Azadeh Shahsavar

🚨My new team at @ipbstoulouse.bsky.social in France currently have an open, fully-funded PhD position 🧑‍🔬👩‍🔬to study membrane proteins & transporters of therapeutic interest using cryo-EM & biophysics.🧊🔬🦠

#StructuralBiology #MicroSky

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Cryo‐EM structure of the dopamine transporter with a novel atypical non‐competitive inhibitor bound to the orthosteric site Atypical inhibitors of dopamine transporter lack the rewarding effects of psychostimulants and offer a promising strategy for the treatment of drug use disorders. In this study, we present the cryo-e...

Pedersen, C. N., Yang, F., Ita, S., ..., Mortensen, O. V., Nissen, P., Shahsavar, A. (2024). Cryo-EM structure of the dopamine transporter with a novel atypical non-competitive inhibitor bound to the orthosteric site. J Neurochem, onlinelibrary.wiley.com/doi/10.1111/...

Thank you, Aritz 🤗

Cheers! ☺️

We are grateful for the support from:
@lundbeckfonden.bsky.social
@novo-nordisk.bsky.social
@ NIDA

This interdisciplinary research represents nothing less than a tour de force by Ryan P. Cantwell Chater, and a great collaborative effort between the labs of
Robert Vandenberg, Christopher Cioffi, Megan O'mara, Mike Michaelides, Sarasa Mohammadi and myself.

Our findings provide proof-of-concept for the rational design of GlyT2 inhibitors and a clear avenue for novel treatments of chronic neuropathic pain.

We show that RPI-GLYT2-82 is efficacious at alleviating pain in mouse models of neuropathic pain with no mechanism-based side effects tested at doses up to 5 times the maximal analgesic dose, or addiction liability at up to 3 times the maximal analgesic dose.

We have determined the first #cryoEM structures of human GlyT2 bound to a potent pseudo-irreversible inhibitor (ORG25543) that failed in pre-clinical studies, a novel and reversible inhibitor (RPI-GLYT2-82), and in the substrate-free state.

Structural insights into allosteric mechanism of glycine transporter-mediated analgesia Chronic neuropathic pain, caused by nerve damage or disease, affects 10% of the population with rising incidence. The burden is exacerbated by ineffective treatments and overreliance on opioids. Neuro...

Beyond excited to present our study on the glycine transporter #GlyT2, a promising #non-opioid target for the treatment of neuropathic pain.
@biorxivpreprint.bsky.social

www.biorxiv.org/content/10.1...

Congratulations!! SLC6 transporters rule!

Thank you, Nadia! ☺️

Thanks Stephan!

and the Core Facility for Integrated Microscopy – CFIM – funded by @novo-nordisk.bsky.social where we collected our cryo-EM data on the first batch of newly developed HexAuFoil grids from @quantifoil.bsky.social

Our study will facilitate structure-based design of improved selective inhibitors targeting GAT3 for more efficient treatment of epilepsy and a range of other neurological disorders. We are grateful for the support from
@lundbeckfonden.bsky.social
@novo-nordisk.bsky.social
@DFF_raad

Our inhibitor-bound inward-open GAT3 reveals the binding mode of SR-THAP and the structural determinants of selectivity. Our GABA-bound inward-occluded GAT3 reveals ion coordination and substrate recognition network with exciting distinction to that previously observed for the GAT1 subtype.

Structural basis for selective inhibition of human GABA transporter GAT3 The astrocytic γ-aminobutyric acid (GABA) transporter, GAT3, is essential for terminating GABAergic signalling in the central nervous system. Selective inhibition of GAT3 offers a potential strategy f...

We are excited to present the first #cryoEM structures of human GABA transporter 3 – GAT3 – bound to an in-house selective inhibitor, SR-THAP, to substrate GABA, and in the substrate-free state!
@biorxivpreprint.bsky.social
www.biorxiv.org/content/10.1...

Happy Nowruz! Happy first day of spring 🌺

I mean… just saw this:

Thank you!

How is this not illegal?!! 🤯 I can’t understand how/why canceling an ongoing grant is even possible 😮‍💨

Hi Erik! Would you add me too? Structural biologist by training, interested in effective targeting of membrane transporters in diseases. ORCID: orcid.org/0000-0001-54...

Oh, wow, completely had forgotten about these safety tests. I’ll get to do it soon hopefully at Petra III - starting a SSX project 🥲

This looks so much better (safer) than what we use..

I had such an amazing day, Nadia! Thanks for having me 🤗

📣 It’s my great pleasure to host @azadeh-shahsavar.bsky.social from the University of Copenhagen, in our department @pasteur.fr tomorrow.
Very much looking forward to her talk 👇

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Could you add me, Ute? Cheers!