Simon Richardson

The Finlay Family Bursary for Scottish undergraduates We are proud to offer this bursary to encourage Scottish students to apply for, and take up, the offer of an undergraduate place at St Catharine’s – an opportunity which would normally involve greater financial cost than attending a Scottish university.

💙 Between now & the UCAS application deadline on 15 Oct, it’s worth checking if you're eligible for the Finlay Family Bursary, which covers all tuition fees & a living allowance for a St Catharine’s student from Scotland for all 3 or 4 years of an undergraduate degree: shorturl.at/K0RuE 3/3

LS, an emergent form of acute leukemia relapse after antigen-targeted therapy, primarily in B-ALL, has dismal outcomes. buff.ly/59xI6qv #hemesky

Congrats! Really exciting work.

I feel a student granulomatous round of unknown aetiology coming on.

I’m looking for a Postdoc to join my new lab @pdncambridge.bsky.social on an MRC-funded project and explore maternal inter-organ communication with a focus on the mammary gland, using a novel mouse model.

📍 Tenure: 3 years
⏳ Deadline: 15 August 2025

Please RT 🙏
👉 www.jobs.cam.ac.uk/job/51984/

No trains? No problem! Wacky races down to The City of London with these amazing @crukcamcentre.bsky.social entrepreneurial scientists just in time for the CRUK Innovation and Enterprise awards. Thank you @crhorizons.bsky.social 🥂🎉🙏

Absolute honour to attend Marc Mansour’s @marcmansour.bsky.social inaugural lecture at ICH today. An inspiring clinician scientist and all round legend. #researchculture

Fabulous news Geula. Congratulations!! 🥂

Really exciting to co-organise the 20 year graduation reunion for Oxford medical school last night. Wonderful to reunite with old friends and hear retired DoS Tim Lancaster speak powerfully about how caring is at the heart of good medicine 💊❤️

Best night of the year !

Farewell dinner for the new doctors from @stcatharines.bsky.social

Interviewed them 7 years ago.
Watched them blossom for 6 years.
Now they’re amazing!

Thanks to the editorial team @natcomms.nature.com for including our recent paper in their Editors' Highlights in the field of Cancer Biology 🎉

Two charts present survival rates for childhood leukemia over time, specifically focusing on Acute Lymphoblastic Leukemia (ALL) and Acute Myeloid Leukemia (AML). In the top panel, for ALL, a series of curved lines represent overall survival rates plotted against years since diagnosis. The lines show a marked increase in survival rates from the late 1960s, when only 14% of children survived more than five years post-diagnosis, to around 94% in the 2010s. Key intervals are labeled, with different colors indicating different periods of diagnosis, ranging from 1972-1975 to 2010-2015. The bottom panel illustrates survival rates for AML, which are consistently lower overall compared to ALL. Like the top graph, it features several colored lines indicating specific periods. The highest point noted indicates a survival rate of 65%. The graph captures trends in survival as well, showing gradual improvement over time, from 1975-1977 up to 2011-2017. Data sources for these visualizations are cited at the bottom: Mignon Loh et al. (2023) for ALL and Todd M Cooper et al. (2023) for AML, both from the Children's Oncology Group. The chart is published by Our World in Data, and licensed under Creative Commons by the author, Saloni Dattani.

I wrote a new piece on how much progress has been made in treating childhood leukemia.

The answer is: quite a lot!

Before the 1970s, fewer than 10% of children diagnosed survived 5 years after diagnosis.

Now most are cured and around 85% survive that long.
ourworldindata.org/childhood-le...

What an inspiring evening hearing from patients, researchers and fundraisers at an Evening with Leukaemia UK.

So much progress. So much to do
@leukaemiauk.bsky.social

Dual drug approach shows promise against childhood cancer On the B-ALL...

Thanks to Chris Smith and the Naked Scientists for the invitation to discuss our work - fully clothed 🤓

www.thenakedscientists.com/articles/int...

And that’s a wrap. 20 supervisons in biochemistry and genetics for the Catz @stcatharines.bsky.social first year medics. Good luck in the exams!

