@danapeer.bsky.social
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!
July 28, 2025 at 5:13 PM
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
July 21, 2025 at 11:54 PM
A huge congratulations to my better half, Itsik Pe'er, @iscb.bsky.social
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.
July 3, 2025 at 2:22 PM
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 ->
July 3, 2025 at 2:20 PM
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 ->
July 3, 2025 at 2:15 PM
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 ->
July 3, 2025 at 2:09 PM
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 ->
July 3, 2025 at 2:05 PM
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 ->
July 3, 2025 at 2:01 PM
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 ->
July 3, 2025 at 1:56 PM
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 ->
July 3, 2025 at 1:51 PM
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 ->
July 3, 2025 at 1:48 PM
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 ->
July 3, 2025 at 1:26 PM
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%. -->
July 3, 2025 at 1:21 PM
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%. -->
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.
May 15, 2025 at 1:52 AM
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.
9) 10X cell segmentation gets the neutrophils at the cost of losing the important tuft cells that are mixed in with the nearby TA cells, losing and confounding biology. Only segger finds optimal balance between sensitivity and specificity to capture and interpret the rich biology in these images.
March 20, 2025 at 12:06 PM
9) 10X cell segmentation gets the neutrophils at the cost of losing the important tuft cells that are mixed in with the nearby TA cells, losing and confounding biology. Only segger finds optimal balance between sensitivity and specificity to capture and interpret the rich biology in these images.
8) No parameters can save this, any threshold that captures neutrophils brings in an intolerable level of noise, removing all structure in the data (see gene-gene covariance matrix). Segger’s ability to assign transcripts based on gene identity can faithfully recover this biology.
March 20, 2025 at 12:04 PM
8) No parameters can save this, any threshold that captures neutrophils brings in an intolerable level of noise, removing all structure in the data (see gene-gene covariance matrix). Segger’s ability to assign transcripts based on gene identity can faithfully recover this biology.
7) This matters! 10X nuclear segmentation often used due to less false positives, ignores 70% of the transcripts and misses key biology. In this inflamed colon, nuclear segmentation does not capture the neutrophils nor the cell-cell communication driving the inflammation and observed expression.
March 20, 2025 at 12:00 PM
7) This matters! 10X nuclear segmentation often used due to less false positives, ignores 70% of the transcripts and misses key biology. In this inflamed colon, nuclear segmentation does not capture the neutrophils nor the cell-cell communication driving the inflammation and observed expression.
6) Segger provides a biologically faithful segmentation with much contamination quantitatively and also this contamination is more biologically preserving; among differentially expressed genes between ground truth and Segger segmentation, one does not get non-epithelial genes in epithelial cells
March 20, 2025 at 11:57 AM
6) Segger provides a biologically faithful segmentation with much contamination quantitatively and also this contamination is more biologically preserving; among differentially expressed genes between ground truth and Segger segmentation, one does not get non-epithelial genes in epithelial cells
5) Segmentation is framed as link prediction trained using graph attention on confident nuclear edges, learning to link cytoplasmic transcripts based on spatial proximity and their features. Propagation through the graph also takes into account “what other genes are assigned to this cell”.
March 20, 2025 at 11:53 AM
5) Segmentation is framed as link prediction trained using graph attention on confident nuclear edges, learning to link cytoplasmic transcripts based on spatial proximity and their features. Propagation through the graph also takes into account “what other genes are assigned to this cell”.
4) Core idea: build a heterogenous graph of both transcripts and cells. Edges between transcripts based on spatial proximity; transcript to cell edge is an assignment. Transcripts are associated with their gene, encoded via a gene embedding. Cells are associated with their geometric features.
March 20, 2025 at 11:50 AM
4) Core idea: build a heterogenous graph of both transcripts and cells. Edges between transcripts based on spatial proximity; transcript to cell edge is an assignment. Transcripts are associated with their gene, encoded via a gene embedding. Cells are associated with their geometric features.
3) Case in point, an example of 10X’s default segmentation on a lung cancer sample, based on ground truth membrane staining one can see pervasive contamination (orange) and this matters as it assigns epithelial cells immune, fibroblast and endothelial transcripts messing up all biological inference.
March 20, 2025 at 11:46 AM
3) Case in point, an example of 10X’s default segmentation on a lung cancer sample, based on ground truth membrane staining one can see pervasive contamination (orange) and this matters as it assigns epithelial cells immune, fibroblast and endothelial transcripts messing up all biological inference.
The best lab in the world and our team
March 9, 2025 at 3:49 PM
The best lab in the world and our team
9) Clones throughout the phylogeny do not appear to be constrained by their lineage and express a diversity of archetypal phenotypes. Genetically, CNA burden correlates with increased plasticity. Thus plasticity is the major hallmark of tumor cell adaptation to metastasis.
March 7, 2025 at 12:27 PM
9) Clones throughout the phylogeny do not appear to be constrained by their lineage and express a diversity of archetypal phenotypes. Genetically, CNA burden correlates with increased plasticity. Thus plasticity is the major hallmark of tumor cell adaptation to metastasis.
8) This was a case of convergent adaptation, where many distinct clones from distant parts of the phylogeny all had the ability converged on this lipid metabolism program highlighting the awesome power of tumor cell plasticity
March 7, 2025 at 12:17 PM
8) This was a case of convergent adaptation, where many distinct clones from distant parts of the phylogeny all had the ability converged on this lipid metabolism program highlighting the awesome power of tumor cell plasticity
7) The approach identified organ site specific rewiring of lipid metabolism in the peritoneum. We found this program in both peritoneum metastases from opposite flanks. This is likely an adaptation to the abundance of metabolically active adipose tissue in the understudied peritoneum.
March 7, 2025 at 12:13 PM
7) The approach identified organ site specific rewiring of lipid metabolism in the peritoneum. We found this program in both peritoneum metastases from opposite flanks. This is likely an adaptation to the abundance of metabolically active adipose tissue in the understudied peritoneum.