Chris Tape

Why do COX-inhibitors like aspirin and celecoxib help prevent and treat colorectal cancer (CRC)? Our new preprint suggests part of the answer is that they work as ‘anti-plasticity’ drugs. (1/7) www.biorxiv.org/content/10.6...

Together, we propose a causal, spatial mechanism for how inflammatory stromal niches grant non-genetic access to therapy-resistant, metastatic cell fates — and a mechanistic rationale for COX inhibition (aspirin/celecoxib) in both preventing and treating CRC. (7/7)

Why do COX-inhibitors like aspirin and celecoxib help prevent and treat colorectal cancer (CRC)? Our new preprint suggests part of the answer is that they work as ‘anti-plasticity’ drugs. (1/7) www.biorxiv.org/content/10.6...

Full factorial analysis revealed that PGE2 is the dominant CAF regulator of CRC cell-fate. PGE2 rapidly and reversibly converts chemosensitive proliferative colonic stem cells (proCSCs) into chemorefractory, pro-metastatic revival colonic stem cells (revCSCs). (5/7)

Why do COX-inhibitors like aspirin and celecoxib help prevent and treat colorectal cancer (CRC)? Our new preprint suggests part of the answer is that they work as ‘anti-plasticity’ drugs. (1/7) www.biorxiv.org/content/10.6...

We developed a way to quantify CAF-induced plasticity in CRC epithelia and found that the transcriptional co-repressor DACH1 marks which cells are susceptible to CAFs: DACH1+ epithelia respond to stromal signals, DACH1– epithelia don't. (3/7)

Why do COX-inhibitors like aspirin and celecoxib help prevent and treat colorectal cancer (CRC)? Our new preprint suggests part of the answer is that they work as ‘anti-plasticity’ drugs. (1/7) www.biorxiv.org/content/10.6...

In early-2025 I was reeling from a ‘scored fundable’ grant application that was not funded. I really believed in this grant and knew the ideas were good but the review panel just weren’t into the project and there nothing more I could do. That’s science, but it hurts. (1/8)

In December we pitched the project to the Cancer Grand Challenge committee in New York. At this point we’d spent so much time together that the team felt like a scientific family and I think that came across during the interview. (7/8)

In early-2025 I was reeling from a ‘scored fundable’ grant application that was not funded. I really believed in this grant and knew the ideas were good but the review panel just weren’t into the project and there nothing more I could do. That’s science, but it hurts. (1/8)

We brought together world-leaders in signalling activators (Bill Sellers, Roger Williams, Madelon Maurice, Steve Wedge) with experts in cancer cell models and signalling dynamics (Karuna Ganesh, Vivian Li, Smita Krishnaswamy) to form team REWIRE-CAN. (5/8)

In early-2025 I was reeling from a ‘scored fundable’ grant application that was not funded. I really believed in this grant and knew the ideas were good but the review panel just weren’t into the project and there nothing more I could do. That’s science, but it hurts. (1/8)

Our idea was to use novel ‘activator’ drugs to ‘re-wire’ cancer cell signalling. This new class of therapies aim to turn the extreme signalling dependencies of cancer cells against them by hyper-activating signalling. We could also use activators to move cancer cells into vulnerable states. (3/8)

In early-2025 I was reeling from a ‘scored fundable’ grant application that was not funded. I really believed in this grant and knew the ideas were good but the review panel just weren’t into the project and there nothing more I could do. That’s science, but it hurts. (1/8)

Excited to share our new paper: ‘Phenoscaping Reveals Multimodal γδ T-cell Cytotoxicity as a Strategy to Overcome Cancer Cell–Mediated Immunomodulation’ led by Callum Nattress in collab. with Jonathan Fisher lab (1/13) aacrjournals.org/cancerres/ar...

PDO scRNA-seq data can be found here: zenodo.org/records/1582...

Excited to share our new paper: ‘Phenoscaping Reveals Multimodal γδ T-cell Cytotoxicity as a Strategy to Overcome Cancer Cell–Mediated Immunomodulation’ led by Callum Nattress in collab. with Jonathan Fisher lab (1/13) aacrjournals.org/cancerres/ar...

This project was an experimental tour de force from Callum Nattress, Rhianna O'sullivan, Daniel Fowler, Colin Hutton, Petra Vlckova, @vivianlilab.bsky.social, Kerry Chester, John Anderson, @marta-barisa.bsky.social, and Jon Fisher. Thanks to @cruk-cityoflondon.bsky.social for funding. (13/13)

Excited to share our new paper: ‘Phenoscaping Reveals Multimodal γδ T-cell Cytotoxicity as a Strategy to Overcome Cancer Cell–Mediated Immunomodulation’ led by Callum Nattress in collab. with Jonathan Fisher lab (1/13) aacrjournals.org/cancerres/ar...

This demonstrates that these lethal, chemoresistant revCSCs cancer cells are therapeutically targetable by cellular therapies. (11/13)

Excited to share our new paper: ‘Phenoscaping Reveals Multimodal γδ T-cell Cytotoxicity as a Strategy to Overcome Cancer Cell–Mediated Immunomodulation’ led by Callum Nattress in collab. with Jonathan Fisher lab (1/13) aacrjournals.org/cancerres/ar...

To confirm that the anti-B7-H3 antibody was only inducing ADCC and not invoking the putative immune checkpoint properties of B7-H3, we also demonstrated that only a complete IgG — and not an Fc-null IgG — could trigger multimodal killing. (9/13)

Excited to share our new paper: ‘Phenoscaping Reveals Multimodal γδ T-cell Cytotoxicity as a Strategy to Overcome Cancer Cell–Mediated Immunomodulation’ led by Callum Nattress in collab. with Jonathan Fisher lab (1/13) aacrjournals.org/cancerres/ar...

We found that γδ T cells can kill both MSS and MSI CRC PDOs. However, when γδ T cells only use AIC, γδ T cell signalling converges on the target PDO, irrespective of T-cell donor. This suggests that γδ T cells are immunomodulated by PDOs and ITH is dominant over IDH. (7/13)

Excited to share our new paper: ‘Phenoscaping Reveals Multimodal γδ T-cell Cytotoxicity as a Strategy to Overcome Cancer Cell–Mediated Immunomodulation’ led by Callum Nattress in collab. with Jonathan Fisher lab (1/13) aacrjournals.org/cancerres/ar...

Next, we found that stIL15-engineered γδ T cells can rapidly kill MSI colorectal cancer (CRC) patient-derived organoids (PDOs) in 3D via AIC. Killing could be further increased by inducing ADCC via a novel anti-B7-H3 antibody — demonstrating multimodal cytotoxicity. (5/13)

Excited to share our new paper: ‘Phenoscaping Reveals Multimodal γδ T-cell Cytotoxicity as a Strategy to Overcome Cancer Cell–Mediated Immunomodulation’ led by Callum Nattress in collab. with Jonathan Fisher lab (1/13) aacrjournals.org/cancerres/ar...

To explore this, we performed a systematic single-cell phenoscaping study of >1,000 organoid cultures testing the combinatorial interactions between γδ T cell killing modalities (AIC vs ADCC), γδ T cell inter-donor heterogeneity, and cancer cell inter-tumour heterogeneity. (3/13)

Excited to share our new paper: ‘Phenoscaping Reveals Multimodal γδ T-cell Cytotoxicity as a Strategy to Overcome Cancer Cell–Mediated Immunomodulation’ led by Callum Nattress in collab. with Jonathan Fisher lab (1/13) aacrjournals.org/cancerres/ar...