Jesse Garcia Castillo, PhD

Pre-division TCF1 drop determines long-term CD8 T cell fates @biorxivpreprint.bsky.social
www.biorxiv.org/content/10.1...

#goals

Site-specific genome engineering of primary human natural killer cells for programmable anti-tumor function https://www.biorxiv.org/content/10.1101/2025.10.05.680386v1

📣do not miss out on 7&8 October: Spatial Biology in cancer and immunology research. Register NOW: events.bizzabo.com/SpatialBiology @yefis-immunology.bsky.social @efis-immunology.bsky.social

The impact has been enormous, with Tregs going from being a niche frowned-upon subset of immunology, to underpinning our entire understanding of how the immune system works. Therapies based on boosting Tregs (e.g. IL2) or bypassing Tregs (anti-CTLA4) are in the clinic.

Great to see Tregs win a Nobel prize!!

B and T cells—the organizing principle of the adaptive immune system - Lasker Foundation For their discovery of the two distinct classes of lymphocytes, B and T cells – a monumental achievement that provided the organizing principle of the adaptive immune system and launched the course of...

Renewing my yearly bet on Cooper/Miller for the Nobels.

One might think that I would learn after being wrong so many times, but one would be mistaken.

laskerfoundation.org/winners/b-an...

Foreign epitope–specific naïve Treg cells fine-tune the primary response of Tconv cells specific for the same epitope by curbing the Th1 fate while allowing a robust response @jimmunol.bsky.social @uminnpress.bsky.social
academic.oup.com/jimmunol/adv...

Eomes controls the acquisition of regulatory and cytotoxic function in CD4+ T cells that are critical for limiting immune toxicity, while maintaining persistence and tumor control after immunotherapy @cp-immunity.bsky.social
www.cell.com/immunity/ful... @fredhutch.org

Congrats!! 😀

Distinct T cell functions enable efficient immunoediting and prevent tumor emergence of developing sarcomas Cheung et al. describe efficient T cell control of nascent neoantigen+ and nearby neoantigen-negative sarcoma cells, underlying a ∼50% reduction in tumor penetrance. This otherwise imperceptible immun...

Happy to announce the publication using advanced models to understand how T cells mediate efficient immunoediting in early sarcomas.

This was a collaboration between Julie Cheung and Brian Hunt
in the lab

Thanks to Cancer Cell for publishing our work.

www.cell.com/cancer-cell/...

Best practices and tools in R and Python for statistical processing and visualization of lipidomics and metabolomics data www.nature.com/articles/s4...

Cartoon of a speculative heterogenous cell population performing mesenchymal collective cell migration.

1/12 A very special moment for me! 🎉

My first paper as corresponding author—a @jcb.org Perspective on how contact-based decision-making in collective cell migration can itself encode blueprints for complex patterns and shapes.

rupress.org/jcb/article/...

#cellbio #devbio #science

🧵for details

👀 saved

Super excited to get this out. This collab started a few years ago and is the first paper from it. Here, with experimental and computational approaches we:

1. establish that cell villages can be just as accurate (one might argue more accurate!) than arrayed-based designs

bsky.app/profile/bior...

According to news reports, NIH is on track to award nearly all of its FY25 budget. Program officers—working long hours despite staff losses—made it possible. Take a moment to thank your PO for their dedication.

A distinct population of CD8+ T cells expressing CD39 and CD73 accumulates with age and supports cancer progression - Nature Aging Bodogai et al. identify a unique subset of CD8+ T cells expressing CD39 and CD73 that accumulate during aging and are recruited to and actively promote tumor progression by suppressing antitumor CD4+ T cells. Targeting their function or recruitment attenuates tumor growth in aged mice.

A distinct population of CD8+ T cells expressing CD39 and CD73 accumulates with age and supports cancer progression @nataging.nature.com
www.nature.com/articles/s43...

Optimization of the Blocking and Signal Preservation Protocol in High‐Parameter Flow Cytometry High quality input data is the key to successful interpretation of any scientific assay. In flow cytometry, fluorescently-conjugated antibodies allow us to simultaneously measure an incredible range ...

New #flowcytometery protocol drop from Oliver Burton.

This one is on optimising blocking while preserving signal, in particular how to overcome Fc interactions and dye-dye interactions, and preventing tandem break-down.

currentprotocols.onlinelibrary.wiley.com/doi/10.1002/...

