Our lab in the news:

https://vancouversun.com/news/ubc-researchers-discover-why-cholesterol-lowering-statins-harm-muscles-heres-why-that-matters

https://www.news-medical.net/news/20251126/UBC-researchers-reveal-how-statins-trigger-muscle-damage.aspx

https://www.sciencenewstoday.org/scientists-uncover-the-secret-behind-statin-side-effects-and-a-path-to-safer-drugs

​https://news.ubc.ca/2025/11/ubc-statins-muscles-research/

Cholesterol and Muscle-related side effects: how statins affect a critical muscle ion channel

​Statins represented the most prescribed class of drugs in westernized countries. Intended to lower blood plasma cholesterol, many patients report muscle-related side effects and in some cases statins can cause complete muscle breakdown, resulting in kidney failure that can be fatal. Here we show that atorvastatin, the active molecule in Lipitor, directly engages a large protein - RyR1 - that is critical in muscle function. Under normal conditions, electrical stimulation of the muscle cells results in activation of RyR1, which then releases calcium ions from a compartment known as the Sarcoplasmic Reticulum. This event then results in muscle contraction. Using cryo-electron microscopy, we show that multiple atorvastatin molecules directly bind to a critical site of RyR1, causing it to open. The resulting sustained leak of calcium can then affect muscle function and be toxic in excess.

Comparing the binding mode of atorvastatin to RyR1 compared to an enzyme involved in cholesterol synthesis (HMG-CoA-reductase) provides direct clues on how to modify the statins do disrupt RyR1 binding while retaining an inhibitory effect on cholesterol production.
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https://www.nature.com/articles/s41467-025-66522-0

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Elucidating the elusive Type 3 Ryanodine Receptor.
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The Type 3 Ryanodine Receptor (RyR3) is a large ER-resident calcium channel that plays a critical role various tissues, including neurons where it is involved in learning and memory. We solved high-resolution cryo-EM structures of RyR3 in different conformational states. RyR3 has unique functional properties leading to a high gain of calcium release. We identified binding sites for chloride and ATP in the N-terminal region and an altered interface with an auxiliary protein known as FKBP12/12.6. Our work suggests a direct link with epileptic encephalopathy, likely caused by mutations in RyR3.

https://www.nature.com/articles/s41467-024-52998-9
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David vs Goliath: How a small scorpion peptide takes control of a ~20,000-residue membrane protein...

​Pandinus imperator, a.k.a. the emperor scorpion, produces a venomous peptide known as imperacalcin. This peptide can cross the plasma membrane and gain access to an intracellular target: the Ryanodine Receptor. Our cryo-EM study shows imperacalcin (green) binding adjacent to the transmembrane region of this ion channel, where it causes a partial reduction in ionic flow, causing a 'subconductance', easily visible in single channel electrophysiology recordings ('S').  It also holds the channel in an open conformation and breaks the 4-fold symmetry. 

https://www.science.org/doi/10.1126/sciadv.adf4936