Lee Machado
@drleemachado.bsky.social
Professor of Molecular Medicine @uninorthants researching #infection, #immunity and #cancer. Deputy Chair @BeaCitySixth
Looking forward to popping over for a nose at some point! 😉
October 27, 2025 at 9:16 PM
Looking forward to popping over for a nose at some point! 😉
Reposted by Lee Machado
Read the associated research article here: www.nature.com/articles/s41...
Epstein–Barr virus exploits desmocollin 2 as the principal epithelial cell entry receptor - Nature Microbiology
A genome-wide CRISPR screen helps to identify the Epstein–Barr virus receptor desmocollin 2 for primary epithelial cell infection. Additional infection assays revealed that desmocollin 3 also aids infection.
www.nature.com
October 1, 2025 at 5:55 PM
Read the associated research article here: www.nature.com/articles/s41...
8/8 Key message:
🧬 DMD is not uniformly oncogenic or tumour suppressive.
🧩 Isoform Dp71ab may be central.
📈 Any therapeutic approach must consider tumour context.
febs.onlinelibrary.wiley.com/doi/10.1002/...
🧬 DMD is not uniformly oncogenic or tumour suppressive.
🧩 Isoform Dp71ab may be central.
📈 Any therapeutic approach must consider tumour context.
febs.onlinelibrary.wiley.com/doi/10.1002/...
FEBS Press
We propose a context-dependent model where the Duchenne muscular dystrophy (DMD) gene acts as a tumour suppressor in aggressive tumours and as an oncogene in less aggressive ones. We propose this mod...
febs.onlinelibrary.wiley.com
August 21, 2025 at 12:48 PM
8/8 Key message:
🧬 DMD is not uniformly oncogenic or tumour suppressive.
🧩 Isoform Dp71ab may be central.
📈 Any therapeutic approach must consider tumour context.
febs.onlinelibrary.wiley.com/doi/10.1002/...
🧬 DMD is not uniformly oncogenic or tumour suppressive.
🧩 Isoform Dp71ab may be central.
📈 Any therapeutic approach must consider tumour context.
febs.onlinelibrary.wiley.com/doi/10.1002/...
7/8 For me, this project reflects pivoting in research. Learning bioinformatics during COVID provided the tools to take this forward, and collaborating with @Weekademia, it has now matured into a published study and a new framework to functionally test.
August 21, 2025 at 12:48 PM
7/8 For me, this project reflects pivoting in research. Learning bioinformatics during COVID provided the tools to take this forward, and collaborating with @Weekademia, it has now matured into a published study and a new framework to functionally test.
6/8 Supporting evidence:
Aggressive cancers often downregulate/mutate DMD.
Less aggressive cancers retain intact DMD.
So, DMD’s role is context-dependent.
Aggressive cancers often downregulate/mutate DMD.
Less aggressive cancers retain intact DMD.
So, DMD’s role is context-dependent.
August 21, 2025 at 12:48 PM
6/8 Supporting evidence:
Aggressive cancers often downregulate/mutate DMD.
Less aggressive cancers retain intact DMD.
So, DMD’s role is context-dependent.
Aggressive cancers often downregulate/mutate DMD.
Less aggressive cancers retain intact DMD.
So, DMD’s role is context-dependent.
5/8 From this, we propose a dual model:
In aggressive cancers, DMD acts as a tumour suppressor.
In less aggressive cancers, DMD can play an oncogenic role.
In aggressive cancers, DMD acts as a tumour suppressor.
In less aggressive cancers, DMD can play an oncogenic role.
August 21, 2025 at 12:48 PM
5/8 From this, we propose a dual model:
In aggressive cancers, DMD acts as a tumour suppressor.
In less aggressive cancers, DMD can play an oncogenic role.
In aggressive cancers, DMD acts as a tumour suppressor.
In less aggressive cancers, DMD can play an oncogenic role.
4/8 Pathway analysis revealed two contrasting patterns:
High DMD protective → ECM integrity & adhesion preserved.
High DMD harmful → morphogenesis & cellular plasticity promoted.
High DMD protective → ECM integrity & adhesion preserved.
High DMD harmful → morphogenesis & cellular plasticity promoted.
August 21, 2025 at 12:48 PM
4/8 Pathway analysis revealed two contrasting patterns:
High DMD protective → ECM integrity & adhesion preserved.
High DMD harmful → morphogenesis & cellular plasticity promoted.
High DMD protective → ECM integrity & adhesion preserved.
High DMD harmful → morphogenesis & cellular plasticity promoted.
3/8 Isoform analysis was crucial:
Dp71ab was the dominant transcript and mirrored survival patterns.
Dp40 also appeared consistently.
This suggests isoforms, not just total DMD drive the biology.
Dp71ab was the dominant transcript and mirrored survival patterns.
Dp40 also appeared consistently.
This suggests isoforms, not just total DMD drive the biology.
August 21, 2025 at 12:48 PM
3/8 Isoform analysis was crucial:
Dp71ab was the dominant transcript and mirrored survival patterns.
Dp40 also appeared consistently.
This suggests isoforms, not just total DMD drive the biology.
Dp71ab was the dominant transcript and mirrored survival patterns.
Dp40 also appeared consistently.
This suggests isoforms, not just total DMD drive the biology.
2/8 Using TCGA data (33 cancers), we found DMD expression significantly linked to survival in 9 cancers.
But the direction split:
High DMD = ⬆️ survival (breast, lung, pancreas, AML, uveal melanoma)
High DMD = ⬇️ survival (glioma, thymoma, kidney and rectal)
But the direction split:
High DMD = ⬆️ survival (breast, lung, pancreas, AML, uveal melanoma)
High DMD = ⬇️ survival (glioma, thymoma, kidney and rectal)
August 21, 2025 at 12:48 PM
2/8 Using TCGA data (33 cancers), we found DMD expression significantly linked to survival in 9 cancers.
But the direction split:
High DMD = ⬆️ survival (breast, lung, pancreas, AML, uveal melanoma)
High DMD = ⬇️ survival (glioma, thymoma, kidney and rectal)
But the direction split:
High DMD = ⬆️ survival (breast, lung, pancreas, AML, uveal melanoma)
High DMD = ⬇️ survival (glioma, thymoma, kidney and rectal)
1/8 The Duchenne muscular dystrophy gene (DMD) is well known in muscle biology, but in cancer its role has been puzzling.
Some studies showed high DMD = better survival. Others showed the opposite.
We set out to explain why.
Some studies showed high DMD = better survival. Others showed the opposite.
We set out to explain why.
August 21, 2025 at 12:48 PM
1/8 The Duchenne muscular dystrophy gene (DMD) is well known in muscle biology, but in cancer its role has been puzzling.
Some studies showed high DMD = better survival. Others showed the opposite.
We set out to explain why.
Some studies showed high DMD = better survival. Others showed the opposite.
We set out to explain why.