International Course of Immunotherapy March 23-25, 2026 11th Edition Theme: Targeting Immune Aging | Time: 9:00am-1.15pm NYC; 14:00-18.15h Paris; 10:00am-2.15pm Sao Paulo

At Immunoschool, @gitlinlabmsk.bsky.social will show how VEXAS syndrome is reshaping our understanding of immune aging, late-onset inflammatory disease & new routes to immunotherapy. A powerful 🔗 between clonal hematopoiesis & systemic inflammation.

Register FREE: www.eventbrite.com/e/internatio...

Congrats Ryan!!

NY medical schools press Gov. Hochul to put up billions for scientific research The request comes amid continuing uncertainty over federal funding, with research and thousands of jobs on the line.

NYers helps us call on @governor.ny.gov to invest in the Empire Biomedical Research Institute. A robust, stable research ecosystem protects jobs, fuels innovation, and builds community health. NY must invest in our global leadership in science. nycures.org @gothamist.com: tinyurl.com/5fab5k7u

Thanks Pedro!!!

🚨Thrilled to share our latest work, published online today
@nature.com in which we decipher mechanisms underlying the enigmatic VEXAS syndrome - a huge team effort
@mskcancercenter.bsky.social led by superstars Varun Narendra + @tandriladas.bsky.social 1/

www.nature.com/articles/s41...

Independent mechanisms of inflammation and myeloid bias in VEXAS syndrome @nature.com @gitlinlabmsk.bsky.social
@mskcancercenter.bsky.social
www.nature.com/articles/s41...

MSK Researchers Make Strides Against VEXAS Syndrome VEXAS syndrome is an a confounding adult-onset inflammatory disease first described in 2020, which affects 1 in 4,000 men over 50. Now, MSK researchers are shedding new light on its mechanisms and lay...

Also thanks to Ian Demsky @mskcancercenter.bsky.social for this fantastic article on our paper:

www.mskcc.org/news/msk-res...

Elisa de Stanchina and her amazing team, key collaborators in
@caleblareau.bsky.social and @lowelab.bsky.social
and support from funders at NIH, Burroughs Wellcome Fund, Ludwig Center at MSK, @cycleforsurvival.bsky.social
@wcm-imp.bsky.social
@mskcancercenter.bsky.social
- THANK YOU ALL! 13/

It's been an absolute whirlwind working on this project from start to finish and a ton of fun! So many people to thank including Linsey Wierciszewski, Pia Martindale (who both started my lab with me in 2022!), Rebecca Londoner, @joshuakmorrison.bsky.social, Yuzu Kanno, Alek Casiano,... 12/

And finally, molecularly, this cell death phenotype correlated with a marked kinetic defect in the Lys63/Linear polyubiquitylation of inflammatory signaling complexes, linking VEXAS with other rarer germline disorders affecting LUBAC, OTULIN, etc 11/

Secondly, Uba1 M41T mutation either in mouse or human HSPCs triggered a pronounced myeloid bias and an unfolded protein response, as described in the initial NEJM report - notably, this was independent of cell death as it still occurred in RIPK3-Casp8 deficient mutant cells 10/

First, we found that across all mutation types tested (M41T, M41V, splice site mutants), Uba1 mutant macrophages showed aberrant apoptotic and necroptotic responses to stimulation with inflammatory triggers like TNF and LPS - through the RIPK3-MLKL-Casp8 axis. 9/

This worked surprisingly well in pools of primary macrophages and we even saw the VEXAS-like diminution of UBA1b and expression of UBA1c, so we were off to the races to try to figure out what was happening molecularly/cellularly. 8/

So, we ultimately recreated Uba1 M41T, M41V, and splice site mutations (which happen to lead to a mis-splicing event that skips Met41) in primary mouse macrophages as well as M41T mutations mouse HSPCs, human monocytes and HSPCs! 7/

But how do you connect UBA1 mutations to this severe autoinflammatory phenotype? This is where Varun and @tandriladas.bsky.social stepped in. The first key step was developing robust genetic models. 6/

Strikingly, Beck et al found that these somatic mutations occurred in hematopoietic stem/progenitor cells (HSPCs) and their myeloid, but not lymphoid, progeny - leading to progressive bone marrow failure and severe multiorgan autoinflammation. 5/

So what are these mutations? Beautiful work from Beck et al in the NEJM paper showed Met41 mutations selectively impair translation initiation that normally generates the UBA1b isoform, leading to aberrant initiation at Met67 instead - generating an impaired isoform, UBA1c. 4/

Estimated Prevalence and Clinical Manifestations of UBA1 Variants Associated With VEXAS Syndrome in a Clinical Population - PubMed This study provides an estimate of the prevalence and a description of the clinical manifestations of UBA1 variants associated with VEXAS syndrome within a single regional health system in the US. Additional studies are needed in unselected and genetically diverse populations to better define genera …

