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Daniel De Carvalho @daniel-decarvalho.bsky.social · 12d

It was great to collaborate with brilliant colleagues and friends on this multidisciplinary project, combining evolutionary modeling, statistical physics, immunology, and wet-lab validation

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Daniel De Carvalho @daniel-decarvalho.bsky.social · 12d

Today’s paper reframes repeat activation from "noise" to a conserved immunogenic signal, explaining why therapies derepressing repeats prime anti-tumor immunity and why tumors develop countermeasures. We believe viral mimicry escape is necessary during cancer initiation and thus a cancer hallmark

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Daniel De Carvalho @daniel-decarvalho.bsky.social · 12d

Cancers usually adapt this viral mimicry pressure. p53 loss leads to chronic mimicry and tolerance in HGSOC (Ishak, Cancer Discovery 2025), PDAC relies on LINE-1 ORF1p subverting sensing (Sun, Immunity 2024), while other use ADAR1/XRN1 (Mehdipour, Nature 2020; Hosseini, Cell Reports 2024).

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Daniel De Carvalho @daniel-decarvalho.bsky.social · 12d

A decade ago, we showed that DNA demethylation induces repeat transcripts, triggering an antiviral state that selectively kills cancer cells, termed viral mimicry (Roulois, Cell 2015). Today's work helps to explain why repeats often appear "viral."

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Daniel De Carvalho @daniel-decarvalho.bsky.social · 12d

2) Organism-centric: PAMPs act as a cell-intrinsic alarm for transcriptional dysregulation, retained to help organisms detect and correct errors. We call this ‘the fire alarm hypothesis’ (Lindholm, Trends in Cancer 2023)

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Daniel De Carvalho @daniel-decarvalho.bsky.social · 12d

This enabled us to score the immunogenicity of different repeats across species and led to two non-exclusive evolutionary hypotheses: 1) Repeat-centric: PAMP-like motifs support the repeat lifecycle.

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Daniel De Carvalho @daniel-decarvalho.bsky.social · 12d

We found that many transposons resemble pathogens to innate immune sensors, a property widespread across eukaryotes. Here, we formalized "viral mimicry" with a quantitative statistical physics framework, estimating selective forces that enrich pathogen-associated motifs beyond the genome background

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Daniel De Carvalho @daniel-decarvalho.bsky.social · 12d

Excited to have this paper out today!

Repeats mimic pathogen-associated patterns across a vast evolutionary landscape."

It was a fun and productive collaboration with Benjamin Greenbaum John LaCava, Simona Cocco, Petr Šulc and many others!

www.cell.com/cell-genomic...

Repeats mimic pathogen-associated patterns across a vast evolutionary landscape

An emerging hallmark of disease is transcription of pathogen-associated molecular patterns from within the genome–known as viral mimicry. We propose a statistical physics framework to measure “selecti...

www.cell.com

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Reposted by Daniel De Carvalho

Fusion Conferences @fusionconf.bsky.social · Jul 17

Are you currently in the ERE related field & want to find new collaborative opportunities? Join our Chairs @chiappinellilab.bsky.social, @shenhui1986.bsky.social, Ting & Tao at #EREHD25 this Nov!
🎙️Talk Submission extended to 03 Sept
💰Final few $500 grants remaining
Don't Miss out! bit.ly/4eRq9Mp

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Reposted by Daniel De Carvalho

Fusion Conferences @fusionconf.bsky.social · Jun 4

Don't forget to register for #EREHD25! Our talk submission deadline has been extended to 12 JUNE 2025, so submit your abstract today to join our incredible speaker line up in Mexico this November 🏖️☀️
🔗 bit.ly/4kHWbw0

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Daniel De Carvalho @daniel-decarvalho.bsky.social · Apr 18

read more here: www.science.org/content/arti...

Could blocking ‘jumping genes’ help fight disease and aging?

The first clinical trials are testing inhibitors of transposons, DNA sequences that hop around the genome on their own

www.science.org

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Daniel De Carvalho @daniel-decarvalho.bsky.social · Apr 18

They’re not just passive genomic elements—they’re active players that may hold the key to new therapies.

Exciting to see the field gaining attention and momentum.

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Daniel De Carvalho @daniel-decarvalho.bsky.social · Apr 18

Over the past decade, retroelements have become one of the hottest topics in biomedical science, shedding light on evolution, aging, cancer, autoimmunity, neurodegeneration, and more.