12/12 Special thanks to the patient donors and samples from VIVO Biobank and of course Brian Huntly & group 🤗 #CSCI @crukcamcentre.bsky.social | Work in my group is largely funded by Cancer Research UK #CRUK, Leukaemia UK
@leukaemiauk.bsky.social‬ and the European Hematology Association. 🙏🏻

11/12 Lots of thanks for help with this multidisciplinary project, including to stellar PhD Alicia Garcia-Gimenez and RA Jon Ditcham for all their hard work | to amazing collaborators @koulman.bsky.social @mitoredox.bsky.social @marcmansour.bsky.social

10/12 Excitingly, the CREBBP inhibitor Inobrodib has already been tested in combination with Venetoclax in AML, confirming safety. We therefore think this could be a novel, safe, oral approach that could complement current chemo- and immunotherapies, improving outcomes and reducing toxicity.

9/12 The results almost perfectly replicated the findings in our genetic model, confirming marked sensitisation or synergy between CREBBP and BCL2 inhibitors in cell line and PDX models in vitro and in vivo.

8/12 Only 20% of patient have a CREBBP mutation at relapse, yet this is a very strong mechanism. We therefore tested whether pharmacological inhibitors of CREBBP can sensitise B-ALL to Venetoclax, irrespective of genetic subtype.

7/12 Interestingly, these changes can also be seen in patients – TARGET RNAseq data showed that low expression of CREBBP strongly correlates with dysregulation of ether-linked lipid pathways and up-regulation of redox scavengers.

6/12 Transcriptional, proteomic and lipidomic analysis of our cell line models showed up-regulation of redox-protective pathways, alongside changes in lipids, including low levels of peroxisomal/ER ether-linked lipids, and high levels of ferroptosis-susceptible membrane PUFAs.

5/12 The known mechanism of BCL2 inhibitors is to induce apoptotic programmed cell death, but at low dose in our sensitive cell lines, the predominant form of cell death turned out to be ferroptosis. Why…?

4/12 Targeted drug screening on these lines showed that CREBBP mutations potently sensitised the B-ALL cell lines to the BCL2 inhibitor Venetoclax, with up to a 1000x change in lethal dose.

3/12 We used CIRPSR to genetically-engineer B-ALL cell lines that only differed in the presence or absence of various CREBBP mutations. The result: CREBBP loss reduced gene transcription, and phenotypically resulted in higher levels of metabolism and a paradoxical *slowing* of cell cycle.

2/12 CREBBP mutations are associated with high-risk and chemoresistance in B-ALL, and are enriched at relapse. We wanted to understand what CREBBP is doing in B-ALL and identify novel drugs to treat these high-risk patients.

1/12 TL:DR: Genetic or pharmacological inhibition of CREBBP function can sensitise early B cells to BCL2 inhibitors - not by apoptosis, but *ferroptotic* programmed cell death.

CREBBP inactivation sensitizes B cell acute lymphoblastic leukemia to ferroptotic cell death upon BCL2 inhibition - Nature Communications CREBBP mutations in B-cell acute lymphoblastic leukemia (B-ALL) are linked to poor prognosis and chemoresistance. Here, the authors show that genetic or pharmacological inactivation of CREBBP sensitiz...

Delighted that our work describing a potential novel treatment approach for B-cell Acute Lymphoblastic Leukaemia is published today in @natcomms.nature.com‬. 🧵

www.nature.com/articles/s41...

Prof. Stefan Marciniak, Sir John Benger, Lord Vallance, Prof. Patrick Maxwell, Prof. Dame Jean Thomas and Prof. Sir Keith Peters in Main Court at St Catharine's College

We were delighted to welcome Lord Vallance, Minister of State for Science, last week. Hala Al-Haboubi (a 3rd-year medical student at Catz) said, "Lord Vallance shared inspirational, forward-looking insights about the future of scientific research. It was a real privilege to hear from him!" 1/3

Merci bien #SFH for the invitation to present our science and plans for an early phase clinical trial in #BALL in wonderful Paris. ❤️@crukcamcentre.bsky.social