Alejandro Llorente, Ph.D.
@llorentealejandro.bsky.social
18 followers 36 following 12 posts
Postdoctoral fellow at Columbia University. Working on structural biology and protein engineering at the laboratory of Dr. Oliver Clark
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llorentealejandro.bsky.social
8/9 ✅My work details how we successfully engineered a version of human NIS that transports as much ReO₄⁻ as WT-NIS, and it doesn’t transport I⁻. We created a molecular tool that could be used to kill cancer cells while shielding the thyroid gland!
llorentealejandro.bsky.social
7/9 Fun fact! The protective non-radioactive I⁻ works just like the famous iodide pills given after a nuclear event like Chernobyl—it floods/saturates WT-NIS in the thyroid, protecting us from the radioactive I⁻ isotopes resulting from the disaster.
a cartoon of homer simpson with a green light coming out of his chest
ALT: a cartoon of homer simpson with a green light coming out of his chest
media.tenor.com
llorentealejandro.bsky.social
6/9 🛠️ An engineered-NIS molecule that only transports ReO₄⁻ opens up a new therapeutic strategy:

1. Introduce the engineered-NIS into tumor cells.

2. Treat with radioactive ReO₄⁻ to kill the tumoral cells.

3. Protect healthy thyroid by giving the patient non-radioactive I⁻! 🛡
llorentealejandro.bsky.social
5/9 💡 But what if we could be more specific? NIS doesn’t just transport I⁻; it can also transport other, “similar” molecules called oxyanions, like perrhenate (ReO₄⁻).

This led to our key question: could we engineer a version of NIS that only transports ReO₄⁻?
llorentealejandro.bsky.social
4/9🎯 For 30 years, Dr. Carrasco has dreamed of using NIS as a "trojan horse" to treat cancer.

The idea? Introduce NIS into non-thyroidal tumoral cells and give the patient radioactive iodide to kill them.

The problem? You'd also destroy the patient's healthy thyroid gland. ⚠️
llorentealejandro.bsky.social
3/9 🧬 The effectiveness of this treatment is all due to one protein: the Na+/I⁻ Symporter (NIS), the only transporter that mediates active transport of iodide (I⁻) into thyroid cells. The groundwork for understanding NIS was laid by my mentor, Dr. Nancy Carrasco, who first cloned its cDNA in 1996! 🙌
llorentealejandro.bsky.social
2/9 📈Did you know thyroid cancer has the highest 5-year survival rate? That's thanks to the highly effective radioiodide (¹³¹I⁻) therapy, a treatment that's been a game-changer since 1946!
seer.cancer.gov/statfacts/ht...
llorentealejandro.bsky.social
1/9 🚀 Big news! As a result of 5 years of my PhD, building on a 30-year dream of my PI Dr. Nancy Carrasco, we think we've found a new way to treat cancer! We’ve released our preprint & I'm so excited to share this story! 🧵
www.biorxiv.org/content/10.1...
#Science #proteinengineering #proteindesing
Engineering substrate selectivity in the human sodium/iodide symporter (NIS)
Iodide (I-) uptake mediated by the Na+/I- symporter (NIS) is the first step in the biosynthesis of the thyroid hormones, of which I- is an essential constituent. NIS couples the inward transport of I-...
www.biorxiv.org
Reposted by Alejandro Llorente, Ph.D.
olibclarke.bsky.social
This one is a bit of a departure from the usual and definitely a work in progress!

We found that by using ab initio reconstruction at very high res, in very small steps, we could crack some small structures that had eluded us - e.g. 39kDa iPKAc (EMPIAR-10252), below.

Read on for details... 1/x
Reposted by Alejandro Llorente, Ph.D.
biorxiv-biophys.bsky.social
High-resolution ab initio reconstruction enables cryo-EM structure determination of small particles https://www.biorxiv.org/content/10.1101/2025.09.08.674935v1
llorentealejandro.bsky.social
Congratulations, Oli and Huan! This is such hard work—I’m really excited to see it out now. I can’t wait to see if some kind of protein engineering can take advantage of the arrangement of the protomers’ C-termini.
Reposted by Alejandro Llorente, Ph.D.
olibclarke.bsky.social
I know there are more important things to worry about right now... but it really pisses me off coming across things like this in the literature.

Nominally 4.8 Å map... check out Fig S1 😬

(also check out any other #cryoem paper by same group, ~all in BBRC)

www.sciencedirect.com/science/arti...
llorentealejandro.bsky.social
Hi all, I am happy to be now in a much more inclusive place ❤️🏳️‍🌈🔬