This is a paper I am super proud of, long in the making, packed with important concepts. It was old data and n=1 (most stronge claims backed with patients), metastatic clones are endowed with plasticity to adapt to multiple organ environments.
Transcriptomic Plasticity is a Hallmark of Metastatic Pancreatic Cancer, by Christine Iacobuzio-Donahue, @danapeer.bsky.social et al.
pubmed.ncbi.nlm.nih.gov/41379552/
introduces a new single-cell method named PICASSO: Phylogenetic Inference of CNA in Single-cell RNA [...]
github.com/dpeerlab/pic...
Celebrating Christina Curtis and her well-deserved Paul Marks Prize! Some tumors are born bad. Christina uses math to find them early, predict their paths, and outsmart them. A win for cancer biology and for MSK to cheer.
My lab shows up every day to take on the rare cancers. Now we’re getting on the bikes together for Cycle for Survival. Every gift is matched (yes, doubled!), and 100% goes to rare cancer research at MSK—where rare cancers are our daily reality and the science moves the needle. bit.ly/3Y1m4xx
Meet the keynote speakers for the 2025 scverse conference!
John Marioni, Head of Computation at Genentech Research and Early Development and former head of EBI
🧵
#scverse #scverse2025 #AI #DrugDevelopment #MachineLearning #ComputationalBiology #Biotech #Pharma #Genentech
@jengreitz.bsky.social l & my lab want to co-hire a computational biologist/biostatistician with project management expertise to help map the regulatory code of the human genome and discover genetic mechanisms of disease.
Details below
careersearch.stanford.edu/jobs/computa...
Plz RT
We had many hundreds of applications for that position... Sorry
thank you!
A great read for anyone interested in perturbations and cell-fate decisions. Top notch work.
New paper from @elhamazizi.bsky.social, @bleilab.bsky.social & @danapeer.bsky.social labs: Decipher, a deep generative model to track disease trajectories in single-cell data.
📖 Read: bit.ly/4mufVnZ @columbiaseas.bsky.social @columbiacancer.bsky.social @mskcancercenter.bsky.social
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!
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%. -->
