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Posts by Jonathan Kagan



How important do you feel discovery research and ‘basic’ science is for understanding disease?

Well, I have a little bit of a biased view on the topic, since I'm a basic scientist myself. The lab has made more and more discoveries with very strong therapeutic implications, and often people ask me why we are not pursuing these further ourselves. Part of it is that I think about this very much as an ecosystem. People have different skills – I have colleagues who are very good at the application side of things and I have other colleagues, including people in my lab, who are very good at the basic science. There are a lot of very smart people at every stage in the ecosystem and, sometimes, we have to acknowledge that we can't all be experts in every step. A lot of basic science discoveries will end up having profound implications in the clinic – if you don't have the full imagination about how to get it there, that's okay, because you're still a very important piece of the jigsaw puzzle and other people can help. If the basic science discoveries didn't exist, then it's quite possible that the well would run dry. We cannot simply rely on the idea that the therapies currently in clinical trials are going to be enough because we already know that – for diseases, such as cancer, and with rapidly evolving viruses – there needs to be a constant influx of new ideas to stay ahead of the arms race. I'd also make a plug for the fact that, ultimately, we are all interested in human disease, but disease research in humans is not ethical or possible. This is why creating and studying model organisms in a high-throughput, low-investment context is incredibly important. We cannot just say ‘okay, we're going to stop work on anything that is not related to human research’, because – actually – it's all relevant to humans.

How important do you feel discovery research and ‘basic’ science is for understanding disease? Well, I have a little bit of a biased view on the topic, since I'm a basic scientist myself. The lab has made more and more discoveries with very strong therapeutic implications, and often people ask me why we are not pursuing these further ourselves. Part of it is that I think about this very much as an ecosystem. People have different skills – I have colleagues who are very good at the application side of things and I have other colleagues, including people in my lab, who are very good at the basic science. There are a lot of very smart people at every stage in the ecosystem and, sometimes, we have to acknowledge that we can't all be experts in every step. A lot of basic science discoveries will end up having profound implications in the clinic – if you don't have the full imagination about how to get it there, that's okay, because you're still a very important piece of the jigsaw puzzle and other people can help. If the basic science discoveries didn't exist, then it's quite possible that the well would run dry. We cannot simply rely on the idea that the therapies currently in clinical trials are going to be enough because we already know that – for diseases, such as cancer, and with rapidly evolving viruses – there needs to be a constant influx of new ideas to stay ahead of the arms race. I'd also make a plug for the fact that, ultimately, we are all interested in human disease, but disease research in humans is not ethical or possible. This is why creating and studying model organisms in a high-throughput, low-investment context is incredibly important. We cannot just say ‘okay, we're going to stop work on anything that is not related to human research’, because – actually – it's all relevant to humans.



Do you think basic science is particularly threatened by cuts to funding?

Science itself is quite uncertain. We do experiments wondering if they will even work. It's discovery, and you don't know where it's going to lead. It could lead to a billion-dollar company, something like mRNA vaccines or CRISPR-Cas9 gene editing, or it could simply be something that interests you. Sometimes it might appear esoteric from the outside, but there are very smart people dedicated to this work. We shouldn't lose sight of the fact that most of this work is paid for by taxpayers, but funding uncertainty creates a very unstable foundation. If the foundations are weak, people are going to get much more conservative about the science that they're doing and worry that ‘blue-skies research’ is not worth pursuing because it won't get funded. And that would be a mistake because all innovation in science really originates from blue-skies, basic research. The second thing that uncertainty does is send a message to our young trainees – who are our future – that this is not a career option that will provide professional and personal stability. I worry that this kind of uncertainty will mean we lose an entire generation of people, and that would be a loss we might not be able to overcome.

