Simon Mitchell

New paper led by @ejayawant.bsky.social 🎉
We review:
- how computational biology is helping us understand lymphoma,
- how machine learning and cell simulations make sense of vast amounts of data,
- how models can personalise treatments to each person with lymphoma.
portlandpress.com/biochemsoctr...

Artist’s blood cancer treatment inspires powerful new exhibition at University of Brighton A University of Brighton graduate has turned his own cancer journey into a striking art installation exploring illness and the duality of medical treatment.

Artist’s blood cancer treatment inspires powerful new exhibition at University of Brighton, @bsmsmedschool.bsky.social

www.brighton.ac.uk/news/2025/ar...

jobs — Sussex Cancer Research Centre

Multiple positions currently open for applications but with imminent dealines:
- PhD studentship with Sally Wheelwright on cancer-related fatigue.
- PhD studentship with Chris Pepper on multiple myeloma.
- Postdoc with @mitchell.science
on cancer systems biology.
sussexcancer.org/jobs

Recruiting for a post doc on a UKRI Future Leaders fellowship project | Mitchell Lab We are really excited to be advertising for an enthusiastic and committed post doc to work on a wet lab/dry lab project applying systems biology to mulitple diseases. Deadline 29th June.

Excited to announce that thanks to securing a UKRI FLF follow-on award (mitchell.science/talk/566k-fo...)
✨We are hiring✨
3-year systems biology (wet/dry) postdoc, to pioneer new approaches to personalised medicine.
Learn more + apply (before 29 June):
mitchell.science/talk/recruit...

Plz share

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🔬 A postdoc in numbers (and life beyond the lab)
As I wrap up my postdoc with @mitchell.science at @bsmsmedschool.bsky.social, I've been reflecting on everything that’s changed since I started in 2021. A lot can happen in a few years…

so lovely to be at @cshlnews.bsky.social for the Systems Immunology Meeting.
Great venue and even better science.

Congrats Okan!

I’m using the old “stand one step down” trick here.

I will be talking about our new cancer genomics toolkit DepMine at the first meeting of the @sussexcancer.org Sussex Cancer Research Centre Computational Biology Group today - new career trajectory ok so far 🤞

BBC News, South East covers Words from the Waiting Room. — Sussex Cancer Research Centre Creative Community Engagement project led by Deborah Humphrey, and Karina Patfield highlighted on BBC news. Words from the Waiting Room offers cancer patients, survivors, and supporters a safe enviro...

Exciting to see SCRC Creative Community Engagement project led by Deborah Humphrey, and Karina Patfield, highlighted on BBC news.
"Words from the Waiting Room offers cancer patients, survivors, and supporters a safe environment to express themselves"
sussexcancer.org/news/bbc-new...

Custom artwork, lightning lecture competition, new theme launch, and exciting events. Reminder: studentship deadline 24th March, computational and brain tumour meetings, creative community engagement.

Latest newsletter:
- PhD studentships deadline: 24th March
- Kick-off of the SCRC Computational Cancer Research themed meetings
- Sussex Brain Tumour Research launch
- Custom artwork inspired by your research
- Lightning lecture competition
And more!
sussexcancer.curated.co/issues/9#start

Also good for reducing excess iron, free radicals, and therefore DNA damage which leads to cancer.

Proud moment from Arran Pack's graduation.
It's so rewarding to see our lab's first PhD student graduate, and I couldn't have asked for a better first student.
Job well done Arran!
🤜🤛

🎓Graduation news! 🎓

Some of the HaemTeam were at @bsmsmedschool.bsky.social graduation this week celebrating new Drs. The @andreapepper.bsky.social @chrispepper68.bsky.social team were celebrating Eleni Ladikou and Kim Sharp PhD graduation, whilst @mitchell.science were toasting Arran Pack grad!

Updates from the Sussex Cancer Research Centre on World Cancer Day. — Sussex Cancer Research Centre The theme of World Cancer Day 2025 is “United by Unique”, which places people at the centre of care and their stories at the heart of the conversation. Today the Sussex Cancer Research Centre (SCR...

It is #WorldCancerDay
We are excited to announce our funded research projects, a new community engagement strategy, creative award winners, and interviews.

sussexcancer.org/news/announc...