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Daniel De Carvalho @daniel-decarvalho.bsky.social · Apr 18

Risky moves: Can blocking “jumping genes” treat diseases and aging?

Great piece in Science Magazine highlighting recent efforts to understand and target transposons—also known as "jumping genes"—in human disease and aging.

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Daniel De Carvalho @daniel-decarvalho.bsky.social · Apr 15

Thank you @gairdnerawards.bsky.social! I'm truly humbled and grateful for this recognition. Science is never a solo journey and this award reflects the hard work, creativity, and persistence of many amazing scientists I had the privilege to work with.

The Gairdner Foundation @gairdnerawards.bsky.social · Apr 11

Congratulations to the 2025 Canada Gairdner Award laureates! This year’s laureates represent some of the world’s most significant biomedical and global health research and discoveries.

Learn more about their award-winning research here: gairdner.org/resource-hub...

#GairdnerAwards

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Reposted by Daniel De Carvalho

André Picard @picardonhealth @picardonhealth.bsky.social · Apr 11

The brain trust with a difference: 2025 Gairdner award winners have taken big strides in the U.S., at a time when Trump-era cuts cast doubt on the future, by @ivansemeniuk.bsky.social @jenniferyang.bsky.social www.theglobeandmail.com/canada/artic...
@theglobeandmail.com @gairdnerawards.bsky.social

In a time of despair for U.S. scientists, Gairdner Award winners shine brighter than usual

The winners of this year’s Canadian science prizes are all based in the United States, where Trump-era cutbacks to research and medical regulation have sown doubt in the future

www.theglobeandmail.com

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Reposted by Daniel De Carvalho

The Gairdner Foundation @gairdnerawards.bsky.social · Apr 11

Congratulations to the 2025 Canada Gairdner Award laureates! This year’s laureates represent some of the world’s most significant biomedical and global health research and discoveries.

Learn more about their award-winning research here: gairdner.org/resource-hub...

#GairdnerAwards

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Reposted by Daniel De Carvalho

Princess Margaret Cancer Centre @pmresearch-uhn.bsky.social · Mar 17

New Links: Cancer and Immune Evasion

Cancer cells without the tumor suppressor protein p53 become more resistant to the body's immune response and more likely to survive. A study led by Dr. Daniel De Carvalho at UHN’s Princess Margaret Cancer Centre.

www.uhnresearch.ca/news/new-lin...

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Daniel De Carvalho @daniel-decarvalho.bsky.social · Feb 25

Happy to see this paper out!

Research at UHN @uhnresearch.ca · Feb 25

Scientists @pmresearch-uhn.bsky.social have uncovered how cancer can evade immune defenses after losing a key tumour-suppressing gene. These findings implicate repetitive elements in DNA and may unlock new targets for cancer interception.

Read more ➡️ www.uhnresearch.ca/news/new-lin...

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Daniel De Carvalho @daniel-decarvalho.bsky.social · Jan 17

We observers that we can interfere with this process, for example by blocking the reverse transcriptase activity of LINE1, suggesting a promising avenue for early cancer interception.

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Daniel De Carvalho @daniel-decarvalho.bsky.social · Jan 17

This chronic viral mimicry activation increases cellular tolerance of cytosolic nucleic acids and diminishes cellular immunogenicity. Moreover, this viral mimicry conditioning promotes adaptive immune evasion

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Daniel De Carvalho @daniel-decarvalho.bsky.social · Jan 17

Back to the recent cancer Discovery paper. We observed in premalignant lesions of the fallopian tube and in syngeneic epithelial ovarian cancer models that loss of p53 permits transcription of immunogenic repetitive elements and chronic viral mimicry activation

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Daniel De Carvalho @daniel-decarvalho.bsky.social · Jan 17

For more on this fire alarm hypothesis, see our latest review: t.co/MBha505aOH

https://www.cell.com/trends/cancer/abstract/S2405-8033(22)00191-1

t.co

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Daniel De Carvalho @daniel-decarvalho.bsky.social · Jan 17

We believe that transcription of repetitive elements is a cost that cancer cells need to pay in order to undergo the epigenetic reprogramming necessary for transformation and that viral mimicry works as a fire alarm to cull transformation.

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Daniel De Carvalho @daniel-decarvalho.bsky.social · Jan 17

Over the years, we and several other groups have shown that transcription of immunogenic repetitive elements can induce tumor suppressive ‘viral mimicry’ responses. Paradoxically, malignant transformation is frequently associated with transcription of repetitive elements.

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