Excited to share our paper on deciphering the design & control principles of tissue scaling w/ Luisa Arispe! Amazing work by co-first authors Danielle Pi and Jonas Braun. We show *differentiated* endothelial cell proliferate in waves with ultrafast cell cycle time of ~5h
www.cell.com/cell-systems...

This is brilliant!

Again I would like to thank the Pezcoller Foundation for inviting me to the 36th Pezcoller Symposium in beautiful Trento. They were warm, pampering and wonderful hosts and science was top notch and delightful. I had fabulous time!

A huge congratulations to my better half, Itsik Pe'er, @iscb.bsky.social

This is a great tool!

YouTube video by Universität Zürich Bioimaging | UZH Research Spotlight

And just like that @katharinaweins.bsky.social and Elvira Isenring managed to make us look cooler than we'll ever be:
www.youtube.com/watch?v=8t8R...

The line up for this conference is amazing and I am really looking forward to all the talks and discussions tomorrow!

Deadline in 9 days - apply now!

My First Substantial Independent Research Award Was Terminated Early. Can My ESI Status Be Reinstated? June 12, 2025 Investigators lose their Early Stage Investigator (ESI) eligibility when they successfully compete for and receive a substantial independent research award. In the event an investigator’s first substantial independent research award is terminated within the first three years of the project period, and this was not due to scientific misconduct or other disqualifying events, the investigator can request the reinstatement of ESI status, using the ESI Extensions request tool in eRA commons. See Requesting an Extension for instructions. For more, see the Early Stage Investigators FAQ page.

For ESIs dealing with grants being rescinded: if an investigator’s 1st substantial independent research award is terminated within the first 3 years of the project period (not due to scientific misconduct ) they can request the reinstatement of ESI status

grants.nih.gov/news-events/...

12) In summary P53 is a guardian of plasticity. Its loss loss promotes malignant progression by enabling epithelial plasticity and immune evasion. p53 activation or KRAS inhibition removes progenitor cells and dismantles their tumor-like niche.

11) Loss of p53 allows for the stabilization and progression of the malignant niche, allowing the progenitor cells. to persist and progress to more mesenchymal states and for their accompanying niche to stabilize and expand in size ->

10) The progenitor state and its niche are dependent on KRAS signaling. Inhibition of KRAS via drug blunts the progenitor state and dismantles their surrounding tumor like niche ->

9) Thus the progenitor states orchestrates tissue remodeling of self reinforcing tumor like niches through robust feedback loops among cell compartments ->

8) Bi-directional cell-cell communication changes along this axis, enable new modes of communication between all cell compartments in the niche ->

7) This tissue remodeling trajectory culminates in progenitor cells residing with niches abundant in activated fibroblasts and immunosuppressive myeloid cells reminiscent of advanced PDAC ->

6) We found coordinated changes in gene expression across multiple cell type compartments along this axis, including changes in expression of cell-cell communication genes. Just defining a pseudo-time of niche remodeling from a single spatial snapshot ->

5) To track this remodeling we anchored spatial neighborhoods (niches) around epithelial cells, placed these niches the gastric to progenitor axis based on their mean epithelial state and characterized how all other TME states change along this axis ->

4) The gastric to progenitor axis is the strongest axis of variation among epithelial pre-malignant cells. Thus we collected Xenium data to understand the tissue remodeling that occurs along this axis ->

3) These progenitor cells accumulate in disorganized lesions upon inflammation and are reminiscent of highly plastic cells found in normal regeneration. Thus we find an additional role for P53 as putting the breaks on plasticity and keeping it in check ->

2) We find that P53 is uniquely activated in the highly plastic progenitor state. This highly plastic state activates KRAS + other oncogenic signals, P53 + other tumor suppressors. This state expands under inflammation, from 1% to 30%. -->

Oncogenic and tumor-suppressive forces converge on a progenitor-orchestrated niche to shape early tumorigenesis The transition from benign to malignant growth is a pivotal yet poorly understood step in cancer progression that marks the shift from a pathologically inert condition to a clinically lethal disease. ...

I am thrilled to share with the world a new preprint, spearheaded by the truly amazing Jose Reyes in partnership with the Lowe lab. The paper sheds light on benign to malignant transition in PDAC, uncovering roles of plasticity, tissue remodeling and P53. -> www.biorxiv.org/content/10.1...

I am so honored to be an awardee from a foundation that recognizes and funds innovation. I wish more foundations shared the Mark foundations vision. Also, the Pezcoller meeting was so fantastic this year, we were hardly the only highlights.

Damage and Misrepair Signatures: Compact Representations of Pan-cancer Mutational Processes Mutational signatures of single-base substitutions (SBSs) characterize somatic mutation processes which contribute to cancer development and progression. However, current mutational signatures do not ...

Please check out our new approach to modeling somatic mutation signatures.

DAMUTA has independent Damage and Misrepair signatures whose activities are more interpretable and more predictive of DNA repair defects, than COSMIC SBS signatures 🧬🖥️🧪

www.biorxiv.org/content/10.1...

The Single-cell Analytics Innovation Lab
@mskcancercenter.bsky.social is expanding and looking for ML-oriented computational biologists. Join our team based in NYC to work on cutting-edge single-cell & spatial transcriptomics methods in collaboration with leading research labs. bit.ly/4lTEr2t

YouTube video by Amanpour and Company Breakthrough Prize-Winning Biochemist on the Deadly Cost of Funding Cuts | Amanpour and Company

David Liu @harvard.edu beautifully articulates the criticality of basic science funding for developing revolutionary therapeutics like life-saving base editors 👏

youtu.be/8YhJM6zxYDw?...

🧠 Excited to share my main PhD project! We mapped the regulatory rules governing Glioblastoma plasticity using single-cell multi-omics and deep learning. This work is part of a two-paper series with @bayraktarlab.bsky.social @oliverstegle.bsky.social and @moritzmall.bsky.social, Preprint at end🧵👇

🚨 Impressive PhD work by Manu!

Our new method scDORI decodes plasticity regulators at single-cell multi-omic resolution — scaling to millions of cells and uncovering the regulatory logic driving glioblastoma heterogeneity.

🔍 Dive into the thread below and the preprint for all the insights!

How does tumour heterogeneity arise? How can we predict cancer cell plasticity? In 2 new studies, we trace #glioblastoma heterogeneity to a spatial cancer cell trajectory w. multimodal cell atlassing bit.ly/4mkrWgs & predict plasticity w. snRNA/ATAC+deep learning bit.ly/3FbI6Ic 🧵

5) To further clarify the full cell circuit see the image below: T cells produce IFNγ, supporting maturation of conventional DC2 cells into migratory CCR7+ DCs. These DCs produce IL-12 and IL-15 to support the survival and proliferation of NK cells, which control the expansion of metastatic cells.

4) Rigorous and basic science that elucidates how tumor immunology works in the leptomeningeal space can lead to better therapies for this lethal and debilitating metastatic site. Basic science matters!