Philip Dunne
@drpipdunne.bsky.social
Phenotypic plasticity in colorectal cancer. Group leader at QUB Belfast and CRUK Scotland Institute.
CRUK-SI: https://tinyurl.com/5fr9n2ew
QUB: https://tinyurl.com/4b68vf56
CRUK-SI: https://tinyurl.com/5fr9n2ew
QUB: https://tinyurl.com/4b68vf56
Sunshine and science in Glasgow today at the CRC-STARS kick off meeting
Excellent presention from Raheleh in our team charting phenotypic evolution during cancer development and progression, and how best we can use preclinical models of cancer to improve patient outcomes
Excellent presention from Raheleh in our team charting phenotypic evolution during cancer development and progression, and how best we can use preclinical models of cancer to improve patient outcomes
May 14, 2025 at 11:56 AM
Sunshine and science in Glasgow today at the CRC-STARS kick off meeting
Excellent presention from Raheleh in our team charting phenotypic evolution during cancer development and progression, and how best we can use preclinical models of cancer to improve patient outcomes
Excellent presention from Raheleh in our team charting phenotypic evolution during cancer development and progression, and how best we can use preclinical models of cancer to improve patient outcomes
AACR.. over and out! Great couple of days in Chicago, brilliant to catch up with so many collaborators and make new connections. Coming home brimming with new ideas to take into our @cruk-si.bsky.social early detection, @incise-research.bsky.social, & CRC-STARS programmes
#AACR25
#AACR25
April 30, 2025 at 8:45 PM
AACR.. over and out! Great couple of days in Chicago, brilliant to catch up with so many collaborators and make new connections. Coming home brimming with new ideas to take into our @cruk-si.bsky.social early detection, @incise-research.bsky.social, & CRC-STARS programmes
#AACR25
#AACR25
Incredibly proud to see Dr Fisher presenting her research at the @theaacr.bsky.social annual conference.
Understanding precancer biology is crucial for improving early detection, and preventing early cancer development and progression.
#AACR25
@nataliefisher.bsky.social
Understanding precancer biology is crucial for improving early detection, and preventing early cancer development and progression.
#AACR25
@nataliefisher.bsky.social
April 30, 2025 at 3:56 AM
Incredibly proud to see Dr Fisher presenting her research at the @theaacr.bsky.social annual conference.
Understanding precancer biology is crucial for improving early detection, and preventing early cancer development and progression.
#AACR25
@nataliefisher.bsky.social
Understanding precancer biology is crucial for improving early detection, and preventing early cancer development and progression.
#AACR25
@nataliefisher.bsky.social
Session with Natalie’s talk starting shortly in room E351
April 29, 2025 at 7:12 PM
Session with Natalie’s talk starting shortly in room E351
If you are Chicago bound watch out for Natalie & Sid presenting at #AACR2025 & come say hello!
Natalie's @theaacr.bsky.social Women in Cancer Research award talk covers how we can use biology to improve early detection of polyps
Sid's poster is on early tumour transcriptional landscapes
Natalie's @theaacr.bsky.social Women in Cancer Research award talk covers how we can use biology to improve early detection of polyps
Sid's poster is on early tumour transcriptional landscapes
April 24, 2025 at 9:39 AM
If you are Chicago bound watch out for Natalie & Sid presenting at #AACR2025 & come say hello!
Natalie's @theaacr.bsky.social Women in Cancer Research award talk covers how we can use biology to improve early detection of polyps
Sid's poster is on early tumour transcriptional landscapes
Natalie's @theaacr.bsky.social Women in Cancer Research award talk covers how we can use biology to improve early detection of polyps
Sid's poster is on early tumour transcriptional landscapes
Massive congratulations to Dr Natalie Fisher working within @incise-research.bsky.social with @joedwardswwcrc.bsky.social across @qubelfastofficial.bsky.social @cruk-si.bsky.social on being awarded an AACR-Woman in Cancer Research Scholar Award and selected for a talk at AACR conference
February 18, 2025 at 10:21 PM
Massive congratulations to Dr Natalie Fisher working within @incise-research.bsky.social with @joedwardswwcrc.bsky.social across @qubelfastofficial.bsky.social @cruk-si.bsky.social on being awarded an AACR-Woman in Cancer Research Scholar Award and selected for a talk at AACR conference
Study supported from a range of funders, including @cancerresearchuk.org
December 6, 2024 at 5:06 PM
Study supported from a range of funders, including @cancerresearchuk.org
Massive congrats again to the team, and Shania Corry who led this study with Svetlana and Noha, working across our Belfast team alongside Glasgow and Galway
(no one on bluesky yet!)
