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.
And a special thank you to the amazing Shachaf Frenkel, Avi Mayo, and Itay Ben Shalom from
@urialonlab.bsky.social lab!!!
@urialonlab.bsky.social lab!!!
September 22, 2025 at 3:09 PM
And a special thank you to the amazing Shachaf Frenkel, Avi Mayo, and Itay Ben Shalom from
@urialonlab.bsky.social lab!!!
@urialonlab.bsky.social lab!!!
Extended thanks to Eviatar Weizman, Yaniv Stein, Kfir Baruch Umansky, @jacobelk.bsky.social, @shimritmayer.bsky.social and Miri Adler @hebrewuniversity.bsky.social 🙏
September 22, 2025 at 3:09 PM
Extended thanks to Eviatar Weizman, Yaniv Stein, Kfir Baruch Umansky, @jacobelk.bsky.social, @shimritmayer.bsky.social and Miri Adler @hebrewuniversity.bsky.social 🙏
Thank you to our amazing collaborators at McGill University including the amazing team of Prof. Lorenzo Ferri, Veena Sangwan, Nicholas Bertos, Julie Berube, Sophie Camilleri-Broet, Spyridon Oikonomopoulos, Haig Djambazian, Pierre-Olivier Fiset, and Jiannis Ragoussis🇨🇦🦾🦾🦾
September 22, 2025 at 3:09 PM
Thank you to our amazing collaborators at McGill University including the amazing team of Prof. Lorenzo Ferri, Veena Sangwan, Nicholas Bertos, Julie Berube, Sophie Camilleri-Broet, Spyridon Oikonomopoulos, Haig Djambazian, Pierre-Olivier Fiset, and Jiannis Ragoussis🇨🇦🦾🦾🦾
hank you to our worldwide collaborators, including Philippe Gascard, Deng Pan, and Joseph A. Caruso from Thea Tlsty's lab, and to Michael Strasser & David Gibbs from Prof. Sui Huang's lab at the Institute for Systems Biology (ISB)🇺🇸
September 22, 2025 at 3:09 PM
hank you to our worldwide collaborators, including Philippe Gascard, Deng Pan, and Joseph A. Caruso from Thea Tlsty's lab, and to Michael Strasser & David Gibbs from Prof. Sui Huang's lab at the Institute for Systems Biology (ISB)🇺🇸
Huge thanks to the LUSC patients who generously contributed samples, who made this project possible🫁
September 22, 2025 at 3:09 PM
Huge thanks to the LUSC patients who generously contributed samples, who made this project possible🫁
This work would not have been possible without the incredible mentorship of @urialonlab.bsky.social @eldadtzahor.bsky.social, @shouval.bsky.social & Prof. Thea Tlsty (@ucsanfrancisco.bsky.social)
September 22, 2025 at 3:09 PM
This work would not have been possible without the incredible mentorship of @urialonlab.bsky.social @eldadtzahor.bsky.social, @shouval.bsky.social & Prof. Thea Tlsty (@ucsanfrancisco.bsky.social)
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
This is especially interesting as the recent TRACERx spatial proteomics analysis of LUSC showed that in LUSC, T cells and aSMA+ fibroblasts participate in a spatial relationship of mutual avoidance
aacrjournals.org/cancerdiscov...
aacrjournals.org/cancerdiscov...
Spatial Architecture of Myeloid and T Cells Orchestrates Immune Evasion and Clinical Outcome in Lung Cancer
Distinct microenvironment architectures and spatial cellular niches were observed in earlystage non–small cell lung cancer and were linked to tumor immunogenicity, metabolism, and clonal evolution, im...
aacrjournals.org
September 22, 2025 at 3:09 PM
This is especially interesting as the recent TRACERx spatial proteomics analysis of LUSC showed that in LUSC, T cells and aSMA+ fibroblasts participate in a spatial relationship of mutual avoidance
aacrjournals.org/cancerdiscov...
aacrjournals.org/cancerdiscov...
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
We teamed up with 'STORMing Cancer' (CRUK grand challenges) and profiled 197,232 cells from 16 treatment-naive LUSC patients, using single-cell RNA-seq of matched tumor & normal tissues
www.cancergrandchallenges.org/storming-can...
www.cancergrandchallenges.org/storming-can...
