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Reposted by Azadeh Shahsavar

Kien-Lam Ung @unglam.bsky.social · May 21

🚨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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Reposted by Azadeh Shahsavar

The Interactive Fly @interactivefly.bsky.social · May 9

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/...

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...

onlinelibrary.wiley.com

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Azadeh Shahsavar @azadeh-shahsavar.bsky.social · Apr 26

Thank you, Aritz 🤗

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Azadeh Shahsavar @azadeh-shahsavar.bsky.social · Apr 25

Cheers! ☺️

Azadeh Shahsavar @azadeh-shahsavar.bsky.social · Apr 24

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

Azadeh Shahsavar @azadeh-shahsavar.bsky.social · Apr 24

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.

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Azadeh Shahsavar @azadeh-shahsavar.bsky.social · Apr 24

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

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Azadeh Shahsavar @azadeh-shahsavar.bsky.social · Apr 24

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.

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Azadeh Shahsavar @azadeh-shahsavar.bsky.social · Apr 24

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.

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Azadeh Shahsavar @azadeh-shahsavar.bsky.social · Apr 24

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...

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...

www.biorxiv.org

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Azadeh Shahsavar @azadeh-shahsavar.bsky.social · Apr 24

Congratulations!! SLC6 transporters rule!

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Azadeh Shahsavar @azadeh-shahsavar.bsky.social · Mar 29

Thank you, Nadia! ☺️

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Azadeh Shahsavar @azadeh-shahsavar.bsky.social · Mar 29

Thanks Stephan!

Azadeh Shahsavar @azadeh-shahsavar.bsky.social · Mar 29

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

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Azadeh Shahsavar @azadeh-shahsavar.bsky.social · Mar 29

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

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Azadeh Shahsavar @azadeh-shahsavar.bsky.social · Mar 29

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.

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Azadeh Shahsavar @azadeh-shahsavar.bsky.social · Mar 29

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...

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...

www.biorxiv.org

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Azadeh Shahsavar @azadeh-shahsavar.bsky.social · Mar 20

Happy Nowruz! Happy first day of spring 🌺

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Azadeh Shahsavar @azadeh-shahsavar.bsky.social · Mar 14

I mean… just saw this:

Azadeh Shahsavar @azadeh-shahsavar.bsky.social · Mar 12

Thank you!

Azadeh Shahsavar @azadeh-shahsavar.bsky.social · Mar 11

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

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Azadeh Shahsavar @azadeh-shahsavar.bsky.social · Mar 9

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...

ORCID

orcid.org

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Azadeh Shahsavar @azadeh-shahsavar.bsky.social · Mar 4

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

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Azadeh Shahsavar @azadeh-shahsavar.bsky.social · Mar 3

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

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Azadeh Shahsavar @azadeh-shahsavar.bsky.social · Feb 11

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

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