Shoval Miyara
@shovalmiyara.bsky.social
Studying fibrosis at the labs of Prof. Uri Alon @urialonlab.bsky.social and Prof. Eldad Tzahor @Weizmann Institute of Science.
Interestingly, when we analyzed published scRNA-seq datasets of other CIACs: esophageal and gastric adenocarcinomas, we found similar CAF archetypes and autocrine ligands, suggesting the ❄️cold fibrosis program as a shared, targetable circuit across CIACs
September 22, 2025 at 3:09 PM
Interestingly, when we analyzed published scRNA-seq datasets of other CIACs: esophageal and gastric adenocarcinomas, we found similar CAF archetypes and autocrine ligands, suggesting the ❄️cold fibrosis program as a shared, targetable circuit across CIACs
Using NicheNet and cell-cell network modeling, we mapped growth factor signaling in LUSC and found that CAFs are maintained by a self-sustaining autocrine loop (TIMP1, INHBA, TGFB1, GMFB), independent of macrophages- mirroring❄️ cold fibrosis circuits in heart & liver
September 22, 2025 at 3:09 PM
Using NicheNet and cell-cell network modeling, we mapped growth factor signaling in LUSC and found that CAFs are maintained by a self-sustaining autocrine loop (TIMP1, INHBA, TGFB1, GMFB), independent of macrophages- mirroring❄️ cold fibrosis circuits in heart & liver
Using Pareto task inference analysis, we find that CAFs in LUSC adopt a myofibroblast and stress-related states analogous to cold fibrosis after myocardial infarction
September 22, 2025 at 3:09 PM
Using Pareto task inference analysis, we find that CAFs in LUSC adopt a myofibroblast and stress-related states analogous to cold fibrosis after myocardial infarction
Interestingly, while the fibrotic stroma is ❄️cold, the adaptive immune microenvironment remains “hot,” with enriched T and B cells
September 22, 2025 at 3:09 PM
Interestingly, while the fibrotic stroma is ❄️cold, the adaptive immune microenvironment remains “hot,” with enriched T and B cells
We find that LUSC tumors show a ❄️cold fibrotic architecture: macrophages are depleted while fibroblasts are dramatically elevated
September 22, 2025 at 3:09 PM
We find that LUSC tumors show a ❄️cold fibrotic architecture: macrophages are depleted while fibroblasts are dramatically elevated
LUSC often presents with desmoplastic, ECM-rich regions and has proven largely refractory to targeted therapies
September 22, 2025 at 3:09 PM
LUSC often presents with desmoplastic, ECM-rich regions and has proven largely refractory to targeted therapies
In 🔥 hot fibrosis, macrophages and fibroblasts reciprocally support each other. In ❄️ cold fibrosis, fibroblasts go solo, sustaining themselves through an autocrine growth factor loop
September 22, 2025 at 3:09 PM
In 🔥 hot fibrosis, macrophages and fibroblasts reciprocally support each other. In ❄️ cold fibrosis, fibroblasts go solo, sustaining themselves through an autocrine growth factor loop
Our work made it to the cover of @cp-cellsystems.bsky.social ! 🥳
Cold and hot fibrosis define clinically distinct cardiac pathologies
www.cell.com/cell-systems...
Special thanks to Danielle Kimchi for creating this beautiful cover! 🎉
@urialonlab.bsky.social @eldadtzahor.bsky.social
Cold and hot fibrosis define clinically distinct cardiac pathologies
www.cell.com/cell-systems...
Special thanks to Danielle Kimchi for creating this beautiful cover! 🎉
@urialonlab.bsky.social @eldadtzahor.bsky.social
March 20, 2025 at 6:42 PM
Our work made it to the cover of @cp-cellsystems.bsky.social ! 🥳
Cold and hot fibrosis define clinically distinct cardiac pathologies
www.cell.com/cell-systems...
Special thanks to Danielle Kimchi for creating this beautiful cover! 🎉
@urialonlab.bsky.social @eldadtzahor.bsky.social
Cold and hot fibrosis define clinically distinct cardiac pathologies
www.cell.com/cell-systems...
Special thanks to Danielle Kimchi for creating this beautiful cover! 🎉
@urialonlab.bsky.social @eldadtzahor.bsky.social
This work wouldn't have been possible without the persistent support of my two amazing mentors @eldadtzahor.bsky.social & @urialonlab.bsky.social
February 19, 2025 at 3:52 PM
This work wouldn't have been possible without the persistent support of my two amazing mentors @eldadtzahor.bsky.social & @urialonlab.bsky.social
Using MAMY mice we demonstrate that inhibition of TIMP1 following myocardial infarction by neutralizing antibodies can reduce myofibroblast proliferation and subsequent fibrosis.
