Thrilled to see a basic mechanistic discovery translate to meaningful clinical benefit! aacrjournals.org/cancerdiscov...

This week, that idea reached patients: Viral-mimicry priming + anti-PD-1 in relapsed/refractory NK/T-cell lymphoma delivered 47.6% complete responses, 66.7% ORR, and ~50% 2-year OS, even after prior PD-1 failure (Huang, Cancer Discovery 2025).

Ten years ago, we discovered that reactivating transposable elements triggers an antiviral state in cancer cells, a process we named viral mimicry, unmasking tumors to the immune system (Roulois, Cell 2015).

We are thrilled to have Daniel De Carvalho (@daniel-decarvalho.bsky.social) from Princess Margaret Cancer Centre / University of Toronto as our Keynote speaker at #EREHD25. What a way to close 3 days of wonderful science. Thank you for being with us in Mexico Daniel!

Today, Gairdner hosted the 2025 Laureate Lectures — a highlight of #GairdnerScienceWeek. All eight laureates shared the stories behind their award-winning science, alongside talks from two Early Career Investigators driving the future of discovery. #GairdnerAwards

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

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

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).

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."

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)

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.

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

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...

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...

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

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

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

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

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.

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.

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.

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.

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

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

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

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...

Happy to see this paper out!

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.

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

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

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

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.

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.