Jonathan Mannion

Incredibly excited to share the 2nd instalment of my PhD work, out today in @ImmunityCP! @MeierLabICR @ICR_London @BreastCancerNow @BCNowPress @CR_UK cell.com/immunity/fullt… A thread, 1/

The FDA approval of vepdegestrant for ESR1-mutant ER+/HER2− advanced breast cancer marks an important milestone for PROTACs! Beyond its importance for patients, this is a landmark validation of targeted protein degradation as a therapeutic modality 👏🏻 fda.gov/drugs/resource…

Check out super cool new paper we contributed to , I’m calling it “"One SNP refolds a lncRNA and rewrites the rules of stem cell self-renewal.” A new lncRNA called HOTSCRAMBL sits in the HOXA cluster and works as a splicing chaperone — it recruits SRSF2 to help HOXA9 get properly spliced in blood stem cells. A common variant (rs17437411) doesn't destroy the RNA, it refolds it, hiding the SRSF2 binding sites. The result: a dysfunctional decoy that can't scaffold splicing, HOXA9 levels drop, stem cells lose self-renewal, and leukemia growth gets constrained. The variant hits harder than a full knockout because the misfolded RNA actively interferes. It's essentially a built-in genetic brake on blood cancer. Read more: kwnsfk27.r.eu-west-1.awstrack.me/L0/https:%2F%2…

What defines human pDC diversity? Our newest work led by @UlezkoAlina in @ImmunityCP uncovers a complex landscape shaped by age and tissue niche, including a cycling pDC subset that declines with age but persists in the BM & expands in malignant BPDCN. shorturl.at/99Zui

Excited to share our discovery of a new programmable RNA-guided DNA-targeting system hiding inside bacteriophages that predates CRISPR. We call it VIPR (Viral Interference Programmable Repeat), and it uses an entirely new logic to find its targets. Thread + link below.

Type 1 IFN primes cross-dressing of cDCs with peptide–MHC-I complexes from non-haematopoietic cells, explaining ability of mRNA vaccines to activate CD8+ T cells against antigens not encoded by the vaccine @Nature @WashU #Murphy nature.com/articles/s4158…

‘Environmentally driven immune imprinting protects against allergy’ nature.com/articles/s4158…

The @GyrdLab uncover an important mechanism by which uORFs prevent over exuberant immunity, inflammation & tissue damage, by buffering the expression of TNFR1, IFNAR1/INFGR2, TLR4 (& mostly likely other receptors) - huge congrats to all authors! science.org/doi/10.1126/sc…

For decades, we taught a simple rule: MHC I → CD8 T cells, MHC II → CD4 T cells. Turns out, that’s incomplete. MHC I doesn’t just help CD8s “see” cells — it also protects cells from CD4 T cell–driven killing.nature.com/articles/s4159…

We’re happy to share our updated manuscript on Ninj1, incorporating measurements of membrane tension, cellular assays of ninj1 and ninj2 dimer stability and MD simulations of ninj1 oligmers opening and forming (see below!). biorxiv.org/content/10.110…

Valiant effort from all Meier lab members and collaborators 👏🏻

Metastasis kills most cancer patients and grows from invisible seeds. How do these seeds escape from attack by immune cells? These seeds harness stress hormones!🤯 ⁦thanks to ⁦@nyscf⁩ ⁦@parkerici⁩ for their support. Today at ⁦@Nature⁩ nature.com/articles/s4158…

Nature research paper: Peripheral immune-inducer dendritic cells drive early-life allergic inflammation go.nature.com/4aKOW4F

When a phase 1 trial is published in @NEJM, you can bet it will be impactful. Here, the p53 reactivator rezatapopt showed an ORR 20% among 77 pts with TP53 mutant (Y220C) advanced tumors. Are we getting closer to drug the most undruggable of all mutations? nejm.org/doi/full/10.10…

Very excited about this review on lung cancer prevention, now a major focus of my lab. Prevention can save lives, reduce suffering, and lower health care costs. Academics are leading this effort, and I hope we can partner with industry to drive it forward. nature.com/articles/s4157…

#ScienceSaturday ❓ Why does immunotherapy work incredibly well for some melanoma patients, but not for others? ➡️ A new study in Cancer Cell takes a closer look at the immune cells that matter most during immunotherapy. Researchers tracked melanoma-specific CD8+ T cells (the immune system’s cancer killers) in patients receiving anti-PD-1 treatment before surgery. ➡️ They found that not all T cells are created equal. Patients who responded best had a special group of T cells marked by a protein called T-bet. These cells weren’t “burned out,” but they weren’t fully fresh either, instead, they were in a powerful in-between state that allowed them to expand, stay active, and attack tumors when PD-1 therapy removed the brakes. ➡️ In contrast, patients who didn’t respond had more terminally exhausted T cells, immune cells that were too worn down to bounce back, even with immunotherapy. ➡️ The team also discovered that these fate decisions start early, in the lymph nodes, before T cells ever reach the tumor. And importantly, ongoing exposure to tumor antigens helped sustain effective immune responses, helping explain why neoadjuvant (pre-surgery) immunotherapy can be so effective. ➡️ Together, these findings show that which T cells are present, not just how many, can predict response to immunotherapy, and could guide better biomarkers and treatment strategies in the future. 🌟 Kudos to the researchers for uncovering how immune cell “identity” shapes success with cancer immunotherapy! @Cancer_Cell @lynn_schuchter @PennMedicine @AmaravadiRavi @PennCancer 🔗 Read more in Cancer Cell: doi.org/10.1016/j.ccel…

Online now: A type I interferon-mitochondrial axis regulates efferocytosis and interferon-stimulated gene induction in macrophages dlvr.it/TQccwZ

@RMedzhitov show that environmental stimuli imprint cross-reactive adapative immune memory that protects against allergy @Nature @YaleMed nature.com/articles/s4158…

Review @NatureCancer @AnGolebiewska @LIH_Luxembourg 🇱🇺 Immunosuppressive mechanisms and therapeutic interventions shaping glioblastoma immunity nature.com/articles/s4301…

💥New paper alert!💥 What’s better than starting 2026 with an @AnnualReviews #Immunology, often a once-in-a-life honor ❤️?! Check it out if you want to know everything about type III interferons #IFN! Thanks to my wonderful team for their amazing work 🤗 doi.org/10.1146/annure…

#WeekendRead! #DendriticCellPower! @reisesousalab Lim &co show @NatImmunol that cDC1s exploit DNGR1 to crosspresent #tumor #neoantigens derived from F-actin binding proteins protecting against tumorigenesis but favoring cancer immunoediting! nature.com/articles/s4159…