Mikel Haggadone, PhD

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!

I'm excited to share that the Auditory Systems Gordon Research Seminar is accepting abstracts! This year's GRS will be July 18-19 in Easton, MA. The GRS is an amazing opportunity for trainees to share their work and network with other colleagues in the field. Apply here: www.grc.org/auditory-sys...

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NHLBI has not funded a single new R01 in FY2026 which began almost 5 months ago

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👇

Online now: Caspase-4 binds to LPS membranes with positive curvature for non-canonical inflammasome activation

Aerobic glycolysis promotes NLRP3 inflammasome activation via NLRP3 lactylation Liu et al. reveal that lactate, an aerobic glycolysis product, promotes NLRP3 inflammasome activation and pyroptosis. NLRP3 is identified as a target of lactylation, and K24 and K565 have potential to...

#WeekendRead! #ImmunometabolismPower! #InflammasomePower! Liu, Yin &co show @cp-cellchembiol that lactate downstream of aerobic glycolysis is used to directly lactylates NLRP3 increasing ASC recruitment and inflammasome activation, which exacerbates lethality in sepsis! www.cell.com/cell-chemica...

My nonprofit @your.neighborhoodscientist.org is looking for scientists to share their stories with us in 2026! Is your New Year's resolution to communicate & interface more with your community as a scientist? Send us a pitch at audrey@neighborhoodscientist.org ! 🧪🧠🇺🇸

Suhas Bobba holding the ASM Infection and Immunity Poster Award certificate at the Midwinter Conference of Immunologists

Congratulations to my
& @brodskyigorlab.bsky.social’s joint postdoc Suhas Bobba on receiving the @asm.org Infection & Immunity Poster Award for his work on innate immune control of intestinal Yersinia infection at the Midwinter Conference of Immunologists @midwinter-immun.bsky.social!

I had a wonderful time at Midwinter Immunology & was honored to receive the Ray Owen Poster Award after an awesome presentation by @sunnyshinlab.bsky.social!

2026 was my first time attending — definitely won’t be my last! Thank you to @brodskyigorlab.bsky.social & co. for an amazing meeting! 🙏

Thank you so much for bringing me into the world of mRNA translation!! It’s been such a joy to learn and apply! 🙏

Excited to share our new pre-print on the control of NLRP3 inflammasome assembly and ASC translation dynamics by environmental amino acids. A true team science effort: our phenomenal partners @mikelhaggadone.bsky.social & @sunnyshinlab.bsky.social working with Brian Goldspiel 🙏

@biorxivpreprint.bsky.social Environmental Amino Acid Sensing Regulates the Rate of ASC Translation and NLRP3 Inflammasome Assembly @briangoldspiel.bsky.social @mikelhaggadone.bsky.social
@sunnyshinlab.bsky.social @pennmicro.bsky.social @metabailism.bsky.social
www.biorxiv.org/content/10.6...

Congrats @sunnyshinlab.bsky.social and colleagues on this super cool and intriguing story on the role of dietary amino acids in regulating NLRP3 inflammasome activation by controlling translation of the ASC adapter! 🤯🙌🏼

Thank you so much, Igor! So appreciate your feedback and support along the way! 🙏

Congrats @mikelhaggadone.bsky.social on this beautiful work. So excited to see the preprint out!

Thrilled to share our new preprint showing that dietary amino acids license the NLRP3 inflammasome via mTOR-dependent mRNA translation! Congrats to co-1st authors @mikelhaggadone.bsky.social, Brian Goldspiel, co-senior author @metabailism.bsky.social & collaborators! www.biorxiv.org/content/10.6...

Nucleotide metabolic rewiring enables NLRP3 inflammasome hyperactivation in obesity Obesity is a major disease risk factor due to obesity-associated hyperinflammation. We found that obesity induced Nod-like receptor pyrin domain–containing 3 (NLRP3) inflammasome hyperactivation and e...

