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@idoamitlab.bsky.social

150 followers 49 following 26 posts

Single Cell Gescheft @WeizmannScience http://www.weizmann.ac.il/immunology/AmitLab/front

www.weizmann.ac.il

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idoamitlab.bsky.social @idoamitlab.bsky.social · Apr 10

We are excited to share our new study @cp-cancercell.bsky.social identifying Zeb2 as a master genetic switch controlling the tumor-associated macrophage (TAM) program. Led by Fadi Sheban, Truong San Phan, Kai Kun Xie & @florianingelfinger.bsky.social. (1/20)
www.cell.com/cancer-cell/...

ZEB2 is a master switch controlling the tumor-associated macrophage program

Sheban et al. present a single-cell CRISPR screen to dissect macrophage gene regulation in a pan-cancer tumor-associated macrophage (TAM) atlas. Using a generative model, they identify ZEB2 as a key d...

www.cell.com

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Reposted

EACR - European Association for Cancer Research @helloeacr.bsky.social · May 21

Did you catch our latest podcast episode?

Our guests in episode 22 of The Cancer Researcher Podcast explore the evolution of the cancer field and why optimism is more important than ever in science:

Curiosity, optimism and collaboration: research insights from three award winning scientists - Episode 22 of The Cancer Researcher Podcast - The Cancer Researcher

Karin de Visser, Ido Amit and Marta Kovatcheva talk about their research, career journeys, and excitement for the future of cancer research.

magazine.eacr.org

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Reposted

Oliver Harschnitz @harschnitz.bsky.social · May 20

It was a pleasure to chair today's session featuring @idoamitlab.bsky.social, Silvia Beatini, Sally Cowley, @mfwells.bsky.social, and Andrea Ditadi. A stunning overview of single cell biology, immunotherapy, piRNAs, and microglia biology. #neurogen25

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EACR - European Association for Cancer Research @helloeacr.bsky.social · May 14

🚨 New podcast episode!

In this insightful and honest conversation, award winners Karin de Visser, Ido Amit and @martakova.bsky.social talk about their research, career journeys, and excitement for the future of cancer research:

magazine.eacr.org/curiosity-op...

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idoamitlab.bsky.social @idoamitlab.bsky.social · Apr 25

Registration for #SCG2025 in the beautiful Stockholm Archipelago will open on Monday, April 28 at 15.00 CEST. Space is limited so don’t miss your registration!: registration.invajo.com/82ec3735-7cb...
Conference web page: conferences.weizmann.ac.il/SCG2025/

Reposted

RTN Conference @rtnconference.bsky.social · Apr 23

#ReThinkNeuroimmunology
3 day think tank exploring the biggest discoveries & breakthroughs in neuroimmunology.
Organized by @quintanalabhms.bsky.social @bethstevenslab.bsky.social @jonykipnis.bsky.social @idoamitlab.bsky.social #RejaneRua
Registrations 🔗 genelayinstitute.org/rtn/

RTN Conference @rtnconference.bsky.social · Apr 17

[email protected] @weizmanninstitute.bsky.social @genelayinstitute.bsky.social @massgenbrigham.bsky.social

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Alejo Rodriguez-Fraticelli @alejofraticelli.bsky.social · Apr 16

EMBO workshop on Single Cell Lineage Tracing!

Sept 18-21, 2025 in Girona, Spain.

Registration is OPEN!!!!!

Tons of opportunities for talks are available (incl. full length ones).

meetings.embo.org/event/25-lineage-tracing

@perielab.bsky.social
@idoamitlab.bsky.social

#EMBOlineagetracing

Lineage tracing: Dynamics, cellular memory, and somatic evolution

Recent advances in high-resolution lineage tracing technologies and single-cell genomics are allowing researchers to quantify cell state dynamics at unprecedented scales. Across cancer and immunity, …

meetings.embo.org

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RTN Conference @rtnconference.bsky.social · Apr 16

🚨Registrations now live!
Check out this amazing line up of speakers at #RTN #ReThinkNeuroimmunology organised by @quintanalabhms.bsky.social @bethstevenslab.bsky.social @jonykipnis.bsky.social @idoamitlab.bsky.social #RejaneRua
Register here: genelayinstitute.org/rtn/

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idoamitlab.bsky.social @idoamitlab.bsky.social · Apr 16

See you in Boston in October!
@idoamitlab.bsky.social , @jonykipnis.bsky.social , @quintanalab.bsky.social, @bethstevenslab.bsky.social

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idoamitlab.bsky.social @idoamitlab.bsky.social · Apr 16

