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Phil Kitchen

@kitchenphil.bsky.social

598 followers 461 following 12 posts

BBSRC Discovery fellow at @AstonUniversity. I use and develop molecular and biophysical tools to study aquaporins, glia, and CNS barriers. Late-diagnosed autistic. he/him

Posts Replies Media

Reposted by Phil Kitchen

Naomi Pollock @naomilpollock.bsky.social · 18/03/2025

We're also collaborating with a colleague at Harwell to use neutrons to investigate lipid exchange between membranes. Lots of protein biochemistry and biophysics. Get in touch if that's your idea of a good time!

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Reposted by Phil Kitchen

Naomi Pollock @naomilpollock.bsky.social · 18/03/2025

A reminder that the new institute for membrane science at Aston University has openings for PhD students. I'm offering a project together with @kitchenphil.bsky.social using polymer/lipid particles to understand lipid-protein interactions with membranes. www.findaphd.com/phds/project...

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Phil Kitchen @kitchenphil.bsky.social · 06/12/2024

Could you add me please?

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Phil Kitchen @kitchenphil.bsky.social · 05/12/2024

Lucas is now on bluesky at @ungerlucas.bsky.social

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Phil Kitchen @kitchenphil.bsky.social · 05/12/2024

This is (bluesky-less) Lucas Unger's first manuscript from his PhD work, and a big team effort involving members of #TeamAQP across the world. We are keen to get feedback on our study, and urge caution to researchers using AER-270 or TGN-020 in their work!

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Phil Kitchen @kitchenphil.bsky.social · 05/12/2024

TGN-020 appears to be an allosteric modulator of adenosine receptors, and both compounds modulated mTOR signalling in astrocytes (in opposite directions). These off-target effects mean that existing literature on effects of AER-270 and TGN-020 in in vivo models should be re-evaluated.

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Phil Kitchen @kitchenphil.bsky.social · 05/12/2024

We further report a variety of off-target effects of these compounds. AER-270 inhibited carbonic anhydrase and NF-kB signalling via IKKB with downstream effects on AQP4 gene expression.

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Phil Kitchen @kitchenphil.bsky.social · 05/12/2024

We conclude that the Xenopus assay is susceptible to false positive hits. Using a proteomics-based target identification method, we found 30 common targets of TGN-020 and AER-270 in Xenopus oocytes which could plausibly explain this.

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Phil Kitchen @kitchenphil.bsky.social · 05/12/2024

There are several other examples of “aquaporin-4 inhibitors” in the literature that appear to inhibit aquaporin-4 in the Xenopus assay but not in any other assay system, including acetazolamide, and various antiepileptics and loop diuretics.

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Phil Kitchen @kitchenphil.bsky.social · 05/12/2024

We then went back to the “gold standard” Xenopus laevis oocyte swelling assay and found apparent inhibitory effects, consistent with the existing literature.

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Phil Kitchen @kitchenphil.bsky.social · 05/12/2024

We tested AER-270 and TGN-020 using recombinant AQP4 protein reconstituted into proteoliposomes and again found no inhibitory effect.

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Phil Kitchen @kitchenphil.bsky.social · 05/12/2024

We initially became interested in TGN-020 and AER-270 as positive controls in a screen for novel aquaporin-4 modulators. To our surprise, they were not functional in assays using mammalian cell lines overexpressing aquaporin-4, nor in primary astrocytes.

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Phil Kitchen @kitchenphil.bsky.social · 05/12/2024

Our lab's first Biorxiv deposition is live! We show that two commercially-available "aquaporin-4 inhibitors" do not inhibit aquaporin-4 as previously described. www.biorxiv.org/content/10.1...

biorxiv.org

AER-270 and TGN-020 are not aquaporin-4 water channel blockers

Aquaporin-4 (AQP4) is the most abundant water channel protein in the brain. It controls water homeostasis, facilitates glymphatic function and is a drug target for brain edema following injury or stro...

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Phil Kitchen @kitchenphil.bsky.social · 17/11/2024

🌟PhD Opportunity in membrane biophysics!🌟 Fully-funded 4 year PhD studentship at @AstonAIME with @NaomiLPollock1 using neutron scattering at @isisneutronmuon to study lipid interactions with membrane proteins. Apply now: www.aston.ac.uk/graduate-sch... #PhDOpportunity #Biophysics

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