@bsmsmedschool.bsky.social @sussexuni.bsky.social @uniofbrighton.bsky.social @eshtnhs.bsky.social

Trump hits NIH with ‘devastating’ freezes on meetings, travel, communications, and hiring Researchers facing “a lot of uncertainty, fear, and panic”

This is devastating.
Grant review panels not meeting completely halts scientific progress
3 people at the inauguration had their wealth increase by $233 billion between them since the election, while scientists and people with disease are abandoned.
www.science.org/content/arti...

New position available: Research Fellow in Cancer Studies!
Work on a cutting edge research project funded by @bloodcanceruk.bsky.social.
Applications close on January 26th.
www.SussexCancer.org/jobs

What unique insights can modeling approaches capture about the immune system? The immune system, optimized by evolution to maintain health and prevent disease, is remarkably good at what it does. It detects pathogens and monitors physiological stresses with a sensitivity and selectivity that far surpasses that of man-made biosensors. It then mounts potent yet precise responses, enabling the body to maintain homeostasis amid varying internal milieu and external threats.

Thoughts from leaders of systems #immunology how mechanistic models can leverage omics/ML for deeper understanding of how our immune system works #sysbio @cp-cellsystems.bsky.social
www.cell.com/cell-systems...

A minimum parsimony speciation tree.

Do you like trees? Fancy quantifying tree shapes in terms of diversity, balance, average outdegree, etc. so you can compare them with each other or with models? Even if they have very different leaf counts? And accounting for branch lengths and polytomies? We have an easy solution for you.

1/n

Well deserved! Congrats Rhys

Summary:
1. Combining models with molecular "fingerprinting" can match DLBCL with the right drugs.
2. This can overcome lymph node-mediated drug resistance.
3. cRel can be activated by crosstalk from the non-canonical pathway and induce MCL1.
3. Aimilia Vareli is awesome!

Yes!
Non-canonical NF-kB inhibition with Amgen16 overcomes all the microenvrionment mediated resistance we discovered, regardless of the mechanism!
@amgen.bsky.social

Let's summarise...

So, taking a step back, we have:
- Different Achilles heel in each DLBCL
- Different resistance mechanism mediated by complicated cross talk.
This makes it really hard to improve treatments.
We asked if we could break all the links with the TME by inhibiting non-canonical NF-kB?

ChIPseq says yes, but we needed another test.
The model told us an IkBe knockout would selectively upregulate cRel, which would upregulate MCL1 if we were right.
Collaborating with Alexander Hoffmann's group we tested this in IkBe KO mice.
cRel and MCL1 go up!

Imaging confirms it!
Chronic NF-kB activation creates crosstalk between the pathways.
We also knew this chronic NF-kB was causing the drug resistance, because when we inhibit it (with ibrutinib) we can re-sensitize the cells.
But the link between cRel and MCL1 is new.
Is it real?

Enter computational modelling.
A model developed by Arran Pack
predicted that the high RelA could create cross talk between the NF-kB pathways.
CD40 -> NIK -> cRel -> MCL1?
Soumen Basak has seen this before in healthy B-cells. We predict it's happening in DLBCL.
Let's check

We knew the MCL1 was probably NF-kB's fault, isn't everything ;)
We used imaging to find which NF-kB components were in the nucleus before the cells went into co-culture.
Lots of RelA in cells that induce MCL1.
But how does high RelA in monoculture lead to MCL1 in co-culture?

The co-culture effect was seen in multiple cell lines, to drugs targetting BCL2 and BCLXL. This might explain why these drugs work in the lab but not in DLBCL patients.
Some of this we understood:
CD40 -> NIK -> RelB -> BCLXL
But some really did not:
CD40 -> NIK -> ? -> MCL!?

We used a co-culture system that mimicks how T-cells support DLBCL cells in lymph nodes.
This made both cell populations resist treatment. They upregulated BCLXL which compensates for BCL2 inhibition.
Inherent resistance, and micro-environmental resistance in one cell line.
Neat

We find the two cell populations in the same cell line have totally different inherent sensitivity to BCL2 inhibition!
Why?
One has high MCL1 to compensate for BCL2 inhibition.
This is cool, but these are cells in a dish. Could we still drug these in a supportive lymph node?

Do these fingerprints predict drug responses?
Yes!
But what is going on with the U2932 cell line? Like lots of cancer it contains multiple cell populations with different genetics.
This makes it great for figuring out how different cells in the same tumour might respond to a drug.