Here is the morph video summarizing some of the changes we found in a TRPC3 hypermorphic variant (Science Advances, Science Magazine)
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Functional and structural basis of a hypermorphic TRPC3 variant Structural snapshots capture an ataxia-linked overactive ion channel in its open state and reveal a druggable site for inhibition.

We are grateful to all the authors and collaborators who made this study possible. Special thanks to everyone in the Cordero-Morales and Vásquez laboratories (especially Briar Bell, Angela Jaramillo-Granda, and Luis Romero), as well as to our collaborators.

www.science.org/doi/10.1126/... (3/4)

Functional and structural basis of a hypermorphic TRPC3 variant Structural snapshots capture an ataxia-linked overactive ion channel in its open state and reveal a druggable site for inhibition.

Using electrophysiology, cryo-EM, molecular simulations, and in vivo models, we also identify a druggable inhibitory site that could guide future therapies for cerebellar ataxia.

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Functional and structural basis of a hypermorphic TRPC3 variant Structural snapshots capture an ataxia-linked overactive ion channel in its open state and reveal a druggable site for inhibition.

Excited to share our new paper in Science Advances @science.org

In this work, we uncover how a disease-linked TRPC3 mutation, together with a cerebellum-specific splice isoform, stabilizes the channel in an open state, drives Calcium overload, and promotes neurodegeneration. (1/4)

A great opportunity to bring trainees, exchange ideas, and connect across disciplines. Registration is open: www.grc.org/ion-channels...

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We have an outstanding speaker lineup, including Keynote Talks by Kenton Swartz, Nancy Carrasco, Miriam B. Goodman (@wormsense.bsky.social), and Francisco Bezanilla. Trailblazer Spotlights presented by Ed Twomey (@cryoet.bsky.social)and Theanne Griffith (@doctheagrif.bsky.social).

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Sudha (@chakrapanilab.bsky.social) and Julio (@cvlab.bsky.social) are organizing the 2026 Ion Channel Gordon Research Conference: Ion Channels Across Scales — Bridging Molecular Events to Physiological Outcomes, to be held at Mount Holyoke College, July 12–17, 2026.

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This work was a collaboration with Mat Baker (UTHealth Houston), the Chesler Lab @alexchesler.bsky.social (NIH), and the Sotomayor Lab (University of Chicago).

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4. The pore-distal, N-terminal blade is dispensable for mechanoactivation: the intermediate isoform is not only functional, but also inactivates more slowly than the long isoform.
5. The intermediate isoform induces larger membrane deformation than the long isoform.

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1. The longest isoform resembles a Mercedes-Benz steering wheel in top view.
2. The long and intermediate isoforms are semi-flattened and differ from the mammalian domes.
3. Multiple blade–cap contacts stabilize a “toggle-down” conformation.

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Briar and Angela (CV Lab) solved three structures from heavily spliced worm isoforms. Along the way —while solving the structures, characterizing their function, and evaluating effects on membrane curvature— we ran into several surprises:

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Structures of invertebrate PEZO-1 isoforms with a compact architecture and a dispensable pore-distal N-terminal blade PIEZO channels are mechanosensitive ion channels conserved from plants to humans, yet structures exist for only a few mammalian orthologs. We define t…

The Cordero Vásquez Lab is starting the year on a high wheel (see below) with our latest work on the C. elegans PIEZO channel: “Structures of invertebrate PEZO-1 isoforms with a compact architecture and a dispensable pore-distal N-terminal blade”: www.sciencedirect.com/science/arti...
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Thanks to our team members (Luis Romero, Manisha Bade, Sonia Paz-López) and collaborators (Elisa Carrillo, Vasanthi Jayaraman @frettinglab.bsky.social , Syed Hasan, William James Antonisamy, and Zahoor Shah) 6/6

Our results highlight cytoskeletal dysregulation as a key driver of ion channel and behavioral deficits, and suggest that actin-binding proteins may be targets to enhance motor coordination and spatial learning in AS. 5/6

currents in hippocampal neurons, and improves rotarod and T-maze performance in AS mice. 4/6

In Angelman syndrome (AS), disrupted F-actin affects mechanosensitive and glutamatergic signaling. We show that a first-in-class, selective cofilin inhibitor (SZ-3) stabilizes the actin cytoskeleton, increases cellular stiffness, restores PIEZO2 function in DRG neurons and glutamate-evoked 3/6

This Week in The Journal Mechanistic Insight into Angelman Syndrome Treatments Luis O. Romero, Manisha Bade, Elisa Carrillo, Sonia Paz-López, Syed A. M. Hasan et al. (see article e0965252025) People with Angelman syndrome...