Why is obesity often associated with dysregulated, low-grade chronic inflammation?
In our new paper in @science.org we show that obesity rewires nucleotide metabolism in immune cells, making inflammatory responses much easier to trigger. www.science.org/doi/10.1126/...

This project has been the most fulfilling & intellectually challenging of my life—I’m deeply grateful to the mentors & collaborators who made it possible. We look forward to receiving feedback from the field as we continue improving & moving it toward publication. 🙏

We postulate that this burst in ASC translation acts as a filamentation seed that more rapidly tips the cell toward speck crystallization when NLRP3 is triggered. In other words, it’s not just about whether inflammasome proteins are expressed, but also when & maybe even where they’re synthesized.

6. Even after NLRP3 priming has already occurred, ongoing protein synthesis is required for the inflammasome to assemble (pulsing LPS-primed macrophages with cycloheximide shortly before activating NLRP3 profoundly paralyzed the formation of ASC specks)! 🤯

These data deeply challenged my long-held assumptions about the functional role of “priming” in inflammasome regulation. So why do we think it matters?

5. Our data implicate the inflammasome adaptor protein ASC—long thought to be biosynthetically static—as a translationally dynamic inflammasome component whose de novo synthesis during PAMP sensing is both mTOR-driven & spatially regulated (in contrast, NLRP3’s synthesis is agnostic to mTOR).

4. mTOR-driven biosynthetic rewiring is important here. Using polysome-seq, we assessed the translation landscape shaped by BCAA-mTOR signaling, revealing substantial mRNA-specific translational sensitivity. This is where the story takes a turn—NLRP3 doesn't turn out to be the protagonist! 🧐

3. Of note, this axis is functionally important in vivo during LPS-induced endotoxemia—inflammasome responses are tuned by dietary BCAA intake! 🍔

2. Through this screen, the essential BCAAs (leucine, isoleucine & valine) popped out as major drivers of NLRP3 inflammasome function. And it’s all about timing ⏰: when macrophages sense BCAAs in their environment, they more rapidly assemble the inflammasome & execute pyroptosis.

1. The amino acid (AA) environment is a key regulator of non-redundant aspects of the macrophage inflammatory program, with IL-1 exhibiting dynamic sensitivity to stress imposed by the restriction of individual AAs. The screen we generated to show this is very powerful & we're happy to share! 🧫

I’m stoked to share my postdoc work with @sunnyshinlab.bsky.social, a collaborative effort with @metabailism.bsky.social & Brian Goldspiel, aided by many valued collaborators: Environmental Amino Acid Sensing Regulates the Rate of ASC Translation and NLRP3 Inflammasome Assembly. Some big takeaways:

The NIH has lost its scientific integrity. So we left “We can no longer lend our credibility to an organization that has lost its integrity,” write four scientists and administrators who recently resigned from the NIH.

Powerful piece in STAT this morning from some NIH staff members who have resigned

www.statnews.com/2026/01/10/n...

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A dietary pan-amino acid dropout screen in vivo reveals a critical role for histidine in T-ALL Dietary interventions show therapeutic potential in cancer, but systematic comparisons are lacking. We performed a dietary pan-amino acid dropout screen in an orthotopic model of NOTCH1-driven T-cell ...

Which amino acid is most required for T cell leukemia?
Did you guess...histidine?
excited to see this out, congrats to Komal and @herranzlab.bsky.social and coauthors!
www.biorxiv.org/content/10.6...

Frontiers | Glycolytic reprogramming of resident alveolar macrophages contributes to reduced SOCS3 secretion in non-small cell lung cancer Alveolar macrophages (AMs), the resident immune cells of the lung, play a critical role in maintaining pulmonary homeostasis, in part through the secretion o...

Happy to see the final piece of my PhD research out in the world: www.frontiersin.org/journals/imm...

Here, we provide more evidence that the homeostatic biology of alveolar macrophages is highly sensitive to glucose metabolism, this time in the context of non-small cell lung cancer. 🫁 🧫