#ReThinkNeuroimmunology is back!
Excited about new frontiers and technologies in NeuroImmunology? Here is the one conference you don't want to miss.
Registration is open and space is limited - genelayinstitute.org/rtn/

ReThink - The Gene Lay Institute

genelayinstitute.org

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idoamitlab.bsky.social @idoamitlab.bsky.social · Apr 12

Thank you Carlos! 🙏🏻

idoamitlab.bsky.social @idoamitlab.bsky.social · Apr 10

Finally, huge thanks to our collaborators @yuvalshap.bsky.social, @dahanlab.bsky.social, all of our co-authors, and the @cp-cancercell.bsky.social editorial team and reviewers for their constructive feedback! (20/20)

idoamitlab.bsky.social @idoamitlab.bsky.social · Apr 10

In summary, our research established the blueprint of tumor macrophages and defined Zeb2 as a master switch controlling the TAM program, with implications for clinical translation and TAM-targeted immunotherapy. (19/20)

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idoamitlab.bsky.social @idoamitlab.bsky.social · Apr 10

Among the tumor models we tested, we used an orthotopic bladder cancer model and found that intravesical treatment with CpG-conjugated Zeb2 siRNA showed robust tumor control, with the potential to replace conventional BCG therapy. (18/20)

idoamitlab.bsky.social @idoamitlab.bsky.social · Apr 10

By design, CpG alone activates inflammatory pathways in TAMs - but adding Zeb2 silencing improved significantly TAM reprogramming and tumor control across different tumor models. (17/20)

idoamitlab.bsky.social @idoamitlab.bsky.social · Apr 10

To evaluate the in vivo impact of targeting Zeb2, and since TFs are not easily targeted - we teamed up with the Kortylewski lab to design a CpG-conjugated Zeb2 siRNA that delivers Zeb2 siRNA preferably to TAMs through their expression of the CpG receptor TLR9. (16/20)

idoamitlab.bsky.social @idoamitlab.bsky.social · Apr 10

Next, since Zeb2 is a transcription factor, we asked if it also controls these programs at the chromatin level. ATAC-seq revealed that Zeb2 KO causes massive enhancer remodeling—opening sites near anti-tumor genes while closing pro-tumor ones. (15/20)

idoamitlab.bsky.social @idoamitlab.bsky.social · Apr 10

Functionally, Zeb2 KO macrophages were less immunosuppressive and robustly upregulated immune activities such as antigen presentation—especially to CD4+ T cells, activating more IFN-γ–producing T cells in multiple functional in-vitro models. (14/20)

idoamitlab.bsky.social @idoamitlab.bsky.social · Apr 10

To validate our proposed anti-tumor score in a human context, we compared it to the CXCL9:SPP1 TAM polarity score linked to patient survival (beautiful work by Bill et al.). The effect of each regulator on the activity scores correlated well, with Zeb2 topping the list. (13/20)

idoamitlab.bsky.social @idoamitlab.bsky.social · Apr 10

With this, we established a TAM functional network and proposed a quantitative reprogramming metric—an 'anti-tumor score': how much a perturbation upregulates anti-tumor and downregulates pro-tumor functions. Among known hits like Trem2, Zeb2 emerged as a key switch. (12/20)

idoamitlab.bsky.social @idoamitlab.bsky.social · Apr 10

Next, we went back to our network and asked how the different perturbations affect these TAM programs. This is useful. Why? Because a major reprogramming target would upregulate anti-tumor (e.g. IFN-response) and downregulate pro-tumor (e.g. immunosuppression) programs. (11/20)

idoamitlab.bsky.social @idoamitlab.bsky.social · Apr 10

To understand how the different perturbations reprogrammed TAMs, we grouped autocorrelated genes using MrVI’s perturbation-aware latent space. This yielded distinct gene modules with known roles in TAM biology, linked to either positive or negative tumor immunity. (10/20)

idoamitlab.bsky.social @idoamitlab.bsky.social · Apr 10

This AI-driven analysis enabled us to construct a perturbation network, where perturbations that evoke similar effects on the single-cell states are located in close proximity—and vice versa. (9/20)

idoamitlab.bsky.social @idoamitlab.bsky.social · Apr 10

To systematically resolve how candidate regulators impact macrophage functions we collaborated with the Yosef lab who recently developed MrVI, a deep generative model designed to dissect how sample-level covariates like gene perturbation affect gene expression in single cells. (8/20)

idoamitlab.bsky.social @idoamitlab.bsky.social · Apr 10

The first look at the data confirmed that the putative regulators were effectively targeted—the blue diagonal indicates reduced gene expression of the perturbed genes. But the data, as you can see, is complex, high-dimensional, and not easily interpretable. (7/20).