm and collect samples. 🧠 16/19

Lauren Murphy @l-cmurphy.bsky.social · Aug 14

This project was a true team effort and would not have been possible without so many incredible colleagues: Jeanne Inchauspé, Giampiero Valenzano, Chris Gregory, Pamella Holland @edinuni-irr.bsky.social
Paul Rees, and Benjamin Schuster-Böckler ‪‪‪dagams.bsky.social 🤝 15/19

Lauren Murphy @l-cmurphy.bsky.social · Aug 14

With huge thanks to my PhD supervisors for their endless enthusiasm and support: Beth Psaila @bethpsaila.bsky.social, Simon Leedham ‪leedham-simon.bsky.social and Adam Mead @adammead.bsky.social‬ ✨14/19

Lauren Murphy @l-cmurphy.bsky.social · Aug 14

So much cool biology to follow up…✉️ Take home message: a substantial % of cfDNA is contained within platelets. This info is being missed by current protocols that extract cfDNA from platelet-depleted plasma! 🗓️13/19

Lauren Murphy @l-cmurphy.bsky.social · Aug 14

Why do plts do this?! Maybe to help clear cfDNA from plasma, preventing non-specific immune activation. We showed that cfDNA is higher in low plt counts. After gobbling up DNA fragments, do plts then deploy it targeting immune activation to where it is needed? 🍽️🤔 12/19

Lauren Murphy @l-cmurphy.bsky.social · Aug 14

In patients, we showed cancer-derived DNA in both advanced and early-stage cancer. Remarkably, we even detected mutant BRAF alleles in people with “pre-cancer”–small colon polyps! Polyps increase CRC risk and are hard to detect; plt DNA may be an early molecular flag! 🚩11/19

Lauren Murphy @l-cmurphy.bsky.social · Aug 14

But does this happen in vivo? With ‪leedham-simon.bsky.social and Eric O'Neil, we showed plts contain cancer mutations in colorectal and pancreatic models. In many cases, there was more tumor DNA in plts than plasma, indicating that including plt DNA would add value to screening! 🐁 10/19

Lauren Murphy @l-cmurphy.bsky.social · Aug 14

How do they do this? Plts have a unique ‘sponge-like’ structure with lots of surface-connected channels 🧽. We showed they take up DNA-loaded vesicles and ‘membrane free’ DNA fragments by different mechanisms. Once inside, DNA is protected from nuclease degradation! ✂️ 9/19

Lauren Murphy @l-cmurphy.bsky.social · Aug 14

To examine cellular origin, we used WGS and TAPS methylation profiling. Jeanne Inchauspé and ‪‪‪dagams.bsky.social found that plts contain short and long DNA fragments that map to the nuclear genome- mostly leukocyte-derived, with some from hepatocytes- just like cfDNA! 💻 8/19

Lauren Murphy @l-cmurphy.bsky.social · Aug 14

We even analyzed blood from pregnant mums and looked for fragments of the Y-chromosome in their plts – and accurately predicted the sex of their baby in 100% of cases! 🤯👶 7/19

Lauren Murphy @l-cmurphy.bsky.social · Aug 14

Using flow cytometry, ddPCR, and high-resolution imaging we confirmed that plts do indeed take up DNA fragments shed by nucleated cells! In the movie below, a plt (blue) sequesters DNA (labelled in pink) from a nucleated colorectal cancer cell! 🔬6/19

Lauren Murphy @l-cmurphy.bsky.social · Aug 14

So what if they do?! cfDNA analysis is used in antenatal screening and cancer diagnosis. Current methods use plt-depleted plasma, but are limited by the low amount of tumor-cfDNA in early cancer-when screening is v critical. Maybe important info in plts is being missed! 🩸 5/19

Lauren Murphy @l-cmurphy.bsky.social · Aug 14

We were intrigued by prior studies, one from @drkoupenova.bsky.social‬ showing images of plts containing viral DNA and another by
Galit Frydman showing DNA-associated histone proteins. We hypothesized that plts may also sequester endogenous extracellular DNA (cfDNA) as they circulate. 🦠🧬 4/19

Lauren Murphy @l-cmurphy.bsky.social · Aug 14

Platelets (plts) are the smallest and second most abundant cell in our bodies -famous for making blood clots but also important in immunity and cancer biology.

They don’t have their own nucleus. 🙅‍♀️

So why did we go looking for DNA inside of them?!! 🤔😳3/19

Lauren Murphy @l-cmurphy.bsky.social · Aug 14

In this study, we reveal a new function for blood platelets - as ‘sponges’ of DNA from plasma, with important implications for cancer diagnosis and prenatal screening. 🤯🧬 2/19

Lauren Murphy @l-cmurphy.bsky.social · Aug 14

🚨 New paper alert! 🚨 I’m thrilled and proud to share that our latest work has just been published in @science.org! 🎉 🧽

📖 Read our paper here: doi.org/10.1126/sci...

🎬 Watch a summary: youtu.be/MttCA3GGWEM

🧵 Or keep reading for the key points! 🔑 1/19