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shovalmiyara.bsky.social
Shoval Miyara
@shovalmiyara.bsky.social
64 followers 140 following 55 posts
Studying fibrosis at the labs of Prof. Uri Alon @urialonlab.bsky.social and Prof. Eldad Tzahor @Weizmann Institute of Science.
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
🚨It’s here! Our new preprint is live on bioRxiv🚨
A fibroblast-centric network drives ❄️cold fibrosis in the tumor microenvironment of lung squamous cell carcinoma 🧵
www.biorxiv.org/content/10.1...
A fibroblast-centric network drives cold fibrosis in the tumor microenvironment of lung squamous cell carcinoma
The tumor microenvironment (TME) of chronic inflammation-associated cancers (CIACs) is shaped by cycles of injury and maladaptive repair, yet the principles organizing fibrotic stroma in these tumors ...
www.biorxiv.org
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 12d
💪💪💪
shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
And a special thank you to the amazing Shachaf Frenkel, Avi Mayo, and Itay Ben Shalom from
@urialonlab.bsky.social lab!!!
shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
Extended thanks to Eviatar Weizman, Yaniv Stein, Kfir Baruch Umansky, @jacobelk.bsky.social, @shimritmayer.bsky.social and Miri Adler @hebrewuniversity.bsky.social 🙏
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
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🇨🇦🦾🦾🦾
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
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)🇺🇸
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
Huge thanks to the LUSC patients who generously contributed samples, who made this project possible🫁
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
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)
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
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
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
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
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
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
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
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...
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
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
Interestingly, while the fibrotic stroma is ❄️cold, the adaptive immune microenvironment remains “hot,” with enriched T and B cells
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
We find that LUSC tumors show a ❄️cold fibrotic architecture: macrophages are depleted while fibroblasts are dramatically elevated
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
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...
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
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
LUSC often presents with desmoplastic, ECM-rich regions and has proven largely refractory to targeted therapies
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
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
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
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
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
And most recently in Crohn’s disease
academic.oup.com/ecco-jcc/art...
Validate User
academic.oup.com
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
It was further validated in the context of kidney fibrosis
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
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
Recently, we validated this model in the context of acute (myocardial infarction) and chronic (heart failure) cardiac injuries
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
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
In 🔥 hot fibrosis, macrophages and fibroblasts reciprocally support each other. In ❄️ cold fibrosis, fibroblasts go solo, sustaining themselves through an autocrine growth factor loop
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
The theoretical model predicts 2 fibrotic states:
❄️ cold and 🔥 hot fibrosis
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
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...
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
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
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.
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shovalmiyara.bsky.social
Shoval Miyara @shovalmiyara.bsky.social · 16d
🚨It’s here! Our new preprint is live on bioRxiv🚨
A fibroblast-centric network drives ❄️cold fibrosis in the tumor microenvironment of lung squamous cell carcinoma 🧵
www.biorxiv.org/content/10.1...
A fibroblast-centric network drives cold fibrosis in the tumor microenvironment of lung squamous cell carcinoma
The tumor microenvironment (TME) of chronic inflammation-associated cancers (CIACs) is shaped by cycles of injury and maladaptive repair, yet the principles organizing fibrotic stroma in these tumors ...
www.biorxiv.org
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