I’m delighted to say the Snijder Lab will continue it’s scientific journey at the amazing new Botnar Institute of Immune Engineering dedicated to transforming global child health through immune engineering. I’m incredibly excited about this new part of our discovery journey, and am grateful to all the support from many that have made this possible.
Now out in Nature Medicine✨ Our discovery that an antidepressant (Vortioxetine) is effective against the aggressive primary brain tumor #glioblastoma in patient tissues (ex vivo) and in mouse models.
There’s a lot to unpack here:
👉 Pharmacoscopy predicts clinical response to chemotherapy in glioblastoma, enabling screening of existing neuro-active drugs.
👉 COSTAR: Graph-based in silico drug and mechanism-of-action discovery.
👉 A neural glioblastoma vulnerability on which multiple neuroactive drugs converge.
💫 Most importantly, clinical trials testing Vortioxetine in combination with standard of care are in preparation.
The work was driven by the amazing Dr. Sohyon Lee (starting her own lab at KAIST soon!) and in very close collaboration with Tobias Weiss and Michael Weller from the Universitätsspital Zürich (and many others!). Thank you to the patients and their families for supporting this study, to the key funders European Research Council (ERC) and PHRT – Personalized Health and Related Technologies, and to the many people who have supported and contributed to this study.
For patients or clinicians looking for information on the Vortioxetine clinical trial, please contact Prof. Dr. Michael Weller.
The news response has been quite neat (although not always accurate), some links:
We had an amazing few days in the Austrian alps to get together as a group, and discuss our latest science 🙂 I feel privileged to be able to work with such an amazing group of people!
Did you know that most of the T cells in your blood are Stripy? Stripy T cells (abbreviated as TØ) are small round T cells with a deep nuclear invagination that spatially concentrates the ER, Golgi, mitochondria, and an intracellular pool of T cell receptors. Now, in our latest paper just out in Science, Ben and the team, in collaboration with the wonderful labs from Annette Oxenius and the Blutspende Zurich, show that the way a T cell looks (their “architecture”) matters greatly for its function!
Because of their spatial organization, stripy T cells are fast responders and predominantly turn into effector cells, while conventional looking T cells (abbreviated as TO; i.e. those T cells without nuclear invaginations and therefore without cytoplasmic content bundling) respond slower, more muted, and predominantly give rise to memory precursor cells. Read all about it in Science!
Also check out the ETH News article, the Tweetorial by the lab, and the many amazing videos embedded in the publication, including this one!
This discovery was an unexpected offshoot from our multiplexed immune cell imaging by Yannik previously published in Science Advances and Nature, all funded by the Swiss National Science Foundation ❤️.
🆕 #Pharmacoscopy + #proteotyping + #genetics identifies personalized therapies 🎯💊 for patients suffering from #myelofibrosis, a rare bone marrow blood cancer.
I’m very proud of this work, led by Thijs Wildschut in close collaboration with Bernd Wollscheid & Alexandre Theocharides (University Hospital Zurich) and many others. Funding from the PHRT – Personalized Health and Related Technologies ETH Zürich!
The paper is published open access in Nature Communications.
Amazingly, together with the team of Prof. Dr. Thomas Pabst at the Inselspital Bern, we have successfully completed our second prospective interventional trial!
In the DARTT-1 study (NCT05732688), patients suffering from Acute Myeloid Leukemia (AML) that had exhausted all registered treatment options received pharmacoscopy guided treatment. Strikingly, patients receiving high-scoring treatments lived three times longer (>3x OS) than patients receiving low-scoring treatments.
The study results are published open access in Haematologica. Efforts in the lab were led by teamwork between Yannik Severin, Yasmin Festl, and at the Inselspital by Jonas Schmid.
We’re very proud of Klara’s study, in collaboration with the University Hospital Zurich, now out in Nature Cancer. See also the Research Briefing providing background and comments.
We have followed and analyzed biopsies of a cohort of patients suffering from Multiple Myeloma over several years. Combined pharmacoscopy testing with proteotyping by the Wollscheid Lab reveals the molecular network underlying drug resistance, and shows that pharmacoscopy identifies effective personalized treatments for this complex cancer.
With generous funding from the European Research Council!
Additional reading:
– ETH News post: “How can we fight blood cancer more effectively?“
– MedicalXPress.com: “Testing hundreds of therapeutics outside the body to predict their effectiveness against multiple myeloma“
Yannik’s paper on our single-round multiplexed immunofluorescence assay for the high throughput screening of human immune cells is out in Science Advances! We (sometimes) call the approach Phenoplexing.
The observations stemming from the approach are remarkable: immune cell morphologies reveal an amazing amount of information on the health status of the blood donor, including age, sex, blood pressure, and inflammation.
The approach was first used in Jarrod Shilts’ Nature paper on immune cell wiring diagram.
Please also see this cool write-up at the ETH D-BIOL news & another retweet by Eric Topol :-).
Tim’s study on using deep learning to improve our pharmacoscopy workflows made it to the cover of Blood Cancer Discovery!
Remarkably, we find a strategy for the weakly-supervised label-free detection of healthy and malignant cells in our image-based ex vivo drug screens (pharmacoscopy) leads to better treatment predictions! We call the approach Deep Morphology Learning.
Please see the nice wrap-up on our work at the ETH D-BIOL news.
Additional resources to the paper are provided here.
The Snijder lab contributed to a wonderful study published in Nature, led by Jarrod Shilts and Gavin Wright from the Wellcome Sanger Institute, and in collaboration with others:
A physical wiring diagram for the human immune system | Nature
The study combines careful protein-protein interaction analysis of proteins expressed on the surface of immune cells with pharmacoscopy-based measurement of how those proteins perturb cell-cell contacts among immune cells. On our side, this work was performed by Yannik Severin, using his beautiful single-round multiplexed immunofluorescence protocol to perform image-based screening of human immune cells detailed on bioarxiv.
Also be sure to check out the great write-up by the ETH Zurich News team and wonderful Twitter posts by Jarrod Shilts and Eric Topol.