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Alejandra Tomas @tomaslab-imperial.bsky.social · 04/02/2026

Thanks to all the coauthors, particularly Denise Wootten and Giuseppe Deganutti for the cryo-EM and MD simulations, and the first author, former PhD student Liliane El Eid

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Alejandra Tomas @tomaslab-imperial.bsky.social · 04/02/2026

Ongoing, unpublished work further suggests behavioural alterations and changes in body fat distribution in the A316T variant mice, which we are now actively investigating.

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Alejandra Tomas @tomaslab-imperial.bsky.social · 04/02/2026

characterised by increased microsteatosis. This was linked to reduced glucagon secretion, plasma aminoacidosis, and α‑cell hyperplasia, highlighting that constitutive GLP‑1R activation is not universally beneficial.

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Alejandra Tomas @tomaslab-imperial.bsky.social · 04/02/2026

which led to reduced surface expression of the variant receptor, explaining the heightened desensitisation associated with this constitutively active receptor variant. Unexpectedly, when challenged with a high‑fat diet, A316T mice developed an adverse hepatic phenotype...

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Alejandra Tomas @tomaslab-imperial.bsky.social · 04/02/2026

particularly ligands that are not biased away from β‑arrestin recruitment. This pointed to increased basal signalling and enhanced receptor desensitisation effects. Mechanistic studies in islets from these mice, as well as in rat and human β‑cell models, revealed increased lysosomal trafficking...

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Alejandra Tomas @tomaslab-imperial.bsky.social · 04/02/2026

In parallel, we resolved the cryo‑EM structure of GLP‑1R A316T variant, providing structural insight into its altered signalling behaviour. Despite improved glucose tolerance and reduced weight gain under a high fat diet, A316T mice were largely unresponsive to pharmacological incretin therapies,

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Alejandra Tomas @tomaslab-imperial.bsky.social · 04/02/2026

I am delighted to report that our latest paper has now been published in Science Advances: www.science.org/doi/10.1126/... In this study, we generated and characterised a humanised GLP‑1R mouse model carrying the gain‑of‑function A316T variant using CRISPR/Cas9 knock‑in technology.

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Alejandra Tomas @tomaslab-imperial.bsky.social · 16/01/2026

Our review on GLP-1R signal compartmentalization is now out in JCI, where we discuss current evidence for the existence of GLP-1R–cAMP–PKA signalosomes at different subcellular locations and the complexity of the GLP-1R spatiotemporal signaling architecture: www.jci.org/articles/vie...

jci.org

JCI - Signaling architecture of the glucagon-like peptide-1 receptor

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Alejandra Tomas @tomaslab-imperial.bsky.social · 31/08/2025

Many thanks David, here is to many more collaborations on our favourite receptors and cells!

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Alejandra Tomas @tomaslab-imperial.bsky.social · 31/08/2025

I’m delighted to share that I have been promoted to Professor of Cell Biology at Imperial College London. I am deeply grateful to those who have supported me along the way, through the many ups and downs that led to this point.

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Alejandra Tomas @tomaslab-imperial.bsky.social · 20/08/2025

And a new paper from our group now published in DOM on a novel dual GLP-1R/GIPR agonist with improved action in vivo doi.org/10.1111/dom....

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Alejandra Tomas @tomaslab-imperial.bsky.social · 09/03/2025

Still time to apply to this Lectureship position in our Section. Deadline 25th March.

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Alejandra Tomas @tomaslab-imperial.bsky.social · 08/03/2025

Congratulations to Liliane ElEid who successfully passed her PhD viva yesterday! Here are some pictures of the post-viva celebrations. Many thanks to Prof David Hodson @daveyboyhod.bsky.social and Dr Bryn Owen for assessing her thesis and to David for his visit and Seminar.

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Alejandra Tomas @tomaslab-imperial.bsky.social · 15/02/2025

Are you interested in developing a research programme in cell biology of diabetes? Do you work in pancreatic islets and/or other metabolically relevant cells? We have a Lectureship post opening in our Section @imperialcollegeldn.bsky.social Apply by 25th March: www.imperial.ac.uk/jobs/search-...

imperial.ac.uk

Description

Please note that job descriptions are not exhaustive, and you may be asked to take on additional duties that align with the key responsibilities ment...

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Alejandra Tomas @tomaslab-imperial.bsky.social · 06/01/2025

Last few days to apply for a postdoc position in my lab

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Alejandra Tomas @tomaslab-imperial.bsky.social · 22/12/2024

Our collaboration with the talented Sarah Rouse now out in bioRxiv: "Human class B1 GPCR modulation by plasma membrane lipids" www.biorxiv.org/content/10.1...

biorxiv.org

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Alejandra Tomas @tomaslab-imperial.bsky.social · 20/12/2024

Still time to apply to this position! Application open until 15th Jan 2025.

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Alejandra Tomas @tomaslab-imperial.bsky.social · 08/12/2024

A postdoctoral position is available in my lab to study the subcellular organisation of signalling of the glucagon receptor family. For more information and to apply please click here: www.imperial.ac.uk/jobs/search-...

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