Fast forward several years, and what's emerged is that this unusual disease termed VEXAS syndrome for its cardinal features has an estimated prevalence as high as ~1 in 4,000 males over 50 3/

pubmed.ncbi.nlm.nih.gov/36692560/

Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease - PubMed Using a genotype-driven approach, we identified a disorder that connects seemingly unrelated adult-onset inflammatory syndromes. We named this disorder the VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. (Funded by the NIH Intramural Research Programs and the EU Horizon 20 …

The story begins in Dec 2020, when a group at NIH
discovered somatic mutations in UBA1 - initially all at Met41 - in 25 patients with an undiagnosed inflammatory/hematologic disorder. A real shock as UBA1 is the major E1 enzyme in the ubiquitylation cascade! 2/

pubmed.ncbi.nlm.nih.gov/33108101/

🚨Thrilled to share our latest work, published online today
@nature.com in which we decipher mechanisms underlying the enigmatic VEXAS syndrome - a huge team effort
@mskcancercenter.bsky.social led by superstars Varun Narendra + @tandriladas.bsky.social 1/

www.nature.com/articles/s41...

Congratulations to IMP faculty members Chryssie Brown @chrysothemisbrown.bsky.social and Alex Gitlin @gitlinlabmsk.bsky.social on receiving the 2025 Pershing Square Prize!! 🎉

G-quadruplex–stalled eukaryotic replisome structure reveals helical inchworm DNA translocation DNA G-quadruplexes (G4s) are non–B-form DNA secondary structures that threaten genome stability by impeding DNA replication. To elucidate how G4s induce replication fork arrest, we characterized fork ...

How do replisomes walk on DNA? And what happens when they run into a G-quadruplex? @sahilbatra.bsky.social and @benallwein.bsky.social provide unexpected insight in our latest paper with Richard Hite @mskcancercenter.bsky.social @science.org www.science.org/doi/10.1126/.... Congrats to all authors!

Splenic TNF-α signaling potentiates the innate-to-adaptive transition of antiviral NK cells NK cells possess innate and adaptive features, but unlike T and B cells, NK cells are not thought to require priming in lymphoid organs. Mujal et al. demonstrate that the spleen supports enhanced expa...

Congratulations to Dr. Adriana Mujal on this @cp-immunity.bsky.social study demonstrating a new role for an age old cytokine! www.cell.com/immunity/ful...

A figure showing a model for using BCR and TCR sequences to classify immunological disorders.

Attempting to read the language of B cell and T cell receptor sequences to diagnose immunological diseases:
Our new paper, led by the outstanding Maxim Zaslavsky @maximzaslavsky.bsky.social sky.bsky.social with help from me and Anshul Kundaje @anshulkundaje.bsky.social.
Link: buff.ly/3QvxSVf

Deep thanks to our many collaborators and all research participants. #immunology #science 🧪 @science.org @sarahhross.bsky.social

NIH funding was the lifeblood of this work, as it is for almost all biomedical discoveries and therapies in the U.S. @niaidnews.bsky.social

Hi everyone! Our team, the Cell Cyclers, are raising funds this year as part of #cycleforsurvival to support rare cancer research. 100% of donations will go to @mskcancercenter.bsky.social for this cause and are being matched dollar for dollar today! 🙏To donate:
secure2.convio.net/mskcc/site/T...

I’m proud to join more than 30 colleagues today in sharing our analysis of potential risks from “mirror life”. We summarize our findings in a @science.org article, and in greater detail in a 300pg technical report:

Article: www.science.org/doi/10.1126/...
Report: purl.stanford.edu/cv716pj4036

Regulation of human interferon signaling by transposon exonization Transposable element exonization can yield functional protein isoforms as seen for primate-specific IFNAR2.

I’m excited to share our latest study led by @giuliapasquesi.bsky.social out today in @cellpress.bsky.social , uncovering a new way transposons have been repurposed for human interferon signaling! Read on for a thread on cryptic splice variants, decoy receptors, and viruses (1/N) 👇🧵 #TESky 🧪

Join the BCMB PhD program jointly run by Weill Cornell Medicine and Memorial Sloan Kettering Cancer Center. Deadline December 1st, 2024.

If you are interested in pursuing a PhD in biomedical sciences in New York City, it is still time to apply to the BCMB program run jointly by Weill Cornell Medicine and Memorial Sloan Kettering Cancer Center ! Deadline: Dec 1, 2024.

Specific tRNAs promote mRNA decay by recruiting the CCR4-NOT complex to translating ribosomes The CCR4-NOT complex is a major regulator of eukaryotic messenger RNA (mRNA) stability. Slow decoding during translation promotes association of CCR4-NOT with ribosomes, accelerating mRNA degradation....

This is a very cool paper that I will add to my Mol Bio course. Specific tRNA recruitment of mRNA degradation complex to ribosome through the P site tRNA interactions with CCR4-NOT complex 1/ www.science.org/doi/10.1126/...