(no one on bluesky yet!)
December 6, 2024 at 5:06 PM
Massive congrats again to the team, and Shania Corry who led this study with Svetlana and Noha, working across our Belfast team alongside Glasgow and Galway
(no one on bluesky yet!)
(no one on bluesky yet!)
So now we can see the full circle of activation that underpins the therapeutic value of polyI:C in stroma-rich tumours.
This patient group has the highest risk of disease relapse and unfortunately does not response to current 5FU-based therapies
So a BIG opportunity here
This patient group has the highest risk of disease relapse and unfortunately does not response to current 5FU-based therapies
So a BIG opportunity here
December 6, 2024 at 5:06 PM
So now we can see the full circle of activation that underpins the therapeutic value of polyI:C in stroma-rich tumours.
This patient group has the highest risk of disease relapse and unfortunately does not response to current 5FU-based therapies
So a BIG opportunity here
This patient group has the highest risk of disease relapse and unfortunately does not response to current 5FU-based therapies
So a BIG opportunity here
The cancer stem cells associated with CMS1 were more inflammation-induced (good) and those in CMS4 were more stroma-induced (bad)
and using polyI:C we could push cancer stem cells between these states!!
and using polyI:C we could push cancer stem cells between these states!!
December 6, 2024 at 5:06 PM
The cancer stem cells associated with CMS1 were more inflammation-induced (good) and those in CMS4 were more stroma-induced (bad)
and using polyI:C we could push cancer stem cells between these states!!
and using polyI:C we could push cancer stem cells between these states!!
In macrophages, we see a massive & rapid reprogramming towards an M1 (dont call them that near an immunologist!) & proinflammatory state in our lineages and scRNAseq from colorectal tumour associated macrophages
December 6, 2024 at 5:06 PM
In macrophages, we see a massive & rapid reprogramming towards an M1 (dont call them that near an immunologist!) & proinflammatory state in our lineages and scRNAseq from colorectal tumour associated macrophages
We see lots of consistent responses (IFN..), and lineage-specific response (NFkB, TNF..)
but what was most interesting was the contrasting phenotypes this signalling induced prior to the anti-metastatic CD8+ liver response we see at the end
but what was most interesting was the contrasting phenotypes this signalling induced prior to the anti-metastatic CD8+ liver response we see at the end
December 6, 2024 at 5:06 PM
We see lots of consistent responses (IFN..), and lineage-specific response (NFkB, TNF..)
but what was most interesting was the contrasting phenotypes this signalling induced prior to the anti-metastatic CD8+ liver response we see at the end
but what was most interesting was the contrasting phenotypes this signalling induced prior to the anti-metastatic CD8+ liver response we see at the end
Whereas data from the original paper, we had seen that it was the phenotype of the tumour cells and antigen presenting cells in the primary tumour that was critical..
So characterised a panel of these lineages
& see that macrophages love it, but (some) cancer cells not so much
So characterised a panel of these lineages
& see that macrophages love it, but (some) cancer cells not so much
December 6, 2024 at 5:06 PM
Whereas data from the original paper, we had seen that it was the phenotype of the tumour cells and antigen presenting cells in the primary tumour that was critical..
So characterised a panel of these lineages
& see that macrophages love it, but (some) cancer cells not so much
So characterised a panel of these lineages
& see that macrophages love it, but (some) cancer cells not so much
Using the highly-metastatic CMS4 GEMM, KPN (shorturl.at/aTwLE) we see that polyI:C drives a massive influx of CD8+ T-cells in liver mets, and that correlates with tumour burden in the liver
December 6, 2024 at 5:06 PM
Using the highly-metastatic CMS4 GEMM, KPN (shorturl.at/aTwLE) we see that polyI:C drives a massive influx of CD8+ T-cells in liver mets, and that correlates with tumour burden in the liver
We have previously seen that relapse within stroma-rich CMS4 colorectal tumours is strongly associated with an underlying level of interferon activation
which can be therapeutically activated using poly(I:C)..