Engineered bacteria launch and control an oncolytic virus Nature Biomedical Engineering - CAPPSID relies on an engineered S. typhimurium to act as a synthetic ‘capsid’ to transcribe and deliver viral RNA inside cancer cells, launching a virus...

Very cool paper that I presented to journal club today by Singer et al, by Tal Danino and Charlie Rice labs.

I LOVE this paper!
rdcu.be/eH4le

As a postdoc in Andino lab 20 years ago, we took a similar strategy to deliver recombinant RNA viruses or saRNA by intracellular S. typhimurium.

Genetic and epigenetic screens in primary human T cells link candidate causal autoimmune variants to T cell networks - Nature Genetics Massively parallel reporter assay in primary human CD4+ T cells and bulk and single-cell CRISPR-interference screens identify candidate causal variants linked to autoimmune disease risk that modulate ...

Excited to finally present the lab's latest work in defining candidate causal genetic variants that drive autoimmune diseases and their effects on primary human T cell expression and function! www.nature.com/articles/s41...

For our #flowcytometry peeps, would you like to have a single fix/perm protocol that is optimised for everything? One that preserves fluorophores while allowing simultaneous TF and cytokine staining? How about 100-fold cheaper?

You got it:
currentprotocols.onlinelibrary.wiley.com/doi/10.1002/...

Myeloid progenitor dysregulation fuels immunosuppressive macrophages in tumours - Nature An understanding of the molecular mechanisms promoting the generation of immunoregulatory and tumour-promoting monocytes and macrophages is key to breaking the cycle of tumour myelopoiesis and develop...

📝NEW STUDY📝 Cancer's first punch when battling the immune system may be rewiring myeloid progenitors in bone marrow so they become suppressive tumor macrophages blunting T-cell attacks. Find out how in @nature.com from @samhegde.bsky.social & @miriammerad.bsky.social 🧐 www.nature.com/articles/s41...

TFH cell programs by pathogen and species - Nature Immunology CD4+ T follicular helper (TFH) cells that develop in response to a range of pathogens share aspects of a common gene signature. However, cytokine environments, rather than pathogen class, shape divers...

Preview @natimmunol.nature.com
TFH cell programs by pathogen and species
www.nature.com/articles/s41...
www.nature.com/articles/s41...

Integrin CD103 expression in naive CD8+ T cells promotes cytokine-driven acquisition of memory phenotype and effector function Integrin CD103 mediates memory T cell tissue residency by binding E-cadherin-expressing epithelial cells, but why CD103 is also expressed on circulating naive CD8+ T cells has been unclear. Li et al. report that CD103 facilitates the interaction of naive CD8+ T cells with E-cadherin-expressing dendritic cells that in turn provide cytokine-mediated cues to promote their differentiation into memory-phenotype effector T cells.

Online now: Integrin CD103 expression in naive CD8+ T cells promotes cytokine-driven acquisition of memory phenotype and effector function

an we understand biology from "infinite" amounts of perturbation data ?

- Only if we measure the relevant molecules.

Perturbations and data scale 𝐜𝐚𝐧𝐧𝐨𝐭 compensate for missing the relevant molecules.

🧵

T cells are the best. 💯

Single-cell multiomics identifies Tcf1 and Lef1 as key initiators of early thymic progenitor fate Tcf1 and Lef1 prime prethymic progenitors for Notch responsiveness, promoting early thymic progenitor fate and lineage stability.

Tcf1 and Lef1 prime prethymic progenitors for Notch responsiveness, promoting early thymic progenitor fate and lineage stability @sciimmunology.bsky.social
www.science.org/doi/10.1126/...

Dynamic regulation of the oxidative stress response by the E3 ligase TRIP12 Centered on the transcription factor NRF2 and its E3 ligase CUL3KEAP1, the oxidative stress response protects cells from damage by reactive oxygen spe…

Excited that our study identifying TRIP12 - an essential E3 ligase mutated in a neurodevelopmental disease - as a critical component of the oxidative stress response is now online. Congratulations to Andrew, Devlon and Jenny! @ucberkeleyofficial.bsky.social

www.sciencedirect.com/science/arti...

Preprint @cellpress.bsky.social: Heterogeneity and Plasticity of the Naïve CD4+ T Cell Compartment
papers.ssrn.com/sol3/papers....

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