It was nicely highlighted by Paige McKeon in “This Week in The Journal: www.jneurosci.org/content/45/4... 2/6

Cofilin Inhibition Ameliorates PIEZO2 and AMPA Dysfunction in a Mouse Model of Angelman Syndrome Angelman syndrome (AS) is a neurogenetic disorder characterized by motor coordination and cognitive deficits. In AS, hippocampal neurons show reduced filamentous (F-)actin, a decrease we also reported...

Our new Journal of Neuroscience paper "Cofilin Inhibition Ameliorates PIEZO2 and AMPA Dysfunction in a Mouse Model of Angelman Syndrome (AS)” is out: www.jneurosci.org/content/45/4... 1/6

Great series and this game7 was one of the greatest games Ive ever seen! Congrats Dodgers! Yamamoto has to be MVP of this series.

(TMC, the world’s largest medical complex). 2/2

The Department of Biochemistry and Molecular Biology at UTHealth Houston has an open search for a tenure-track faculty position. If you are ready (or know someone that is) to start looking for positions, this will be a great opportunity to join the Texas Medical Center. See flyer below. 1/2

The Nobel Peace Committee sent a clear message to someone else in awarding the Prize to Ms. Machado:
”But democracy is also in retreat internationally. Democracy – understood as the right to freely express one’s opinion, …is the foundation of peace both within countries and between countries.” 👏

Nobel Peace Prize 2025 The Nobel Peace Prize 2025 was awarded to Maria Corina Machado "for her tireless work promoting democratic rights for the people of Venezuela and for her struggle to achieve a just and peaceful transi...

“The Nobel Peace Prize for 2025 goes to a brave and committed champion of peace – to a woman who keeps the flame of democracy burning amid a growing darkness.”

www.nobelprize.org/prizes/peace...

This study was a collaborative effort across multiple groups, led by our first graduate student, Dr.
Luis Octavio Romero, in partnership with graduate student Manisha Bade. 3/3

PIEZO1 is abnormally overactive in sickle red blood cells (humans and mice). In mice, an EPA-enriched diet normalized PIEZO1 and reduced hemolysis, hypoxia-induced sickling, and downstream inflammation, suggesting a potential dietary strategy to support people living with sickle cell disease. 2/3

Enhanced PIEZO1 function contributes to the pathogenesis of sickle cell disease | PNAS Sickle cell disease (SCD), an inherited blood disorder caused by a mutation in the β-globin gene, is characterized by sickle erythrocytes that are ...

Our new PNAS paper "Enhanced PIEZO1 function contributes to the pathogenesis of sickle cell disease" is out: www.pnas.org/doi/10.1073/... 1/3

UC Davis researchers honored by McKnight and Howard Hughes Medical Institute UC Davis faculty Sergey Stavisky, Theanne Griffith and Elisa Zhang receive prestigious early-career recognition from McKnight Endowment Fund and the Howard Hughes Medical Institute.

I’m so honored to be selected as both a 2025 McKnight Scholar and 2025 HHMI Freeman Hrabowski Scholar. And I couldn’t be prouder to share these honors with awesome @ucdavis.bsky.social colleagues 💙💛💙💛

health.ucdavis.edu/news/headlin...

Such fantastic news! Congratulations!

Nobel laureate on how Trump's cuts are hurting science Neuroscientist, biologist and 2021 Nobel Prize winner Ardem Patapoutian joined Midday Edition to talk about how the Trump administration's effort to cut back on science spending is impacting researche...

I spoke with Jade Hindmon, host of @kpbssandiego.bsky.social Midday Edition, about the consequences of the current administration’s cuts to science funding. Please share to help spread the word and raise awareness.
www.kpbs.org/podcasts/kpb...