STORMing Cancer
Meet STORMing Cancer, whose challenge was to determine the mechanisms that cause cancer without known mutagenesis, such as obesity, in order to devise novel interventions.
www.cancergrandchallenges.org
September 22, 2025 at 3:09 PM
We teamed up with 'STORMing Cancer' (CRUK grand challenges) and profiled 197,232 cells from 16 treatment-naive LUSC patients, using single-cell RNA-seq of matched tumor & normal tissues
www.cancergrandchallenges.org/storming-can...
www.cancergrandchallenges.org/storming-can...
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
We address this question in human lung squamous cell carcinoma (LUSC), a prototypical CIAC with limited therapeutic options and poor outcomes
a man wearing a fur coat is smoking a cigarette in a black and white photo .
ALT: a man wearing a fur coat is smoking a cigarette in a black and white photo .
media.tenor.com
September 22, 2025 at 3:09 PM
We address this question in human lung squamous cell carcinoma (LUSC), a prototypical CIAC with limited therapeutic options and poor outcomes
But whether this cell circuit model extends to CIACs has remained an open question
a man wearing sunglasses is sitting in a chair making a funny face .
ALT: a man wearing sunglasses is sitting in a chair making a funny face .
media.tenor.com
September 22, 2025 at 3:09 PM
But whether this cell circuit model extends to CIACs has remained an open question
And most recently in Crohn’s disease
academic.oup.com/ecco-jcc/art...
academic.oup.com/ecco-jcc/art...
Validate User
academic.oup.com
September 22, 2025 at 3:09 PM
And most recently in Crohn’s disease
academic.oup.com/ecco-jcc/art...
academic.oup.com/ecco-jcc/art...
It was further validated in the context of kidney fibrosis
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Understanding fibrosis pathogenesis via modeling macrophage-fibroblast interplay in immune-metabolic context - Nature Communications
Renal fibrosis is a progressive process with complex etiopathology, causing organ failure. Here authors present a mathematical model, based on an in vitro system faithfully contemplating macrophage-fi...
www.nature.com
September 22, 2025 at 3:09 PM
It was further validated in the context of kidney fibrosis
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Recently, we validated this model in the context of acute (myocardial infarction) and chronic (heart failure) cardiac injuries
www.cell.com/cell-systems...
www.cell.com/cell-systems...
Cold and hot fibrosis define clinically distinct cardiac pathologies
Miyara et al. identify two types of fibrosis in cardiac pathologies: “hot fibrosis,”
involving macrophage-myofibroblast interactions in chronic injuries, and acute-injury-driven
“cold fibrosis,” contr...
www.cell.com
September 22, 2025 at 3:09 PM
Recently, we validated this model in the context of acute (myocardial infarction) and chronic (heart failure) cardiac injuries
www.cell.com/cell-systems...
www.cell.com/cell-systems...
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
The theoretical model predicts 2 fibrotic states:
❄️ cold and 🔥 hot fibrosis
❄️ cold and 🔥 hot fibrosis
September 22, 2025 at 3:09 PM
The theoretical model predicts 2 fibrotic states:
❄️ cold and 🔥 hot fibrosis
❄️ cold and 🔥 hot fibrosis
Previously, Miri Adler and @urialonlab.bsky.social introduced a basic cell circuit capable of predicting whether a tissue injury will result in healing or fibrosis
www.sciencedirect.com/science/arti...
www.sciencedirect.com/science/arti...
Principles of Cell Circuits for Tissue Repair and Fibrosis
Tissue repair is a protective response after injury, but repetitive or prolonged injury can lead to fibrosis, a pathological state of excessive scarri…
www.sciencedirect.com
September 22, 2025 at 3:09 PM
Previously, Miri Adler and @urialonlab.bsky.social introduced a basic cell circuit capable of predicting whether a tissue injury will result in healing or fibrosis
www.sciencedirect.com/science/arti...
www.sciencedirect.com/science/arti...
Chronic inflammation-associated cancers (CIACs) are deadly and difficult to treat. They often develop desmoplastic, fibrotic regions, but the principles that organize this fibrotic stroma are still unknown.
September 22, 2025 at 3:09 PM
Chronic inflammation-associated cancers (CIACs) are deadly and difficult to treat. They often develop desmoplastic, fibrotic regions, but the principles that organize this fibrotic stroma are still unknown.