Do you think basic science is particularly threatened by cuts to funding? Science itself is quite uncertain. We do experiments wondering if they will even work. It's discovery, and you don't know where it's going to lead. It could lead to a billion-dollar company, something like mRNA vaccines or CRISPR-Cas9 gene editing, or it could simply be something that interests you. Sometimes it might appear esoteric from the outside, but there are very smart people dedicated to this work. We shouldn't lose sight of the fact that most of this work is paid for by taxpayers, but funding uncertainty creates a very unstable foundation. If the foundations are weak, people are going to get much more conservative about the science that they're doing and worry that ‘blue-skies research’ is not worth pursuing because it won't get funded. And that would be a mistake because all innovation in science really originates from blue-skies, basic research. The second thing that uncertainty does is send a message to our young trainees – who are our future – that this is not a career option that will provide professional and personal stability. I worry that this kind of uncertainty will mean we lose an entire generation of people, and that would be a loss we might not be able to overcome.

I was interviewed by @katiepickup.bsky.social recently for @dmmjournal.bsky.social. This has a little bit of my background, a little bit on science and mentoring, and a little bit (ok, more than a little bit) on funding in science.

Check it out at: journals.biologists.com/dmm/article/...

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Highly recommend!

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Co‐Culture Systems to Study Epithelial‐Immune Interactions During SARS‐CoV‐2 Infection Robust inflammatory responses to viral infection are mediated by immune cell populations, including monocytes and dendritic cells. However, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2...

I've gotten lots of questions about our co-culture systems to study epithelial-immune interactions in viral infections, so wrote a step-by-step guide! I hope this will help anyone looking to adapt these protocols for their research.
currentprotocols.onlinelibrary.wiley.com/doi/abs/10.1...

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Clinical development of cancer vaccines - Nature Medicine This Review highlights insights from recent clinical trials and discusses critical factors for optimizing cancer vaccines, with a focus on proxies for vaccine efficacy, neoantigen selection, modular p...

Want to know how cancer vaccines can keep you alive?
Very pleased to join several luminaries in the field to offer a comprehensive review on this important topic.
@harvardmed.bsky.social @bostonchildrens.bsky.social #cancer #vaccine
www.nature.com/articles/s41...

1 month ago 10 5 0 0
Poster of the 2026 CSHA meeting on Bacterial Infection & Host Defense.

Poster of the 2026 CSHA meeting on Bacterial Infection & Host Defense.

Please join us for the Cold Spring Harbor Asia @cshlnews.bsky.social meeting on Bacterial Infection & Host Defense this May 11-15 in Suzhou, China! We have a fantastic lineup of speakers. Abstract deadline is March 6. Hope to see you there!

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STING-dependent translation inhibition restricts RNA virus replication | PNAS In mammalian cells, IFN responses that occur during RNA and DNA virus infections are activated by distinct signaling pathways. The RIG-I–like-recep...

For additional reading on this topic:
www.pnas.org/doi/10.1073/...

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STING–NF-κB signaling builds an influenza spillover barrier Influenza pandemics are often traced back to the spillover of avian influenza A viruses (IAVs) to humans. However, barriers against IAV transmission remain elusive. We demonstrated human stimulator of...

Increasing evidence that STING has functions beyond DNA viruses. A new study reports that STING restricts influenza infection, independently of IFN. This work complements prior studies that STING prevents infection with diverse RNA viruses.
www.science.org/doi/10.1126/...

1 month ago 12 2 1 0
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Innate Immunity: Diversity in Host Defense and Disease | Keystone Symposia Join us at the Keystone Symposia on Innate Immunity: Diversity in Host Defense and Disease, March 2026, in Banff, with field leaders!

Poster deadline is approaching for @keystoneSymposia.bsky.social #InnateImmunity: Diversity in #HostDefense & Disease, this March in Banff! See scholarship, abstract and registration: keysym.us/KSInnateImmune26 #KSInnateImmune26 @jkagan1.bsky.social @brozlab.bsky.social

2 months ago 3 1 0 1
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Caspase-4 binds to LPS membranes with positive curvature for non-canonical inflammasome activation The cytosolic LPS sensor caspase-4 controls antibacterial immunity by inducing pyroptosis and cytokine secretion. Began et al. show how remodeling of LPS membranes by interferon-induced GTPase GBP1 pr...