February 19, 2025 at 3:52 PM
Using MAMY mice we demonstrate that inhibition of TIMP1 following myocardial infarction by neutralizing antibodies can reduce myofibroblast proliferation and subsequent fibrosis.
n-vitro gain and loss of function experiments revealed that TIMP1 can act as a growth factor for cardiac myofibroblasts derived from mice and non-human-primate hearts
February 19, 2025 at 3:52 PM
n-vitro gain and loss of function experiments revealed that TIMP1 can act as a growth factor for cardiac myofibroblasts derived from mice and non-human-primate hearts
We used NicheNet analysis on scRNAseq data (doi.org/10.1016/j.ce...), generously shared by @elviraforte.bsky.social and team, to identify TIMP1 as a key post-myocardial infarction autocrine growth factor for myofibroblasts
February 19, 2025 at 3:52 PM
We used NicheNet analysis on scRNAseq data (doi.org/10.1016/j.ce...), generously shared by @elviraforte.bsky.social and team, to identify TIMP1 as a key post-myocardial infarction autocrine growth factor for myofibroblasts
We used the theoretical model to expose a vulnerability of ❄️cold fibrosis- the myofibroblast autocrine growth factor loop
February 19, 2025 at 3:52 PM
We used the theoretical model to expose a vulnerability of ❄️cold fibrosis- the myofibroblast autocrine growth factor loop
Using ParTi (nature.com/articles/nme...), we show that in❄️cold fibrosis fibroblasts acquire a persistent fibrotic archetype (state), while macrophages return to homeostatic functions
February 19, 2025 at 3:52 PM
Using ParTi (nature.com/articles/nme...), we show that in❄️cold fibrosis fibroblasts acquire a persistent fibrotic archetype (state), while macrophages return to homeostatic functions
We focused MI induced ❄️cold fibrosis and showed that it is a conserved outcome in mice, pigs, and humans
February 19, 2025 at 3:52 PM
We focused MI induced ❄️cold fibrosis and showed that it is a conserved outcome in mice, pigs, and humans
Anecdotally, we also find abundant macrophages & myofibroblasts around the LAD ligation suture in MI, resembling a foreign body response. This suggests that the local reaction to the suture aligns with 🔥hot fibrosis.
February 19, 2025 at 3:52 PM
Anecdotally, we also find abundant macrophages & myofibroblasts around the LAD ligation suture in MI, resembling a foreign body response. This suggests that the local reaction to the suture aligns with 🔥hot fibrosis.
28 days following chronic pressure overload (TAC) MAMY mice hearts showed increased macrophage-myofibroblast numbers- depending on the fibrotic degree. We conclude that chronic cardiac damage leads to 🔥hot fibrosis.
February 19, 2025 at 3:52 PM
28 days following chronic pressure overload (TAC) MAMY mice hearts showed increased macrophage-myofibroblast numbers- depending on the fibrotic degree. We conclude that chronic cardiac damage leads to 🔥hot fibrosis.
If acute MI leads to ❄️cold fibrosis? What kind of injuries would lead to hot fibrosis in the heart?
Our model suggests that chronic or repetitive injuries can lead to 🔥hot fibrosis. www.sciencedirect.com/science/arti...
Our model suggests that chronic or repetitive injuries can lead to 🔥hot fibrosis. www.sciencedirect.com/science/arti...
February 19, 2025 at 3:52 PM
If acute MI leads to ❄️cold fibrosis? What kind of injuries would lead to hot fibrosis in the heart?
Our model suggests that chronic or repetitive injuries can lead to 🔥hot fibrosis. www.sciencedirect.com/science/arti...
Our model suggests that chronic or repetitive injuries can lead to 🔥hot fibrosis. www.sciencedirect.com/science/arti...
Using the MAMY mice, we find that acute myocardial infarction (MI) results in❄️cold fibrosis- a myofibroblast-dominated state, with low macrophage contribution
February 19, 2025 at 3:52 PM
Using the MAMY mice, we find that acute myocardial infarction (MI) results in❄️cold fibrosis- a myofibroblast-dominated state, with low macrophage contribution
To do that we developed a macrophage-myofibroblast double reporter mouse line, named ‘MAMY’ (Sweetheart in Hebrew slang), based on the myofibroblast lineage reporter (Postn-MCM) (Kanisicak, et al. 2016), and the monocyte-macrophage reporter Cx3cr1-GFP (Jung, et al. 2003)
February 19, 2025 at 3:52 PM
To do that we developed a macrophage-myofibroblast double reporter mouse line, named ‘MAMY’ (Sweetheart in Hebrew slang), based on the myofibroblast lineage reporter (Postn-MCM) (Kanisicak, et al. 2016), and the monocyte-macrophage reporter Cx3cr1-GFP (Jung, et al. 2003)
Miri Adler & @urialonlab.bsky.social
developed a theoretical model based on a macrophage-myofibroblast circuit to predict injury outcomes. It predicts two fibrosis types: hot🔥fibrosis, where both cell types support each other, and myofibroblast-driven cold❄️fibrosis.
developed a theoretical model based on a macrophage-myofibroblast circuit to predict injury outcomes. It predicts two fibrosis types: hot🔥fibrosis, where both cell types support each other, and myofibroblast-driven cold❄️fibrosis.
February 19, 2025 at 3:52 PM
Miri Adler & @urialonlab.bsky.social
developed a theoretical model based on a macrophage-myofibroblast circuit to predict injury outcomes. It predicts two fibrosis types: hot🔥fibrosis, where both cell types support each other, and myofibroblast-driven cold❄️fibrosis.
developed a theoretical model based on a macrophage-myofibroblast circuit to predict injury outcomes. It predicts two fibrosis types: hot🔥fibrosis, where both cell types support each other, and myofibroblast-driven cold❄️fibrosis.
Fibrosis is defined by excessive #ECM deposition. It’s an incredibly complex process involving numerous interactions between different cell types and molecules. In the heart, there is still no effective treatment for fibrosis- posing a major challenge to the field🫀
February 19, 2025 at 3:52 PM
Fibrosis is defined by excessive #ECM deposition. It’s an incredibly complex process involving numerous interactions between different cell types and molecules. In the heart, there is still no effective treatment for fibrosis- posing a major challenge to the field🫀