gut.bmj.com/content/71/12/
which can be therapeutically activated using poly(I:C)..
gut.bmj.com/content/71/12/
December 6, 2024 at 5:06 PM
We have previously seen that relapse within stroma-rich CMS4 colorectal tumours is strongly associated with an underlying level of interferon activation
which can be therapeutically activated using poly(I:C)..
gut.bmj.com/content/71/12/
which can be therapeutically activated using poly(I:C)..
gut.bmj.com/content/71/12/
Massive congrats to Shania, Svetlana & Noha (not on Bsky) identifying the mechanistic and phenotype cascades underpinning the anti-metastatic response triggered by viral mimicry
TLDR; aggressive CMS4 tumours can be reprogrammed towards less aggressive CMS1
biorxiv.org/content/10.1...
thread 👇
TLDR; aggressive CMS4 tumours can be reprogrammed towards less aggressive CMS1
biorxiv.org/content/10.1...
thread 👇
December 6, 2024 at 5:06 PM
Massive congrats to Shania, Svetlana & Noha (not on Bsky) identifying the mechanistic and phenotype cascades underpinning the anti-metastatic response triggered by viral mimicry
TLDR; aggressive CMS4 tumours can be reprogrammed towards less aggressive CMS1
biorxiv.org/content/10.1...
thread 👇
TLDR; aggressive CMS4 tumours can be reprogrammed towards less aggressive CMS1
biorxiv.org/content/10.1...
thread 👇
and thanks to all the co-authors for their contributions to this work!
December 4, 2024 at 4:51 PM
and thanks to all the co-authors for their contributions to this work!
However pairwise and single samples approaches will agree if their is true biological distinction in the two groups you are looking at (Like in our recent PDS subtypes; nature.com/articles/s41...)
December 4, 2024 at 4:51 PM
However pairwise and single samples approaches will agree if their is true biological distinction in the two groups you are looking at (Like in our recent PDS subtypes; nature.com/articles/s41...)
These 3 signatures are the ones that consistently gave the most statistically significant results with all the pairwise GSEA tools, but these signatures are somewhat useless in biologically distinguishing between the very same 2 groups in the same data!!
December 4, 2024 at 4:51 PM
These 3 signatures are the ones that consistently gave the most statistically significant results with all the pairwise GSEA tools, but these signatures are somewhat useless in biologically distinguishing between the very same 2 groups in the same data!!
Well no.. they absolutely dont 😱😱 as the same signatures are entirely overlapping across these same two groups in the same data
December 4, 2024 at 4:51 PM
Well no.. they absolutely dont 😱😱 as the same signatures are entirely overlapping across these same two groups in the same data
While you need to know your groups upfront for pairwise GSEA, single sample GSEA methods allow you to score these same signatures in every tumour sample first, and then group them afterwards..
December 4, 2024 at 4:51 PM
While you need to know your groups upfront for pairwise GSEA, single sample GSEA methods allow you to score these same signatures in every tumour sample first, and then group them afterwards..
This shows us that there are a number of well-understood biologies that are different in relapse v non-relapse tumours - namely interferon signalling (good) and EMT (bad).
In addition, these results are always consistent and highly significant regardless of what GSEA method used
In addition, these results are always consistent and highly significant regardless of what GSEA method used
December 4, 2024 at 4:51 PM
This shows us that there are a number of well-understood biologies that are different in relapse v non-relapse tumours - namely interferon signalling (good) and EMT (bad).
In addition, these results are always consistent and highly significant regardless of what GSEA method used
In addition, these results are always consistent and highly significant regardless of what GSEA method used
Standard pairwise GSEA allows you to identify/confirm biologies that are differentialy enriched in any 2 groups of interest; as an example we use relapse v non-relapse in colorectal cancer
December 4, 2024 at 4:51 PM
Standard pairwise GSEA allows you to identify/confirm biologies that are differentialy enriched in any 2 groups of interest; as an example we use relapse v non-relapse in colorectal cancer
Frosty morning in Belfast, but am sure it will be tropical when I get to Glasgow 🥶
November 18, 2024 at 7:12 AM
Frosty morning in Belfast, but am sure it will be tropical when I get to Glasgow 🥶