PAPER ALERT!
I am excited to share that our study describing the molecular mechanism of caspase-4 activation has just been published in Immunity.
www.cell.com/immunity/ful...

I would like to thank all the co-authors for their valuable contributions.
Well done guys!
Link for short summary below👇

2 months ago 28 7 3 1
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On the balance of knowledge - Nature Reviews Immunology Ruslan Medzhitov shares his thoughts on the balance between generating data and developing theories in immunology, with a focus on exploring the rules that govern complex systems.

Too much data, too little thinking.
A important essay from Ruslan Medzhitov on the importance of understanding data, not just generating it. A must read.
@Yale
www.nature.com/articles/s41...

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🌟 Congratulations to the 2026 Class of Distinguished Fellows of AAI (DFAAI)!

From groundbreaking research to dedicated service, these members represent the pinnacle of the immunology field. Check out this year’s honorees: https://bit.ly/DFAAI2026

#DFAAI #Immunology #ScienceExcellence

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Innate Immunity Meeting Promo
Innate Immunity Meeting Promo YouTube video by KeystoneSymposia

A fantastic innate immunity conference coming soon. Join us!
youtu.be/xmQv36uYm7s?...

2 months ago 1 1 0 0
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Scientific Editor, Cell Cell has an opening for a full-time scientific editor. If you are a passionate, mission-driven team player who loves thinking broadly about science and wants to have a positive impact, we invite you t...

Cell is hiring!

Do you have a background in #neuroscience or #immunology? Better still, #neuroimmunology? Cell has an opening for a full-time scientific editor. Role will be based out of any one of our offices in Medford, MA, UK, Spain, Netherlands, China tinyurl.com/4ma236xn @cp-cell.bsky.social

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Hallmarks of cancer—Then and now, and beyond Hanahan revisits the evolving framework of cancer hallmarks, synthesizing 25 years of conceptual refinement into a multidimensional view of tumor biology. This review highlights how aberrant capabilit...

Today at Cell: A new #HallmarksofCancer review by Doug Hanahan: www.cell.com/cell/fulltex...
This review marks 25 years since the original seminal Cell review by Hanahan & Robert Weinberg and its impactful follow up in 2011.
@cp-cell.bsky.social @cellpress.bsky.social

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🎓 Early-career scientists - don’t miss out! Register by Jan 21 (11:59 PM MST) for the joint Keystone Symposia on Innate Immunity & Aging. Save $250 and attend two meetings for the price of one.

🔗 keysym.us/KSInnateImmu...
🔗 keysym.us/KSAging26

@jkagan1.bsky.social
#KSInnateImmune26 #KSAging26

3 months ago 4 2 0 0
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Dealing with ScienCV formatting Some tips for composing and making your new NIH biosketch not look like garbage

Been hearing some horrifying chatter about dealing with the new #NIH common form and #ScienCV system, so I put together a short video with some tricks for mitigating some of those pain points.

Hope it helps? 🧪

open.substack.com/pub/emptymod...

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What goes into planning the world's largest all-immunology event? Join AAI President Dr. Uli von Andrian and Program Chair Dr. Shekhar Pasare for a preview of #IMMUNOLOGY2026™!

🧬 Presidential Symposium
🔬 Special Sessions
🎓 Trainee Programs

🔗 immunology2026.aai.org

3 months ago 5 4 0 0
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In vivo detection of immune responses via cytokine activity labeling While much is known about the identity and regulation of cytokine-producing cells, the cell types that respond to cytokines remain largely uncharacter…

#CyclopsPower👁️ Lu, Choi, Huh &co describe @cp-cell.bsky.social a new reporter system to detect cells that respond to a cytokine & utilize it to identify ileal epithelial cells that respond to IL17 or IFNg responsive CD8 T cell within tumors which are hypofunctional!

3 months ago 11 2 0 0

A must read! Highly recommend.

3 months ago 4 1 0 0
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Molecular, Cellular, Tissue, and Organismal Functions of Type III Interferons Type III interferons are essential immune mediators playing pleiotropic roles during health and disease. In this review, we highlight the molecular and cellular pathways that lead to the production of...

💥New paper alert!💥 What’s better than starting 2026 with an @annualreviews.bsky.social #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/annu...

3 months ago 57 21 1 0
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Innate Immunity: Diversity in Host Defense and Disease | Keystone Symposia Join us at the Keystone Symposia on Innate Immunity: Diversity in Host Defense and Disease, March 2026, in Banff, with field leaders!

Working with a great team to organize @keystoneSymposia.bsky.social #InnateImmunity : Diversity in #HostDefense & Disease, this March! Join us to explore emerging research in Banff! keysym.us/KSInnateImmune26 #KSInnateImmune26

3 months ago 12 5 0 0
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LPS binding caspase activation and recruitment domains (CARDs) are bipartite lipid binding modules A bacterial sensory protein detects self- and nonself-lipids by similar mechanisms.

Article on the discovery of how LPS is detected by caspase-11.

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

3 months ago 1 0 0 0
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Cracking the Code of Immunity Immunologists have long studied how our body fights pathogens, but the precise patterns of molecules required to trigger an immune response weren’t fully understood. As a PhD student, Anh Cao took the...

Harvard profiles the discovery of how inflammatory caspases detect bacterial infection. And how our own lipids bind caspases in the same manner.

Kudos to Anh Cao, who made these discoveries.
@harvardmed.bsky.social @harvard.edu

gsas.harvard.edu/news/crackin...

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www.forbes.com/sites/johnwe...

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MOLECULAR DEFINITION OF THE ENDOGENOUS TOLL-LIKE RECEPTOR SIGNALING PATHWAY
MOLECULAR DEFINITION OF THE ENDOGENOUS TOLL-LIKE RECEPTOR SIGNALING PATHWAY YouTube video by HFSP

1/2: YouTube knows what I was up to last summer:
www.youtube.com/watch?v=UV7r...

Many thanks again to @hfspo.bsky.social for inviting me to the Awardees Meeting in Melbourne this July 😁

3 months ago 3 1 2 0

Many congrats on this recognition for your outstanding work. Can't wait to learn what you discover next!

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Correction of age-associated defects in dendritic cells enables CD4+ T cells to eradicate tumors Adjuvants known as hyperactivators can correct age-associated defects in dendritic cells, enabling anti-tumor T cell responses in old and young mice. The protective immunity elicited by hyperactive de...

For additional reading: Original study describing how NLRP3-stimulatory vaccines induce CD4 T cell mediated anti-tumor immunity.
www.cell.com/cell/fulltex...

4 months ago 1 0 0 0
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CD27 agonism enhances long-lived CD4 T cell vaccine responses critical for antitumor immunity CD27 agonism enhances vaccine-induced CD4 T cell responses, enabling durable antitumor immunity not entirely dependent on CD8 T cells.

Evidence continues to accumulate that CD4 T cells are important for vaccine induced anti-tumor immunity. A new study links CD27 to the generation of long-lived protective CD4 T cells. Kudos to the authors on this exciting finding.

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

4 months ago 5 0 1 0
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#Evavold Lab 2025 Holiday memories.

It's been a challenging year, but these hurdles led to many scientific and personal reasons to celebrate.

Macrophage Interest Group with Garris lab and Prof. Eric Dang!

@ragoninstitute.bsky.social @harvardmed.bsky.social @massgeneralbrigham.bsky.social

4 months ago 6 1 1 0
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Human gut M cells resemble dendritic cells and present gluten antigen - Nature An intestinal organoid model recapitulates human microfold (M) cell function and transcriptomic profiling and biochemical assays demonstrate that M cells uptake and present antigens to the immune syst...

#WeekendRead! #EveryCellIsAnImmuneCell! #MysterySolved! Clevers &co reveal @nature the differentiation trajectory of human intestinal M cells & show they respond to GM-CSF, express PRRs, & present antigen via MHC-II as dendritic cells, contributing to anti-gluten responses!
doi.org/10.1038/s415...

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